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Bibliography on: Fecal Transplantation

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ESP: PubMed Auto Bibliography 19 Apr 2021 at 01:33 Created: 

Fecal Transplantation

Fecal Transplantion is a procedure in which fecal matter is collected from a tested donor, mixed with a saline or other solution, strained, and placed in a patient, by colonoscopy, endoscopy, sigmoidoscopy, or enema. The theory behind the procedure is that a normal gut microbial ecosystem is required for good health and that sometimes a benefucuial ecosystem can be destroyed, perhaps by antibiotics, allowing other bacteria, specifically Clostridium difficile to over-populate the colon, causing debilitating, sometimes fatal diarrhea. C. diff. is on the rise throughout the world. The CDC reports that approximately 347,000 people in the U.S. alone were diagnosed with this infection in 2012. Of those, at least 14,000 died. Fecal transplant has also had promising results with many other digestive or auto-immune diseases, including Irritable Bowel Syndrome, Crohn's Disease, and Ulcerative Colitis. It has also been used around the world to treat other conditions, although more research in other areas is needed. Fecal transplant was first documented in 4th century China, where the treatment was known as yellow soup.

Created with PubMed® Query: "(fecal OR faecal) (transplant OR transplantation)" OR "fecal microbiota transplant" NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)


RevDate: 2021-04-17

Pomares Bascuñana RÁ, Veses V, CC Sheth (2021)

Effectiveness of fecal microbiota transplant for the treatment of Clostridioides difficile diarrhea: A systematic review and meta-analysis.

Letters in applied microbiology [Epub ahead of print].

Clostridioides difficile is a major cause of health-care related infections and antibiotic-associated diarrhea. High recurrence rates following antibiotic treatment, along with the emergence of hypervirulent and multidrug resistant ribotypes makes essential the development of safe, effective, novel therapies for the treatment of C. difficile infections. The primary outcome evaluated in this meta-analysis was the effectiveness of fecal microbiota transplantation (FMT). Secondary outcomes were the proportion of patients suffering adverse effects along with the most effective administration route. The mean treatment effectiveness was 82% (95% CI: 75-89). Overall, patients receiving FMT via colonoscopy experienced more adverse effects than patients whom received enema, or oral capsules (71.6 % versus 40.2 %, and 35.3% respectively). Comparing administration of FMT by colonoscopy versus enema resulted in a Hedges' g of -0.74 (95% CI of -0.9 - -0.58), indicating a slight advantage in favor of colonoscopy. The comparison between colonoscopy and capsule returned a Hedges' g of 0.44 (95% CI of 0.20 - 0.69), indicating that delivery of the FMT by capsule was statistically significantly more effective. FMT provides an effective and safe treatment for C. difficile diarrhea. Further research into the efficacy of different preparation protocols is needed.

RevDate: 2021-04-17

Li X, Su C, Jiang Z, et al (2021)

Berberine attenuates choline-induced atherosclerosis by inhibiting trimethylamine and trimethylamine-N-oxide production via manipulating the gut microbiome.

NPJ biofilms and microbiomes, 7(1):36.

Trimethylamine-N-oxide (TMAO), a derivative from the gut microbiota metabolite trimethylamine (TMA), has been identified to be an independent risk factor for promoting atherosclerosis. Evidences suggest that berberine (BBR) could be used to treat obesity, diabetes and atherosclerosis, however, its mechanism is not clear mainly because of its poor oral bioavailability. Here, we show that BBR attenuated TMA/TMAO production in the C57BL/6J and ApoE KO mice fed with choline-supplemented chow diet, and mitigated atherosclerotic lesion areas in ApoE KO mice. Inhibition of TMA/TMAO production by BBR-modulated gut microbiota was proved by a single-dose administration of d9-choline in vivo. Metagenomic analysis of cecal contents demonstrated that BBR altered gut microbiota composition, microbiome functionality, and cutC/cntA gene abundance. Furthermore, BBR was shown to inhibit choline-to-TMA conversion in TMA-producing bacteria in vitro and in gut microbial consortium from fecal samples of choline-fed mice and human volunteers, and the result was confirmed by transplantation of TMA-producing bacteria in mice. These results offer new insights into the mechanisms responsible for the anti-atherosclerosis effects of BBR, which inhibits commensal microbial TMA production via gut microbiota remodeling.

RevDate: 2021-04-17

Albuhairi S, R Rachid (2021)

Biologics and Novel Therapies for Food Allergy.

Immunology and allergy clinics of North America, 41(2):271-283.

Food allergy is a significant public health burden affecting around 10% of adults and 8% of children. Although the first peanut oral immunotherapy product received Food and Drug Administration approval in 2020, there is still an unmet need for more effective therapeutic options that minimize the risk of anaphylaxis, nutritional deficiencies, and patient's quality of life. Biologics are promising modalities, as they may improve compliance, target multiple food allergies, and treat other concomitant atopic diseases. Although omalizumab has been evaluated extensively, most biologics are more novel and have broader immunologic impact. Careful evaluation of their safety profile should therefore be conducted.

RevDate: 2021-04-15

Wang Q, Luo Y, Chaudhuri KR, et al (2021)

The role of gut dysbiosis in Parkinson's disease: mechanistic insights andtherapeutic options.

Brain : a journal of neurology pii:6226389 [Epub ahead of print].

Parkinson's disease is a common neurodegenerative disease in which gastrointestinal symptoms may appear prior to motor symptoms. The gut microbiota of patients with Parkinson's disease shows unique changes, which may be used as early biomarkers of disease. Alteration in gut microbiota composition may be related to the cause or effect of motor or non-motor symptoms, but the specific pathogenic mechanisms are unclear. The gut microbiota and its metabolites have been suggested to be involved in the pathogenesis of Parkinson's disease by regulating neuroinflammation, barrier function and neurotransmitter activity. There is bidirectional communication between the enteric nervous system and the central nervous system, and the microbiota-gut-brain axis may provide a pathway for the transmission of α-synuclein. We highlight recent discoveries and alterations of the gut microbiota in Parkinson's disease, and highlight current mechanistic insights on the microbiota-gut-brain axis in disease pathophysiology. We discuss the interactions between production and transmission of α-synuclein and gut inflammation and neuroinflammation. In addition, we also draw attention to diet modification, use of probiotics and prebiotics and fecal microbiota transplantation as potential therapeutic approaches that may lead to a new treatment paradigm for Parkinson's disease.

RevDate: 2021-04-14

Ballif A, Gerber S, Carrez L, et al (2021)

[Fecal microbiota transplantation: from the evidence to the realty of the field].

Revue medicale suisse, 17(734):726-731.

In clinical practice, fecal microbiota transplantation (FMT) has been established as an unparalleled therapy to date for multiple recurrent Clostridioides difficile infections (CDI). The implementation of the FMT in practice requires a significant investment to meet legal, security and financial requirements. Research on the microbiota is booming and multiple investigations on FMT in indications other than CDI are ongoing.

RevDate: 2021-04-14

Cappetto CM (2021)

Successful use of early, repeat fecal microbiota transplantation for initial treatment of severe, refractory Clostridioides difficile colitis.

American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists pii:6225235 [Epub ahead of print].

DISCLAIMER: In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

PURPOSE: There is a paucity of literature surrounding the use of early fecal microbiota transplantation (FMT) for patients presenting with an initial episode of severe, refractory Clostridioides difficile infection (CDI). Information on optimal antibiotic dosing and therapy duration surrounding FMT during an acute, initial episode of CDI is also limited. Described here is a case of successful treatment of CDI after 4 FMTs during an acute, initial episode of severe, refractory Clostridioides difficile colitis.

SUMMARY: A 69-year-old community-dwelling, Caucasian male presented after 48 hours of vomiting and diarrhea. A stool sample tested positive via stool sample by both polymerase chain reaction and enzme-linked immunosorbent assays for Clostridioides difficile. The patient was treated with several days of oral and rectal vancomycin therapy in addition to intravenous metronidazole, but those treatments failed. His clinical and nutrition status deteriorated over the course of several days until salvage therapy was ordered, with administration of 1 inpatient nasogastric FMT and 1 inpatient colonoscopic FMT followed by outpatient colonoscopic FMTs on 2 consecutive days within 2 weeks of hospital discharge.

CONCLUSION: This case suggests a role for early, repeat FMT during an initial presentation of a severe Clostridioides difficile colitis episode refractory to pharmacologic antimicrobial therapy. It also adds to emerging literature regarding the timing of antibiotic cessation surrounding FMT.

RevDate: 2021-04-12

Monaghan TM, Seekatz AM, Markham NO, et al (2021)

Fecal microbiota transplantation for recurrent Clostridioides difficile infection associates with functional alterations in circulating microRNAs.

Gastroenterology pii:S0016-5085(21)00577-1 [Epub ahead of print].

BACKGROUND AND AIMS: The molecular mechanisms underlying successful fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (rCDI) remain poorly understood. The primary objective of this study was to characterize alterations in microRNAs (miRs) following FMT for rCDI.

METHODS: Sera from two prospective multicentre randomized controlled trials were analyzed for miRNA levels using the Nanostring nCounter platform and quantitative RT-PCR. Additionally, rCDI-FMT and toxin-treated animals and ex vivo human colonoids were employed to compare intestinal tissue and circulating miRNAs. miRNA inflammatory gene targets in colonic epithelial and peripheral blood mononuclear cells were evaluated by qPCR and 3'UTR reporter assays. Colonic epithelial cells were employed for mechanistic, cytoskeleton, cell growth and apoptosis studies.

RESULTS: miRNA profiling revealed upregulation of 64 circulating miRNAs 4- and 12-weeks following FMT compared to screening, of which the top 6 were validated in the discovery cohort by RT-qPCR. In a murine model of relapsing-CDI, RT-qPCR analyses of sera and cecal RNA extracts demonstrated suppression of these miRNAs, an effect reversed by FMT. In mouse colon and human colonoids, TcdB mediated the suppressive effects of CDI on miRNAs. CDI dysregulated Drosha, an effect reversed by FMT. Correlation analyses, qPCR and 3'UTR reporter assays revealed that miR-23a, miR-150, miR-26b, miR-28 target directly the 3'UTR of IL12B, IL18, FGF21 and TNFRSF9, respectively. miR-23a and miR-150 demonstrated cytoprotective effects against TcdB.

CONCLUSION: These results provide novel and provocative evidence that modulation of the gut microbiome via FMT induces alterations in circulating and intestinal tissue miRNAs. These findings contribute to a greater understanding of the molecular mechanisms underlying FMT and identify new potential targets for therapeutic intervention in rCDI.

RevDate: 2021-04-12

Madsen M, Kimer N, Bendtsen F, et al (2021)

Fecal microbiota transplantation in hepatic encephalopathy: a systematic review.

Scandinavian journal of gastroenterology [Epub ahead of print].

Hepatic encephalopathy (HE) is a reversible neurocognitive dysfunction that ranges in severity from subclinical alterations to coma. Patients with chronic liver disease are predisposed to HE due to metabolic failure and portosystemic shunting of toxins, of which ammonia is believed to be the main toxic chemical. Fecal microbiota transplantation (FMT) may reduce ammonia synthesis by altering the gut microbiota composition to a taxon low in urease, diminish uptake of ammonia by reestablishing the integrity of the intestinal barrier and increase ammonia clearance by improving liver function. In this systematic review, we summarize the insights of the current literature examining FMT as a treatment for HE.PubMed and EMBASE were searched on 08 February 2021 using the MeSH terms 'fecal microbiota transplantation & hepatic encephalopathy' and the abbreviations 'FMT & HE'.Eight studies fulfilled our inclusion criteria, comprising two randomized clinical trials, three case reports and three rodent studies. Thirty-nine patients with HE were treated with FMT. Thirty-nine rodents received FMT in laboratory tests. FMT improved neurocognitive test results in four human studies and two rodent studies. Microbiota originating from donors was found in human recipients one year post-FMT. Readmission of patients was lower after treatment with FMT compared to standard of care.FMT may improve neurocognitive function and reduce serious adverse events in patients with HE, but the studies conducted so far have been small and their long-term follow-up is limited. Large-scale, randomized and controlled trials are needed to validate and help standardize the clinical application of FMT in cases of HE.

RevDate: 2021-04-12

Björkqvist O, Rangel I, Serrander L, et al (2021)

Faecalibacterium prausnitzii increases following fecal microbiota transplantation in recurrent Clostridioides difficile infection.

PloS one, 16(4):e0249861 pii:PONE-D-21-02114.

OBJECTIVE: Fecal microbiota transplantation (FMT) is a highly effective treatment for Clostridioides difficile infection (CDI). However, the fecal transplant's causal components translating into clearance of the CDI are yet to be identified. The commensal bacteria Faecalibacterium prausnitzii may be of great interest in this context, since it is one of the most common species of the healthy gut microbiota and produces metabolites with anti-inflammatory properties. Although there is mounting evidence that F. prausnitzii is an important regulator of intestinal homeostasis, data about its role in CDI and FMT are relatively scarce.

METHODS: Stool samples from patients with recurrent CDI were collected to investigate the relative abundance of F. prausnitzii before and after FMT. Twenty-one patients provided fecal samples before the FMT procedure, at 2 weeks post-FMT, and at 2-4 months post-FMT. The relative abundance of F. prausnitzii was determined using quantitative polymerase chain reaction.

RESULTS: The abundance of F. prausnitzii was elevated in samples (N = 9) from donors compared to pre-FMT samples (N = 15) from patients (adjusted P<0.001). No significant difference in the abundance of F. prausnitzii between responders (N = 11) and non-responders (N = 4) was found before FMT (P = 0.85). In patients with CDI, the abundance of F. prausnitzii significantly increased in the 2 weeks post-FMT samples (N = 14) compared to the pre-FMT samples (N = 15, adjusted P<0.001). The increase persisted 2-4 months post-FMT (N = 15) compared to pre-FMT samples (N = 15) (adjusted P<0.001).

CONCLUSIONS: FMT increases the relative abundance of F. prausnitzii in patients with recurrent CDI, and this microbial shift remains several months later. The baseline abundance of F. prausnitzii in donors or recipients was not associated with future treatment response, although a true predictive capacity cannot be excluded because of the limited sample size. Further studies are needed to discern whether F. prausnitzii plays an active role in the resolution of CDI.

RevDate: 2021-04-11

Grigoryan Z, Shen MJ, Twardus SW, et al (2020)

Fecal microbiota transplantation: Uses, questions, and ethics.

Medicine in microecology, 6:.

Fecal microbiota transplantation (FMT) has rapidly grown in notoriety and popularity worldwide as a treatment for both recurrent and refractory C. difficile infection (CDI), as well as for a myriad of other indications, with varying levels of evidence to justify its use. At present, FMT use in the U.S. has not received marketing approval from the U.S. Food and Drug Administration (FDA), but is permitted under "enforcement discretion" for CDI not responding to standard therapy. Meanwhile, the rising interest in the gut microbiome throughout mainstream media has paved the way for "do-it-yourself" (DIY) adaptations of the procedure. This access and unregulated use, often outside any clinical supervision, has quickly outpaced the medical community's research and regulatory efforts. While some studies have been able to demonstrate the success of FMT in treating conditions other than CDI-studies on ulcerative colitis have been particularly promising-little is still known about the treatmen's mechanism of action or long-term side effects. Likewise, screening of donor stool is in its early stages in terms of protocol standardization. In this paper, we explore the regulatory and ethical concerns that arise from the need to balance access to a nascent but promising innovative treatment with the need for research into its efficacy, risk profile, and long-term impact.

RevDate: 2021-04-14

Fang S, Wu S, Ji L, et al (2021)

The combined therapy of fecal microbiota transplantation and laxatives for functional constipation in adults: A systematic review and meta-analysis of randomized controlled trials.

Medicine, 100(14):e25390.

OBJECTIVE: Functional constipation is a prevalent, burdensome gastrointestinal disorder whose treatment remains challenging. Combined therapy uniting multiple treatments may be promising. Fecal microbiota transplantation (FMT) which tends to be an etiological treatment has been increasingly investigated in its management. Meanwhile, laxatives are widely used to relieve constipation temporarily, but their overall efficacy is poor. Therefore, we performed meta-analyses of randomized controlled trials to evaluate the joint efficacy of FMT and laxatives in functional constipation.

METHODS: We performed a systematic literature search of 6 electronic databases as of August 11, 2020. Randomized controlled trial of FMT together with laxatives vs laxatives alone in functional constipation in adults were included. Two reviewers independently performed the screening, data extraction, and bias assessment. Dichotomous outcome data were synthesized by risk ratio, and measurement data by weighted mean difference (WMD).

RESULTS: A total of 1400 records were identified, of which 5 were eligible (409 patients). Overall, compared to laxatives alone, combined therapy of FMT and laxatives more significantly improved total effective rate (risk ratio: 1.35; 95% confidence interval [CI]: 1.14, 1.60; I2 = 13%), Bristol stool form scale score (WMD: 1.04; 95% CI: 0.57, 1.51; I2 = 76%), reduce Wexner score (WMD: -3.25; 95% CI: -5.58, -0.92; I2 = 92%), Knowles-Eccersley-Scott-Symptom (KESS) score (WMD: -5.65; 95% CI: -7.62, -3.69; I2 = 0%) and patient assessment of constipation quality of life score (WMD: -18.56; 95%; CI: -26.43, -10.68; I2 = 78%). No serious adverse events were reported. The majority of included studies had poor methodological quality.

CONCLUSION: Combined therapy of FMT and laxatives may be a reasonably effective and safe treatment for people with functional constipation. However, caution is needed with the interpretation of these data due to the small sample size, high heterogeneity, and low quality of the studies. Besides, we expect that more studies will be performed exploring the efficacy and safety of combined therapy for functional constipation.

RevDate: 2021-04-08

Dixon CE, Bedenice D, Restifo M, et al (2021)


Journal of zoo and wildlife medicine : official publication of the American Association of Zoo Veterinarians, 52(1):57-66.

This retrospective case series describes the clinicopathologic findings, diagnoses, treatment, and outcomes of 10 hand-reared newborn giraffe (Giraffa camelopardalis) calves admitted to a university teaching hospital for intensive care. Ten calves (five males, five females; nine reticulated giraffes [Giraffa camelopardalis reticulata], one Masai giraffe [G. c. tippelskirchi]), were admitted under 2 days of age. Inadequate transfer of passive immunity was suspected in 5 of 10 calves based on assessment of serum total solids and globulin values. These calves were treated with oral frozen bovine colostrum and/or intravenous hyperimmune bovine plasma. Diarrhea occurred in 6 of 10 calves and was managed with supportive care, fecal microbiota transplantation, and limiting milk intake (offering 10% body weight [BW] in milk per day, while feeding <2 L per meal at 2- to 4-hr intervals). Less common diagnoses included pneumonia (n = 3) and mycoplasma-associated septic arthritis (n = 1). Eight calves received systemic antimicrobial therapy. Hyperlactatemia (lactate > 5 mmol/L; n = 8) and hypercreatininemia (creatinine > 2.0 mg/dl, n = 7) were the most common presenting laboratory abnormalities, which resolved with intravenous fluid therapy. All neonatal giraffes survived to discharge after a median hospitalization of 9.5 days (range, 5-37 days) and were successfully hand-reared at their place of birth. In conclusion, neonatal giraffe calves can be intensively managed in a hospital environment. Diarrhea was a common clinical problem and can be related to feeding regimens. Intravenous hyperimmune bovine plasma infusion was well tolerated to manage failure of transfer of passive immunity in calves with inadequate colostrum administration. The current study supports that compromised neonatal giraffe calves may carry an excellent prognosis after early, intensive intervention.

RevDate: 2021-04-08

Park SY, GS Seo (2021)

Fecal Microbiota Transplantation: Is It Safe?.

Clinical endoscopy, 54(2):157-160.

Fecal microbiota transplantation (FMT) is an accepted procedure for the management of recurrent Clostridioides difficile infections. FMT is generally considered safe and well-tolerated - even in high-risk patients. Most short-term risks are mild and known to be associated with delivery methods. Long-term side effects have not been established, and no signs of harm have been found to date. However, causality for several microbiome-associated diseases has to be established. Even though FMT is generally considered safe with strict donor screening, serious adverse events have been recently associated with the FMT product from the stool bank, where screening for multi-drug resistant organisms is not included in protocols. Here, we discuss the adverse events associated with FMT and safety issues.

RevDate: 2021-04-07

Xiao L, Yan J, Yang T, et al (2021)

Fecal Microbiome Transplantation from Children with Autism Spectrum Disorder Modulates Tryptophan and Serotonergic Synapse Metabolism and Induces Altered Behaviors in Germ-Free Mice.

mSystems, 6(2):.

To determine the relationship of the gut microbiota and its metabolites with autism spectrum disorder (ASD)-like behaviors and preliminarily explore the potential molecular mechanisms, the fecal microbiota from donors with ASD and typically developing (TD) donors were transferred into germ-free (GF) mice to obtain ASD-FMT mice and TD-FMT mice, respectively. Behavioral tests were conducted on these mice after 3 weeks. 16S rRNA gene sequencing of the cecal contents and untargeted metabolomic analysis of the cecum, serum, and prefrontal cortex were performed. Untargeted metabolomics was also used to analyze fecal samples of TD and ASD children. Western blotting detected the protein expression levels of tryptophan hydroxylase 1 (TPH1), serotonin transporter (SERT), and serotonin 1A receptor (5-HT1AR) in the colon and TPH2, SERT, and 5-HT1AR in the prefrontal cortex of mice. ASD-FMT mice showed ASD-like behavior and a microbial community structure different from that of TD-FMT mice. Tryptophan and serotonin metabolisms were altered in both ASD and TD children and ASD-FMT and TD-FMT mice. Some microbiota may be related to tryptophan and serotonin metabolism. Compared with TD-FMT mice, ASD-FMT mice showed low SERT and 5-HT1AR and high TPH1 expression levels in the colon. In the prefrontal cortex, the expression levels of TPH2 and SERT were increased in the ASD-FMT group relative to the TD-FMT group. Therefore, the fecal microbiome of ASD children can lead to ASD-like behaviors, different microbial community structures, and altered tryptophan and serotonin metabolism in GF mice. These changes may be related to changes in some key proteins involved in the synthesis and transport of serotonin.IMPORTANCE The relationship between the gut microbiota and ASD is not yet fully understood. Numerous studies have focused on the differences in intestinal microbial and metabolism profiles between TD and ASD children. However, it is still not clear if these microbes and metabolites cause the development of ASD symptoms. Here, we collected fecal samples from TD and ASD children, transplanted them into GF mice, and found that the fecal microbiome of ASD children can lead to ASD-like behaviors, different microbial community structures, and altered tryptophan and serotonin metabolism in GF mice. We also demonstrated that tryptophan and serotonin metabolism was also altered in ASD and TD children. Together, these findings confirm that the microbiome from children with ASD may lead to ASD-like behavior of GF mice through metabolites, especially tryptophan and serotonin metabolism.

RevDate: 2021-04-11

Wang F, Song M, Lu X, et al (2021)

Gut microbes in gastrointestinal cancers.

Seminars in cancer biology pii:S1044-579X(21)00098-5 [Epub ahead of print].

Gut microbes (GMs), dominated by bacteria, play important roles in many physiological processes. The structures and functions of GMs are closely related to human health, the occurrence and development of diseases and the rapid recovery of the body. Gastrointestinal cancers are the major diseases affecting human health worldwide. With the development of metagenomic technology and the wide application of new generation sequencing technology, a large number of studies suggest that complex GMs are related to the occurrence and development of gastrointestinal cancers. Fecal microbiota transplantation (FMT) and probiotics can treat and prevent the occurrence of gastrointestinal cancers. This article reviews the latest research progress of microbes in gastrointestinal cancers from the perspectives of the correlation, the influence mechanism and the application, so as to provide new directions for the prevention, early diagnosis and treatment of gastrointestinal cancers.

RevDate: 2021-04-08

Kazemian N, Kao D, S Pakpour (2021)

Fecal Microbiota Transplantation during and Post-COVID-19 Pandemic.

International journal of molecular sciences, 22(6):.

COVID-19 is a major pandemic facing the world today, which has implications on current microbiome-based treatments such as fecal microbiota transplantation (FMT) used for recurrent Clostridioides difficile infections. The bidirectional relationship between the inhabitants of our gut, the gut microbiota, and COVID-19 pathogenesis, as well as the underlying mechanism involved, must be elucidated in order to increase FMT safety and efficacy. In this perspective, we discuss the crucial cross-talk between the gut microbiota and the lungs, known as the gut-lung axis, during COVID-19 infection, as well as the putative effect of these microorganisms and their functional activity (i.e., short chain fatty acids and bile acids) on FMT treatment. In addition, we highlight the urgent need to investigate the possible impact of COVID-19 on FMT safety and efficacy, as well as instilling stringent screening protocols of donors and recipients during COVID-19 and post-COVID-19 pandemic to produce a cohesive and optimized FMT treatment plan across all centers and in all countries across the globe.

RevDate: 2021-04-13

Basson AR, Cominelli F, A Rodriguez-Palacios (2021)

'Statistical Irreproducibility' Does Not Improve with Larger Sample Size: How to Quantify and Address Disease Data Multimodality in Human and Animal Research.

Journal of personalized medicine, 11(3):.

Poor study reproducibility is a concern in translational research. As a solution, it is recommended to increase sample size (N), i.e., add more subjects to experiments. The goal of this study was to examine/visualize data multimodality (data with >1 data peak/mode) as cause of study irreproducibility. To emulate the repetition of studies and random sampling of study subjects, we first used various simulation methods of random number generation based on preclinical published disease outcome data from human gut microbiota-transplantation rodent studies (e.g., intestinal inflammation and univariate/continuous). We first used unimodal distributions (one-mode, Gaussian, and binomial) to generate random numbers. We showed that increasing N does not reproducibly identify statistical differences when group comparisons are repeatedly simulated. We then used multimodal distributions (>1-modes and Markov chain Monte Carlo methods of random sampling) to simulate similar multimodal datasets A and B (t-test-p = 0.95; N = 100,000), and confirmed that increasing N does not improve the 'reproducibility of statistical results or direction of the effects'. Data visualization with violin plots of categorical random data simulations with five-integer categories/five-groups illustrated how multimodality leads to irreproducibility. Re-analysis of data from a human clinical trial that used maltodextrin as dietary placebo illustrated multimodal responses between human groups, and after placebo consumption. In conclusion, increasing N does not necessarily ensure reproducible statistical findings across repeated simulations due to randomness and multimodality. Herein, we clarify how to quantify, visualize and address disease data multimodality in research. Data visualization could facilitate study designs focused on disease subtypes/modes to help understand person-person differences and personalized medicine.

RevDate: 2021-04-05

Pham VT, Calatayud M, Rotsaert C, et al (2021)

Antioxidant Vitamins and Prebiotic FOS and XOS Differentially Shift Microbiota Composition and Function and Improve Intestinal Epithelial Barrier In Vitro.

Nutrients, 13(4): pii:nu13041125.

Human gut microbiota (HGM) play a significant role in health and disease. Dietary components, including fiber, fat, proteins and micronutrients, can modulate HGM. Much research has been performed on conventional prebiotics such as fructooligosaccharides (FOS) and galactooligosaccharides (GOS), however, novel prebiotics or micronutrients still require further validation. We assessed the effect of FOS, xylooligosaccharides (XOS) and a mixture of an antioxidant vitamin blend (AOB) on gut microbiota composition and activity, and intestinal barrier in vitro. We used batch fermentations and tested the short-term effect of different products on microbial activity in six donors. Next, fecal inocula from two donors were used to inoculate the simulator of the human microbial ecosystem (SHIME) and after long-term exposure of FOS, XOS and AOB, microbial activity (short- and branched-chain fatty acids and lactate) and HGM composition were evaluated. Finally, in vitro assessment of intestinal barrier was performed in a Transwell setup of differentiated Caco-2 and HT29-MTX-E12 cells exposed to fermentation supernatants. Despite some donor-dependent differences, all three tested products showed beneficial modulatory effects on microbial activity represented by an increase in lactate and SCFA levels (acetate, butyrate and to a lesser extent also propionate), while decreasing proteolytic markers. Bifidogenic effect of XOS was consistent, while AOB supplementation appears to exert a specific impact on reducing F. nucleatum and increasing butyrate-producing B. wexlerae. Functional and compositional microbial changes were translated to an in vitro host response by increases of the intestinal barrier integrity by all the products and a decrease of the redox potential by AOB supplementation.

RevDate: 2021-04-05

Schmidt EKA, Raposo PJF, Madsen KL, et al (2021)

What Makes a Successful Donor? Fecal Transplant from Anxious-Like Rats Does Not Prevent Spinal Cord Injury-Induced Dysbiosis.

Biology, 10(4): pii:biology10040254.

Spinal cord injury (SCI) causes gut dysbiosis and an increased prevalence of depression and anxiety. Previous research showed a link between these two consequences of SCI by using a fecal transplant from healthy rats which prevented both SCI-induced microbiota changes and the subsequent development of anxiety-like behaviour. However, whether the physical and mental state of the donor are important factors in the efficacy of FMT therapy after SCI remains unknown. In the present study, rats received a fecal transplant following SCI from uninjured donors with increased baseline levels of anxiety-like behaviour and reduced proportion of Lactobacillus in their stool. This fecal transplant increased intestinal permeability, induced anxiety-like behaviour, and resulted in minor but long-term alterations in the inflammatory state of the recipients compared to vehicle controls. There was no significant effect of the fecal transplant on motor recovery in rehabilitative training, suggesting that anxiety-like behaviour did not affect the motivation to participate in rehabilitative therapy. The results of this study emphasize the importance of considering both the microbiota composition and the mental state of the donor for fecal transplants following spinal cord injury.

RevDate: 2021-04-08

Mocanu V, Rajaruban S, Dang J, et al (2021)

Repeated Fecal Microbial Transplantations and Antibiotic Pre-Treatment Are Linked to Improved Clinical Response and Remission in Inflammatory Bowel Disease: A Systematic Review and Pooled Proportion Meta-Analysis.

Journal of clinical medicine, 10(5):.

The response of patients with inflammatory bowel disease (IBD) to fecal microbial transplantation (FMT) has been inconsistent possibly due to variable engraftment of donor microbiota. This failure to engraft has resulted in the use of several different strategies to attempt optimization of the recipient microbiota following FMT. The purpose of our study was to evaluate the effects of two distinct microbial strategies-antibiotic pre-treatment and repeated FMT dosing-on IBD outcomes. A systematic literature review was designed and implemented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A medical librarian conducted comprehensive searches in MEDLINE, Embase, Scopus, Web of Science Core Collection, and Cochrane Library on 25 November 2019 and updated on 29 January 2021. Primary outcomes of interest included comparing relapse and remission rates in patients with IBD for a single FMT dose, repeated FMT dosages, and antibiotic pre-treatment groups. Twenty-eight articles (six randomized trials, 20 cohort trials, two case series) containing 976 patients were identified. Meta-analysis revealed that both repeated FMT and antibiotic pre-treatment strategies demonstrated improvements in pooled response and remission rates. These clinical improvements were associated with increases in fecal microbiota richness and α-diversity, as well as the enrichment of several short-chain fatty acid (SCFA)-producing anaerobes including Bifidobacterium, Roseburia, Lachnospiraceae, Prevotella, Ruminococcus, and Clostridium related species.

RevDate: 2021-04-13

Lorente-Picón M, A Laguna (2021)

New Avenues for Parkinson's Disease Therapeutics: Disease-Modifying Strategies Based on the Gut Microbiota.

Biomolecules, 11(3):.

Parkinson's disease (PD) is a multifactorial neurodegenerative disorder that currently affects 1% of the population over the age of 60 years, and for which no disease-modifying treatments exist. Neurodegeneration and neuropathology in different brain areas are manifested as both motor and non-motor symptoms in patients. Recent interest in the gut-brain axis has led to increasing research into the gut microbiota changes in PD patients and their impact on disease pathophysiology. As evidence is piling up on the effects of gut microbiota in disease development and progression, another front of action has opened up in relation to the potential usage of microbiota-based therapeutic strategies in treating gastrointestinal alterations and possibly also motor symptoms in PD. This review provides status on the different strategies that are in the front line (i.e., antibiotics; probiotics; prebiotics; synbiotics; dietary interventions; fecal microbiota transplantation, live biotherapeutic products), and discusses the opportunities and challenges the field of microbiome research in PD is facing.

RevDate: 2021-04-13

Ooijevaar RE, van Nood E, Goorhuis A, et al (2021)

Ten-Year Follow-Up of Patients Treated with Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection from a Randomized Controlled Trial and Review of the Literature.

Microorganisms, 9(3):.

Fecal microbiota transplantation (FMT) has become a well-established treatment for recurrent Clostridioides difficile infection (rCDI). While short-term outcomes and adverse events relating to FMT have been well documented, there still is a paucity of data with regard to long-term safety. In this report, we describe the long-term follow-up of the prospective cohort of the first randomized controlled trial of FMT for rCDI, and review the existing literature. A total of 34 patients were treated with FMT for rCDI. Seven patients were still alive after a follow-up of more than 10 years and three patients were lost to follow-up. None of the 34 patients had experienced a new-onset autoimmune, gastrointestinal, or malignant disorder during follow-up. We did not find any deterioration or amelioration of pre-existing medical conditions. Furthermore, no deaths directly attributable to FMT could be identified. These findings are in accordance with the data in available literature. In conclusion, no long-term adverse events or complications directly attributable to FMT were found in our prospective cohort. Review of the available literature does not point to long-term risks associated with FMT in this elderly population, provided that carefully screened fecal suspensions are being used. No firm conclusion on the long-term safety of FMT in younger patients could be drawn.

RevDate: 2021-04-02

Leung J, S Pham (2021)

A Systematic Review of Fecal Microbiota Transplantation Versus Vancomycin for Treatment of Recurrent Clostridioides difficile Infection.

Gastroenterology nursing : the official journal of the Society of Gastroenterology Nurses and Associates, 44(2):106-115.

Clostridioides difficile infection is a major clinical challenge, which may be associated with severe complications. Clostridioides difficile infection may result in repeated episodes of diarrhea, abdominal pain, and dehydration, leading to an increased risk of mortality. Increasingly high rates of recurrent Clostridioides difficile-associated diarrhea, refractory to antibiotic therapy, are difficult to treat. The suboptimal response to antibiotic therapy has led to the need for fecal microbiota transplantation in addition to the more commonly prescribed antibiotic, vancomycin. This systematic review aims to evaluate the effectiveness of fecal microbiota transplantation in the resolution of recurrent Clostridioides difficile infection in adults, compared with an oral vancomycin regimen alone. A systematic literature search was performed, resulting in three randomized control studies. Results from the studies are conflicting, with different variations of study outcomes. In two of the three randomized control trials, fecal microbiota transplantation was statistically significant in effectively resolving Clostridioides difficile infection, but not significant in the third. Although fecal microbiota transplantation results are promising, there are many different variables within the studies, and further research is recommended to explore the effects of these variables within larger sample sizes.

RevDate: 2021-04-02

Manrique P, Zhu Y, van der Oost J, et al (2021)

Gut bacteriophage dynamics during fecal microbial transplantation in subjects with metabolic syndrome.

Gut microbes, 13(1):1-15.

Metabolic Syndrome (MetS) is a growing public health concern worldwide. Individuals with MetS have an increased risk for cardiovascular (CV) disease and type 2 diabetes (T2D). These diseases - in part preventable with the treatment of MetS - increase the chances of premature death and pose a great economic burden to health systems. A healthy gut microbiota is associated with a reduction in MetS, T2D, and CV disease. Treatment of MetS with fecal microbiota transplantation (FMT) can be effective, however, its success rate is intermediate and difficult to predict. Because bacteriophages significantly affect the microbiota membership and function, the aim of this pilot study was to explore the dynamics of the gut bacteriophage community after FMT in MetS subjects. We performed a longitudinal study of stool bacteriophages from healthy donors and MetS subjects before and after FMT treatment. Subjects were assigned to either a control group (self-stool transplant, n = 3) or a treatment group (healthy-donor-stool transplant; n-recipients = 6, n-donors = 5). Stool samples were collected over an 18-week period and bacteriophage-like particles were purified and sequenced. We found that FMT from healthy donors significantly alters the gut bacteriophage community. Subjects with better clinical outcome clustered closer to the heathy donor group, suggesting that throughout the treatment, their bacteriophage community was more similar to healthy donors. Finally, we identified bacteriophage groups that could explain these differences and we examined their prevalence in individuals from a larger cohort of MetS FMT trial.Trial information-; NTR 2705.

RevDate: 2021-04-01

Qian Q, He W, Tang R, et al (2021)

Implications of gut microbiota in autoimmune liver diseases.

Minerva gastroenterology pii:S2724-5985.21.02860-9 [Epub ahead of print].

Autoimmune liver diseases (AILD) is a group of immune-mediated liver inflammatory diseases with three major forms including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Interaction of both genetic and environmental factors leads to the breakdown of self-tolerance, hence resulting in hyper-responsive of autoantibodies and aggressive autoreactive immune cells. Genetic studies have identified dozens of risk loci associated with initiation and development of AILD. However, the role of exogenous factors remains unclear. Recently, both infectious and inflammatory diseases have been associated with microbiota, which colonizes multiple mucosal surfaces and participates in human physiological process and function in immune system, particularly influencing liver and biliary system via gut-liver axis. Emerging evidence on the role of gut microbiota has expanded our knowledge of AILD in both pathogenesis and potential therapeutic targets, along with putative diagnosis biomarkers. Herein we review the relationship between host and gut microbiota, discuss their potential roles in disease onset and progression, and summarize the compositional and functional alterations of the microbiota in AILD. We also highlight the microbiotabased therapeutics such as antibiotics and fecal microbiota transplantation (FMT).

RevDate: 2021-03-31

Bui TPN, WM de Vos (2021)

Next-generation therapeutic bacteria for treatment of obesity, diabetes, and other endocrine diseases.

Best practice & research. Clinical endocrinology & metabolism pii:S1521-690X(21)00021-X [Epub ahead of print].

The human gut microbiota has appeared as an important factor affecting host health and intestinal bacteria have recently emerged as potential therapeutics to treat diabetes and other endocrine diseases. These mainly anaerobic bacteria have been identified either via comparative "omics" analysis of the intestinal microbiota in healthy and diseased subjects or of data collected by fecal microbiota transplantation studies. Both approaches require advanced and in-depth sequencing technologies to perform massive genomic screening to select bacteria with potential benefits. It has been shown that these potentially therapeutic bacteria can either produce bioactive products that directly influence the host patho-physiology and endocrine systems or produce specific signaling molecules that may do so. These bioactive compounds can be formed via degradation of dietary or host-derived components or the conversion of intermediate compounds produced by fermentation of intestinal bacteria. Several of these bacteria have shown causality in preclinical models and entered clinical phase studies, while their mode of action is being analyzed. In this review, we summarize the research on the most promising bacterial candidates with therapeutic properties with a specific focus on diabetes.

RevDate: 2021-03-30

Li C, Pi G, F Li (2021)

The Role of Intestinal Flora in the Regulation of Bone Homeostasis.

Frontiers in cellular and infection microbiology, 11:579323.

Intestinal flora located within the intestinal tract comprises a large number of cells, which are referred to as the second gene pool of the human body and form a complex symbiotic relationship with the host. The knowledge of the complex interaction between the intestinal flora and various life activities of the host is a novel and rapidly expanding field. Recently, many studies are being conducted on the relationship between the intestinal flora and bone homeostasis and indicate that the intestinal flora can regulate bone homeostasis via the host immune, metabolic, and endocrine systems. What's more, based on several clinical and preclinical pieces of evidence, changing the composition and function of the host intestinal flora through the application of probiotics, prebiotics, and fecal microbiota transplantation is being considered to be a potential novel target for the regulation of bone homeostasis. Here, we searched relevant literature and reviewed the role of the intestinal flora in the regulation of bone homeostasis and its modulating interventions.

RevDate: 2021-03-30

Qi Z, Lyu M, Yang L, et al (2021)

A Novel and Reliable Rat Model of Autism.

Frontiers in psychiatry, 12:549810.

Background: Autism spectrum disorders (ASD) is a complex neurodevelopmental disorder that lacks an ideal animal model to recapitulate the disease state of ASD. Previous studies have reported that transplanting gut microbiota of ASD patients into pregnant mice is sufficient to promote the changes of autism-like behavior in offspring. This study aims to explore whether fecal microbiota transplantation (FMT) can be used as a new method to establish the ASD animal model. Methods: We transplanted the fecal sample extract of ASD children into pregnant rats (rFMT) repeatedly to establish an ASD rat model (oFMT) and compare it with the classical valproic acid (VPA) model (oVPA). Results: First, we reveal that oFMT shows hypoevolutism and typical behavioral characteristics of ASD, consistent with the previous study. Second, the gut microbiota of oFMT mainly consists of Firmicutes and Bacteroidetes, recapitulating the abnormal gut microbiota of ASD. In oFMT, the abundance of Lactobacillus and Collinsella increased (Lactobacillus: oFMT 60.16%, oVPA 64.13%, oCON 40.11%; Collinsella: oFMT 3.73%, oVPA 1.39%, oCON 1.28%), compared with oVPA, gut microbiota also showed high consistency. Third, the expression of 5-hydroxytryptamine (5-HT) in oFMT serum increased, γ-aminobutyric acid (GABA) and norepinephrine (NE) in oFMT serum decreased. Fourth, the gut microbiota of oFMT also has some ASD characteristic gut microbiota not found in oVPA. Fifth, pregnant rat with VPA showed significant immune activation, while those with FMT showed relatively minor immune activation. Limitations: Although the mechanism of establishing FMT autism rat model (oFMT) has not clearly defined, the data show that the model has high structural validity, and FMT model is likely to be a new and reliable potential animal model of ASD, and will have potential value in studying gut microbiota of ASD. Conclusions: The FMT autism rat model has high structural validity, and the FMT model is likely to be a new and reliable potential animal model of ASD.

RevDate: 2021-04-05

Farhadfar N, Gharaibeh RZ, Dahl WJ, et al (2021)

Gut Microbiota Dysbiosis Associated with Persistent Fatigue in Hematopoietic Cell Transplantation Survivors.

Transplantation and cellular therapy pii:S2666-6367(21)00704-1 [Epub ahead of print].

Fatigue is one of the most prevalent and distressing complications among hematopoietic stem cell transplantation (HCT) survivors, negatively affecting physical, social, and emotional domains of quality of life. Chronic systemic inflammation has been linked to alterations in nervous system activity and initiation of distressing symptoms, such as fatigue. Damage to gut mucosa due to alteration in gut microbiota (GM) composition and microbial translocation has been shown to increase systemic proinflammatory cytokines. The aim of this study was to evaluate the relationship between fatigue and GM by measuring the differences in GM composition in HCT survivors with and without persistent fatigue. This cross-sectional study included 30 adults who underwent HCT for a hematologic disease and were at least 1 year post-HCT. Patients with chronic graft-versus-host disease were excluded. Fatigue severity was assessed by the Brief Fatigue Inventory (BFI). Based on the BFI score, patients were grouped into 2 categories: 0 to 3 (without fatigue) and ≥4 (with fatigue). The V1 to V3 region of the 16S rRNA gene from fecal specimens was sequenced using the Illumina MiSeq. Sequencing reads were processed, denoised, and replicated, chimeras were filtered, amplicon sequence variants (ASVs) were generated, and taxonomy was assigned using DADA2. Beta diversity analysis through principal coordinate analysis was generated using the Bray-Curtis dissimilarity matrix, and the difference was tested using linear model with generalized least squares in R. An alpha diversity analysis was performed using Chao1. Linear discriminant analysis effect size (LEfSe) was used to find markers that differ between the 2 groups. Based on the BFI results, patients were categorized into 2 cohorts: with fatigue (n = 14) and without fatigue (n = 16). The 2 cohorts were similar in terms of demographics, disease, and transplant characteristics. Based on the GM analysis, there was a significant difference in GM composition (beta diversity) between the 2 cohorts (P = .001). Alpha diversity (richness) was also significantly lower in survivors with fatigue (P =.002). LEfSe analysis identified 46 discriminative features (P < .05; linear discriminant analysis score >2) whose relative abundance varied significantly among individuals with fatigue and those without fatigue. Ten ASVs were associated with the patients with fatigue, and 36 ASVs were associated with those without fatigue. Several ASVs enriched in survivors with fatigue included organisms such as Klebsiella and Enterococcus, which have been implicated in inflammatory bowel diseases. The ASVs enriched in the cohort without fatigue were members of the Ruminococcaceae family (Oscillospira spp) and the Lachnospiraceae family (Fusicatenibacter and Coprococcus spp), which are known to have the ability to ferment complex plant carbohydrates. These findings show an association between GM composition and fatigue and suggest a microbial contribution to clinically significant fatigue post-HCT, which may guide the development of new approaches to treating fatigue based on manipulation of the GM.

RevDate: 2021-04-02
CmpDate: 2021-04-02

Zaman A, Qazi T, Pai P, et al (2021)

Carriage rates of multidrug-resistant organisms among prospective stool donors.

The Lancet. Infectious diseases, 21(4):454-455.

RevDate: 2021-04-04

Munshi S (2021)

A depressed gut makes for a depressed brain via vagal transmission.

Brain, behavior, and immunity pii:S0889-1591(21)00119-7 [Epub ahead of print].

RevDate: 2021-04-08

Moon CM, SN Hong (2021)

Fecal Microbiota Transplantation beyond Clostridioides Difficile Infection.

Clinical endoscopy, 54(2):149-151.

With advancing analytical methods for gut microbes, many studies have been conducted, revealing that gut microbes cause various diseases, including gastrointestinal and non-gastrointestinal diseases. Accordingly, studies have been actively conducted to analyze the effects on the prevention and treatment of these diseases through changes in intestinal microbes and control of dysbiosis. Fecal microbiota transplantation (FMT) is an effort and is currently being applied to Clostridioides difficile treatment in Korea. Many studies have demonstrated the application of FMT in inflammatory bowel disease, irritable bowel syndrome, non-alcoholic fatty liver disease, metabolic syndrome, obesity, and diabetes. With further studies and accumulation of evidence, FMT could help treat presently untreatable diseases in clinical practice.

RevDate: 2021-04-08

Gweon TG, SY Na (2021)

Next Generation Fecal Microbiota Transplantation.

Clinical endoscopy, 54(2):152-156.

Fecal microbiota transplantation (FMT) is considered as an effective treatment for Clostridioides difficile infection. However, the precise mechanism of FMT is yet to be determined. Human stool consists of the gut microbiota, bacterial debris, and metabolic products. Of these, the intestinal microbiota is the most important factor that exerts therapeutic efficacy in FMT. Fresh donor stool, blended with normal saline, has been employed for traditional FMT. Nevertheless, stool processing is a major impediment in FMT. Frozen stool and capsule formulations have similar efficacy to that of fresh stool. In addition, several novel stool products have been identified. A stool bank that provides stool products with pre-screened donor stool has been established to help physicians and thereby facilitate FMT. Recent next-generation sequencing techniques have been key in facilitating the detailed analysis of the microbiota and gut environment of individual donors and recipients.

RevDate: 2021-03-24

Cheng F, Huang Z, Wei W, et al (2021)

Fecal microbiota transplantation for Crohn's disease: a systematic review and meta-analysis.

Techniques in coloproctology [Epub ahead of print].

BACKGROUND: Crohn's disease (CD) is a chronic idiopathic inflammatory intestinal disorder associated with fecal dysbiosis. Fecal microbiota transplantation (FMT) is an emerging treatment approach for CD. But its efficacy and safety remain controversial. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of FMT in CD patients.

METHODS: Electronic databases were searched for studies that reported efficacy and/or safety of FMT for CD. Clinical remission was established as the primary outcome. Secondary outcome was clinical response. Odds ratios with 95% confidence intervals (CIs) were reported.

RESULTS: In all, 12 trials were included in our study. Pooled analysis showed that 0.62 (95% CI 0.48, 0.81) of CD patients achieved clinical remission and 0.79 (95% CI 0.71, 0.89) of CD patients achieved clinical response post-FMT. Sub-analyses suggested the rate of clinical remission with fresh stool FMT was higher than with frozen stool FMT (73% vs 43%; p < 0.05). Most adverse events were minor and self-resolving and no major FMT-related adverse event has been reported so far.

CONCLUSIONS: The evidence showed that FMT is an effective and safe therapy for CD. FMT may be successful because it increases the overall diversity of enteric microbiome. Additional randomized controlled studies are needed.

RevDate: 2021-03-24

Wang W, Zhai D, Bai Y, et al (2021)

Loss of QKI in macrophage aggravates inflammatory bowel disease through amplified ROS signaling and microbiota disproportion.

Cell death discovery, 7(1):58.

Inflammatory bowel disease (IBD) is a refractory chronic inflammatory illness of the gastrointestinal (GI) tract. Macrophage exerts an important role in IBD development. QKI, as an RNA binding protein, was related with inflammatory responses in bacterial infections by regulating the polarization of macrophages. Therefore, we suspected that QKI-regulated macrophages have the potential to play a certain role in IBD and the underlying mechanism. Our results demonstrated that the mice with macrophage-specific deletion of QKI induced with dextran sodium sulfate (DSS) are more susceptible to IBD development, exhibited a severe leaky gut barrier phenotype and higher intense oxidative stress, which are rescued by treating with butylated hydroxyanisole (BHA), an agonist of NRF2. Mechanically, we observed that Keap1 mRNA in the nucleus was exported to the cytoplasm after LPS stimuli in parallel with QKI reductions, and the removal of QKI by shRNA facilitated Keap1 mRNA nuclear exporting and expression in cytoplasm, consequently NRF2 activation in nucleus was weakened, and led to the impaired antioxidant abilities. In addition, mice models of fecal microbiota transplant (FMT) and the co-culturing of mice epithelia cells with feces derived from the DSS-treated QKI-deficit mice revealed consistently aggravated colitis along with a severe oxidative stress; 16S sequencing analysis substantiated the altered compositions of commensal bacteria too. Overall, the current study represents the first effort to explore the anti-oxidant role of QKI in the intestinal macrophage via post-transcriptional regulation of Keap1 mRNA localization and the relevant NRF2 antioxidant signaling, and the disproportional changes in the microbiota were attributable to the mediation of pathogenic damage in the IBD development of QKI-deficit mice.

RevDate: 2021-03-27

Santiago M, SW Olesen (2021)

16S rRNA sequencing of samples from universal stool bank donors.

BMC research notes, 14(1):108.

OBJECTIVES: Universal stool banks provide stool to physicians for use in treating recurrent Clostridioides difficile infection via fecal microbiota transplantation. Stool donors providing the material are rigorously screened for diseases and disorders with a potential microbiome etiology, and they are likely healthier than the controls in most microbiome datasets. 16S rRNA sequencing was performed on samples from a selection of stool donors at a large stool bank, OpenBiome, to characterize their gut microbial community and to compare samples across different timepoints and sequencing runs.

DATA DESCRIPTION: 16S rRNA sequencing was performed on 200 samples derived from 170 unique stool donations from 86 unique donors. Samples were sequenced on 11 different sequencing runs. We are making this data available because rigorously screened, likely very healthy stool donors may be useful for characterizing and understanding microbial community differences across different populations and will help shed light into the how the microbiome community promotes health and disease.

RevDate: 2021-03-23

Zhang Y, Zhang S, Li B, et al (2021)

Gut microbiota dysbiosis promotes age-related atrial fibrillation by lipopolysaccharide and glucose-induced activation of NLRP3-inflammasome.

Cardiovascular research pii:6184135 [Epub ahead of print].

AIMS: Aging is the most significant contributor to the increasing prevalence of atrial fibrillation (AF). The gut microbiota dysbiosis is involved in age-related diseases. However, whether the aged-associated dysbiosis contributes to age-related AF is still unknown. Direct demonstration that the aged gut microbiota is sufficient to transmit the enhanced AF susceptibility in a young host via microbiota-intestinal barrier-atria axis has not yet been reported. This study aimed to determine whether gut microbiota dysbiosis affects age-related AF.

METHODS AND RESULTS: Herein, by using a fecal microbiota transplantation (FMT) rat model, we demonstrated that the high AF susceptibility of aged rats could be transmitted to a young host. Specially, we found the dramatically increased levels of circulating lipopolysaccharide (LPS) and glucose led to the up-regulated expression of NLR family pyrin domain containing 3 (NLRP3)-inflammasome, promoting the development of AF which depended on the enhanced atrial fibrosis in recipient host. Inhibition of inflammasome by a potent and selective inhibitor of the NLRP3 inflammasome, MCC950, resulted in a lower atrial fibrosis and AF susceptibility. Then we conducted cross-sectional clinical studies to explore the effect of aging on the altering trends with glucose levels and circulating LPS among clinical individuals in two China hospitals. We found that both of serum LPS and glucose levels were progressively increased in elderly patients as compared with those young. Furthermore, the aging phenotype of circulating LPS and glucose levels, intestinal structure and atrial NLRP3-inflammasome of rats were also confirmed in clinical AF patients. Finally, aged rats colonized with youthful microbiota restored intestinal structure and atrial NLRP3-inflammasome activity, which suppressed the development of aged-related AF.

CONCLUSIONS: Collectively, these studies described a novel causal role of aberrant gut microbiota in the pathogenesis of age-related AF, which indicates that the microbiota-intestinal barrier-atrial NLRP3 inflammasome axis may be a rational molecular target for the treatment of aged-related arrhythmia disease.

TRANSLATIONAL PERSPECTIVE: The current study demonstrates that aged-associated microbiota dysbiosis promotes AF in part through a microbiota-gut-atria axis. Increased AF susceptibility due to enhanced atrial NLRP3-inflammasome activity by LPS and high glucose was found in an aged FMT rat model, and also confirmed within elderly clinical individuals. In a long-term FMT rat study, the AF susceptibility was ameliorated by treatment with youthful microbiota. The present findings can further increase our understanding of aged-related AF and address a promising therapeutic strategy that involves modulation of gut microbiota composition.

RevDate: 2021-04-01

Zhang SL, Mao YQ, Zhang ZY, et al (2021)

Pectin supplement significantly enhanced the anti-PD-1 efficacy in tumor-bearing mice humanized with gut microbiota from patients with colorectal cancer.

Theranostics, 11(9):4155-4170.

Background: Anti-PD-1-based immunotherapy has emerged as a promising therapy for several cancers. However, it only benefits a small subset of colorectal cancer (CRC) patients. Mounting data supports the pivotal role of gut microbiota in shaping immune system. Pectin, a widely consumed soluble fiber, has been reported to ameliorate the imbalance of gut microbiota. Therefore, we aimed to explore the effect and the underlying mechanisms of pectin in improving anti-PD-1 mAb efficacy. Methods: The C57BL/6 mice were treated with a broad-spectrum antibiotic (ATB) cocktail to depleted endogenous gut microbiota and subsequently humanized with feces from healthy controls or newly diagnosed CRC patients. The antitumor efficacies of anti-PD-1 mAb combined with or without pectin were assessed using these mice. Flow cytometry and immunohistochemistry (IHC) were conducted to investigate the tumor immune microenvironment after treatment. The gut microbiota profiles and short-chain fatty acids (SCFAs) levels were determined by 16S ribosomal RNA (16S rRNA) gene sequencing and gas chromatography-mass spectrometry (GC-MS), respectively. The effect of gut microbiota on anti-PD-1 mAb efficacy after pectin supplement was further tested by fecal microbiota transplantation (FMT). Results: The anti-PD-1 mAb efficacy was largely impaired in the mice humanized with feces from newly diagnosed CRC patients compared to those from healthy controls. However, pectin significantly enhanced the anti-PD-1 mAb efficacy in the tumor-bearing mice humanized with CRC patient gut microbiota. Flow cytometry and IHC analysis revealed increased T cell infiltration and activation in the tumor microenvironment of mice treated with anti-PD-1 mAb plus pectin. In vivo depletion of CD8+ T cells diminished the anti-tumor effect of anti-PD-1 mAb combined with pectin. 16S rRNA gene sequencing showed that pectin significantly increased gut microbial diversity and beneficially regulated microbial composition. In addition, we identified unique bacterial modules that were significantly enriched in the anti-PD-1 mAb + pectin group, which composed of butyrate-producing bacteria indicative of good response to immunotherapy. Meanwhile, GC-MS showed that pectin altered the level of SCFA butyrate. Furthermore, butyrate, a main product of dietary fiber in gut microbial fermentation, was found to be sufficient to promote T cells infiltration and thus enhance the efficacy of anti-PD-1 mAb. In addition, FMT demonstrated the effects of pectin were dependent on gut microbiota. Importantly, the beneficial effects of pectin were confirmed in the mice humanized with gut microbiota from patient with resistance to anti-PD-1 mAb. Conclusion: Pectin facilitated the anti-PD-1 mAb efficacy in CRC via regulating the T cell infiltration in the tumor microenvironment, which was potentially mediated by the metabolite butyrate.

RevDate: 2021-04-01

Lu J, Chen PP, Zhang JX, et al (2021)

GPR43 deficiency protects against podocyte insulin resistance in diabetic nephropathy through the restoration of AMPKα activity.

Theranostics, 11(10):4728-4742.

Rationale: Albuminuria is an early clinical feature in the progression of diabetic nephropathy (DN). Podocyte insulin resistance is a main cause of podocyte injury, playing crucial roles by contributing to albuminuria in early DN. G protein-coupled receptor 43 (GPR43) is a metabolite sensor modulating the cell signalling pathways to maintain metabolic homeostasis. However, the roles of GPR43 in podocyte insulin resistance and its potential mechanisms in the development of DN are unclear. Methods: The experiments were conducted by using kidney tissues from biopsied DN patients, streptozotocin (STZ) induced diabetic mice with or without global GPR43 gene knockout, diabetic rats treated with broad-spectrum oral antibiotics or fecal microbiota transplantation, and cell culture model of podocytes. Renal pathological injuries were evaluated by periodic acid-schiff staining and transmission electron microscopy. The expression of GPR43 with other podocyte insulin resistance related molecules was checked by immunofluorescent staining, real-time PCR, and Western blotting. Serum acetate level was examined by gas chromatographic analysis. The distribution of gut microbiota was measured by 16S ribosomal DNA sequencing with faeces. Results: Our results demonstrated that GPR43 expression was increased in kidney samples of DN patients, diabetic animal models, and high glucose-stimulated podocytes. Interestingly, deletion of GPR43 alleviated albuminuria and renal injury in diabetic mice. Pharmacological inhibition and knockdown of GPR43 expression in podocytes increased insulin-induced Akt phosphorylation through the restoration of adenosine 5'-monophosphate-activated protein kinase α (AMPKα) activity. This effect was associated with the suppression of AMPKα activity through post-transcriptional phosphorylation via the protein kinase C-phospholipase C (PKC-PLC) pathway. Antibiotic treatment-mediated gut microbiota depletion, and faecal microbiota transplantation from the healthy donor controls substantially improved podocyte insulin sensitivity and attenuated glomerular injury in diabetic rats accompanied by the downregulation of the GPR43 expression and a decrease in the level of serum acetate. Conclusion: These findings suggested that dysbiosis of gut microbiota-modulated GPR43 activation contributed to albuminuria in DN, which could be mediated by podocyte insulin resistance through the inhibition of AMPKα activity.

RevDate: 2021-03-31

Beyaz Coşkun A, AG Sağdiçoğlu Celep (2021)

Therapeutic modulation methods of gut microbiota and gut-liver axis.

Critical reviews in food science and nutrition [Epub ahead of print].

Liver diseases are considered global health problems that cause more than 1 million deaths each year. Due to the increase in the prevalence of liver diseases worldwide, studies on different treatment methods have increased. Some of these methods is diagnostic and therapeutic applications based on the examination of the intestinal and intestinal microbiota. In this study, research articles, systematic review and review in the literature were examined in order to determine gut-liver axis relationship and treatment methods for liver diseases with gut modulation methods. Studies related to the subject have been searched in Google Scholar and Pubmed databases. The keywords "liver disease" and "gut-liver axis" and "microbiota" and "gut modulation methods" or "probiotic" or "prebiotic" or "symbiotic" or "antibiotic" or "bile acid regulation" or "adsorbent" or "fecal microbiota transplantation" were used in the searches. Improvements have been achieved in biomarkers of liver diseases by providing intestinal modulation with probiotic, prebiotic, symbiotic, antibiotic and adsorbents applications, bile acid regulation and fecal microbiota transplantation. In the results of experimental and clinical studies, it was seen that the therapeutic potential of the treatments performed by applying probiotics, prebiotics and symbiotics was higher.

RevDate: 2021-03-22

Tixier EN, Verheyen E, Luo Y, et al (2021)

Systematic Review with Meta-Analysis: Fecal Microbiota Transplantation for Severe or Fulminant Clostridioides difficile.

Digestive diseases and sciences [Epub ahead of print].

BACKGROUND: Severe and fulminant Clostridioides difficile infection (CDI) is associated with significant morbidity and mortality. While fecal microbiota transplantation (FMT) has proved to be a highly effective treatment for recurrent CDI, its efficacy in severe or fulminant CDI remains uncertain.

AIMS: To perform a systematic review with meta-analysis evaluating clinical outcomes and safety of FMT in severe and fulminant CDI.

METHODS: A systemic review with meta-analysis was performed through comprehensive search of Embase, Medline (Ovid), trial registers, and conference abstracts through January 2020. Studies on FMT in severe and fulminant CDI were included. Meta-analysis was done with random effects models given heterogeneity to estimate rates of cure, mortality, and colectomy. Publication bias was assessed using Egger's test.

RESULTS: Sixteen studies comprised of one randomized controlled trial, four cohort studies, and eleven case series were analyzed. In total, 676 patients underwent FMT for severe or fulminant CDI. The overall rate of clinical cure after single FMT was 61.3% (95% CI 43.2-78.0%) with 10.9% (95% CI 0.2-30.2%) of patients experiencing major adverse events. The overall pooled colectomy rate after FMT was 8.2% (95% CI 0.1-23.7%) with a pooled all-cause mortality rate after FMT of 15.6% (95% CI 7.8-25.0%).

CONCLUSION: Low-quality data support the use of fecal microbiota transplantation in patients with severe and fulminant Clostridioides difficile infection.

RevDate: 2021-03-21

Chu Q, Zhang S, Yu X, et al (2021)

Fecal microbiota transplantation attenuates nano-plastics induced toxicity in Caenorhabditis elegans.

The Science of the total environment, 779:146454 pii:S0048-9697(21)01522-9 [Epub ahead of print].

Current studies simply focus on the toxicity of nano-plastics, while the correlation between their toxicity and bio-distribution, as well as intestinal microorganisms is still blank. Therefore, we systematically evaluated the toxicity based on the accumulation characteristics of nano-plastics in C. elegans. Meanwhile, for the first time, human fecal microbiota was transplanted into the gut of C. elegans and found that nano-plastics can through the intestinal barrier to the whole body after oral intake and can't be drastically excreted until die, thus causing toxic effects; while human fecal microbiota transplantation can significantly improve the living state via activating PMK-1/SKN-1 pathway to promote the production of intracellular glutathione, and exogenous glutathione addition can also markedly protect nematodes against nano-plastics induced toxicity. Our results not only provide a fully understand between the accumulation characteristic and health risk of nano-plastics, but also take C. elegans and intestinal flora into the field of toxicity evolution of nanomaterials.

RevDate: 2021-03-20

Rao J, Xie R, Lin L, et al (2021)

Fecal microbiota transplantation ameliorates gut microbiota imbalance and intestinal barrier damage in rats with stress-induced depressive-like behavior.

The European journal of neuroscience [Epub ahead of print].

The gut-microbiota-brain axis is the most important complex and bidirectional pathway between the gastrointestinal tract and the central nervous system. This study investigated the potential of microbe-induced gut-to-brain signaling to modulate the effect of stress on depressive-like behavior, intestinal barrier, and neuroinflammation. Result showed that fecal microbiota transplantation increased the consumption of sucrose solutions and decreased the immobility time in forced swimming test. This treatment also increased Firmicutes and decreased Bacteroidetes and Desulfobacterota at phylum levels; reduced the loss of villi and epithelial cells; suppressed the inflammatory cell infiltration in ileum; increased the expression of ZO-1, occludin; protected the mucosal layer function; and suppressed the high levels of inflammasomes (NLRP3, ASC, caspase-1, and IL-1β) in rat brain. In summary, fecal microbiota transplantation improves the depressive-like behavior, alters the gut microbiota imbalance, and alleviates intestinal tract inflammation, intestinal mucosa disruption, and neuroinflammation in rats induced by chronic unpredictable mild stress.

RevDate: 2021-04-13

Agranyoni O, Meninger-Mordechay S, Uzan A, et al (2021)

Gut microbiota determines the social behavior of mice and induces metabolic and inflammatory changes in their adipose tissue.

NPJ biofilms and microbiomes, 7(1):28.

The link between the gut microbiota and social behavior has been demonstrated, however the translational impact of a certain microbiota composition on stable behavioral patterns is yet to be elucidated. Here we employed an established social behavior mouse model of dominance (Dom) or submissiveness (Sub). A comprehensive 16S rRNA gene sequence analysis of Dom and Sub mice revealed a significantly different gut microbiota composition that clearly distinguishes between the two behavioral modes. Sub mice gut microbiota is significantly less diverse than that of Dom mice, and their taxa composition uniquely comprised the genera Mycoplasma and Anaeroplasma of the Tenericutes phylum, in addition to the Rikenellaceae and Clostridiaceae families. Conversely, the gut microbiota of Dom mice includes the genus Prevotella of the Bacteriodetes phylum, significantly less abundant in Sub mice. In addition, Sub mice show lower body weight from the age of 2 weeks and throughout their life span, accompanied with lower epididymis white adipose tissue (eWAT) mass and smaller adipocytes together with substantially elevated expression of inflammation and metabolic-related eWAT adipokines. Finally, fecal microbiota transplantation into germ-free mice show that Sub-transplanted mice acquired Sub microbiota and adopted their behavioral and physiological features, including depressive-like and anti-social behaviors alongside reduced eWAT mass, smaller adipocytes, and a Sub-like eWAT adipokine profile. Our findings demonstrate the critical role of the gut microbiome in determining dominance vs. submissiveness and suggest an association between gut microbiota, the eWAT metabolic and inflammatory profile, and the social behavior mode.

RevDate: 2021-03-19

Xi W, Gao X, Zhao H, et al (2021)

Depicting the composition of gut microbiota in children with tic disorders: an exploratory study.

Journal of child psychology and psychiatry, and allied disciplines [Epub ahead of print].

BACKGROUND: Symptom improvement in children with tic disorder (TD) following fecal microbiota transplantation led us to investigate the gut microbiota in TD. This exploratory study aims to depict the gut microbial profile in patients with TD and explore the impact of dopamine receptor antagonist (DRA) drugs on the composition and metabolic function of the gut microbiota.

METHODS: The gut microbiota were profiled in fecal samples of 49 children with TD and 50 matched healthy controls (HC) using shotgun metagenomic sequencing. A random forest (RF) model was constructed using the gut bacterial species to distinguish TD from HC. Associations between clinical metadata and microbial abundance or function were analyzed using MaAsLin2 and Spearman correlation.

RESULTS: The gut microbiota in children with TD was featured by higher abundances of Bacteroides plebeius and Ruminococcus lactaris (a potential pro-inflammatory taxon) and lower abundances of Prevotella stercorea and Streptococcus lutetiensis compared to HC. The constructed RF model accurately distinguished TD from HC based on the gut microbiota profile, resulting in an AUC of 0.884. Significant correlations were observed between tic symptom severity and the abundances of multiple bacterial species and gut microbiota metabolic functions. Multivariate analysis identified an upregulation of 4-aminobutanoate (GABA) degradation in the gut microbiota associated with TD status. The gut microbiota of DRA-treated TD children showed a distinct gut microbiota compared to the treatment-naïve group, represented by an increase in some potential enteric pathogens such as Escherichia coli, a decline in several species including Akkermansia muciniphila, and alterations in various metabolic functions.

CONCLUSIONS: Bacterial species promoting inflammatory responses and those modulating neurotransmitters such as GABA may be involved in the pathogenesis of TD. The use of DRA drugs is likely to induce overgrowth of some enteric pathogens and alter the gut microbiota metabolism.

RevDate: 2021-03-19

Li H, Zhuang P, Zhang Y, et al (2021)

Mixed conjugated linoleic acid sex-dependently reverses high-fat diet-induced insulin resistance via the gut-adipose axis.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 35(4):e21466.

Conjugated linoleic acid (CLA) may prevent the development of obesity and metabolic disorders. However, the effects of CLA on inflammation and glucose metabolism are controversial. The underlying mechanisms governing the gut microbiota and sexual dimorphisms have also not been elucidated. The present study assessed the effect of CLA on glucose and lipid metabolism in established obesity and examined the mechanism of action based on gut microbiota. Four-week-old C57BL/6J mice were fed a high-fat diet (HFD) for 10 weeks to induce obesity. The diet-induced obese (DIO) mice were fed an HFD supplemented with mixed CLA (50% cis-9, trans-11 isomer and 50% trans-10, cis-12 isomers, 0.2% wt/wt) for 15 weeks. CLA supplementation remarkably reversed body weight in both sexes. CLA favored anti-inflammatory microbiota in male mice, mediating increased short-chain fatty acids and decreased lipopolysaccharide (LPS) production, which alleviated global inflammation and improved insulin sensitivity via inhibition of the TLR4-NF-κB pathway in adipose tissue. CLA promoted the growth of hydrogen sulfide-producing Desulfovibrio and the release of LPS in female mice, which aggravated adipose inflammation and insulin resistance. Although CLA impaired glucose metabolism in females, brown adipose tissue was significantly activated with browning of white adipose tissue in both sexes, which led to enhanced energy expenditure. Fecal transplantation from CLA-treated mice to DIO mice mimicked the sex-dependent phenotype. In conclusion, CLA decreased body weight and increased energy expenditure but sex-dependently modulated insulin resistance via the gut-adipose axis.

RevDate: 2021-03-17

Jin G, Tang Q, Ma J, et al (2021)

Maternal Emulsifier P80 Intake Induces Gut Dysbiosis in Offspring and Increases Their Susceptibility to Colitis in Adulthood.

mSystems, 6(2):.

Early life events can lead to multiple diseases in adulthood. Previous studies suggested that polysorbate 80 (P80) as a widely used emulsifier in pharmaceutical formulations and food industries could impair the intestinal barrier. However, whether maternal P80 (MP80) exposure could affect the long-term health of offspring remains unknown. In this study, we found that maternal P80 intake could retard intestinal development, disrupt the intestinal barrier, and cause low-grade intestinal inflammation in 3-week-old offspring. 16S rRNA sequencing and correlation analysis revealed that Mucispirillum, Clostridium XI, and Parabacteroides, which positively correlated with intestinal proliferation and differentiation, were decreased in the maternal P80 group. Interestingly, the increase in some harmful bacteria, including Proteobacteria, Helicobacteraceae, Campylobacterales, and Desulfovibrionales, persisted from the weaning period to adulthood (3 to 8 weeks). Furthermore, a fecal microbiota transplantation assay showed that the mice gavaged with feces from 3-week-old offspring of the MP80 group presented more severe intestinal inflammation and barrier disruption than the mice that received feces from the offspring of the control group. Finally, maternal P80 intake remarkably aggravated the structural disorder of intestinal crypt, increased proinflammatory factors, and exacerbated dextran sulfate sodium (DSS)-induced colitis in adulthood. Conclusively, maternal P80 intake could induce gut dysbiosis and promote colitis susceptibility in adulthood. This study provides new insights into the prevention of inflammatory bowel disease (IBD).IMPORTANCE The main findings of this research showed that maternal P80 intake could disrupt the intestinal barrier, induce gut dysbiosis, and promote colitis susceptibility in adulthood. This study will enhance understanding of the prevention of IBD.

RevDate: 2021-03-16

Gilca-Blanariu GE, Stefanescu G, Girleanu I, et al (2021)

Romanian National Guideline on Translating Fecal Microbiota Transplantation Applications related to Clostridioides difficile Infections into the Local Clinical Practice.

Journal of gastrointestinal and liver diseases : JGLD, 30(1):147-163.

Fecal microbiota transplantation involves the infusion of intestinal microorganisms via the transfer of a stool from a healthy individual into a diseased individual, with the intent of restoring normal intestinal flora. Fecal transplant is proposed for the treatment of refractory Clostridioides difficile infection. At present, recurrent Clostridioides difficile infection is the only indication supported by solid scientific evidence. Regulations by healthcare authorities vary among different countries. Considering that Romania does not have an available national guideline to offer standardization, this paper aimed to create a national fecal microbiota transplantation guideline concerning indications, techniques and donor screening, developed by international and local scientific working groups.

RevDate: 2021-03-19

Tang X, Wang W, Hong G, et al (2021)

Gut microbiota-mediated lysophosphatidylcholine generation promotes colitis in intestinal epithelium-specific Fut2 deficiency.

Journal of biomedical science, 28(1):20.

BACKGROUND AND AIMS: Previous study disclosed Fucosyltransferase 2 (Fut2) gene as a IBD risk locus. This study aimed to explore the mechanism of Fut2 in IBD susceptibility and to propose a new strategy for the treatment of IBD.

METHODS: Intestinal epithelium-specific Fut2 knockout (Fut2△IEC) mice was used. Colitis was induced by dextran sulfate sodium (DSS). The composition and diversity of gut microbiota were assessed via 16S rRNA analysis and the metabolomic findings was obtained from mice feces via metabolite profiling. The fecal microbiota transplantation (FMT) experiment was performed to confirm the association of gut microbiota and LPC. WT mice were treated with Lysophosphatidylcholine (LPC) to verify its impact on colitis.

RESULTS: The expression of Fut2 and α-1,2-fucosylation in colonic tissues were decreased in patients with UC (UC vs. control, P = 0.036) and CD (CD vs. control, P = 0.031). When treated with DSS, in comparison to WT mice, more severe intestinal inflammation and destructive barrier functions in Fut2△IEC mice was noted. Lower gut microbiota diversity was observed in Fut2△IEC mice compared with WT mice (p < 0.001). When exposed to DSS, gut bacterial diversity and composition altered obviously in Fut2△IEC mice and the fecal concentration of LPC was increased. FMT experiment revealed that mice received the fecal microbiota from Fut2△IEC mice exhibited more severe colitis and higher fecal LPC concentration. Correlation analysis showed that the concentration of LPC was positively correlated with four bacteria-Escherichia, Bilophila, Enterorhabdus and Gordonibacter. Furthermore, LPC was proved to promote the release of pro-inflammatory cytokines and damage epithelial barrier in vitro and in vivo.

CONCLUSION: Fut2 and α-1,2-fucosylation in colon were decreased not only in CD but also in UC patients. Gut microbiota in Fut2△IEC mice is altered structurally and functionally, promoting generation of LPC which was proved to promote inflammation and damage epithelial barrier.

RevDate: 2021-03-16

Delli Bovi AP, Marciano F, Mandato C, et al (2021)

Oxidative Stress in Non-alcoholic Fatty Liver Disease. An Updated Mini Review.

Frontiers in medicine, 8:595371.

Non-alcoholic fatty liver disease (NAFLD) is a challenging disease caused by multiple factors, which may partly explain why it remains still orphan of an adequate therapeutic strategy. Herein we focus on the interplay between oxidative stress (OS) and the other causal pathogenetic factors. Different reactive oxygen species (ROS) generators contribute to NAFLD inflammatory and fibrotic progression, which is quite strictly linked to the lipotoxic liver injury from fatty acids and/or a wide variety of their biologically active metabolites in the context of either a two-hit or a (more recent) multiple parallel hits theory. An antioxidant defense system is usually able to protect hepatic cells from damaging effects caused by ROS, including those produced into the gastrointestinal tract, i.e., by-products generated by usual cellular metabolic processes, normal or dysbiotic microbiota, and/or diet through an enhanced gut-liver axis. Oxidative stress originating from the imbalance between ROS generation and antioxidant defenses is under the influence of individual genetic and epigenetic factors as well. Healthy diet and physical activity have been shown to be effective on NAFLD also with antioxidant mechanisms, but compliance to these lifestyles is very low. Among several considered antioxidants, vitamin E has been particularly studied; however, data are still contradictory. Some studies with natural polyphenols proposed for NAFLD prevention and treatment are encouraging. Probiotics, prebiotics, diet, or fecal microbiota transplantation represent new therapeutic approaches targeting the gut microbiota dysbiosis. In the near future, precision medicine taking into consideration genetic or environmental epigenetic risk factors will likely assist in further selecting the treatment that could work best for a specific patient.

RevDate: 2021-03-16

Żebrowska P, Łaczmańska I, Ł Łaczmański (2021)

Future Directions in Reducing Gastrointestinal Disorders in Children With ASD Using Fecal Microbiota Transplantation.

Frontiers in cellular and infection microbiology, 11:630052.

Research on the use of fecal microbiota transplantation (FMT) in the treatment of disorders related to digestive system ailments in children with autism spectrum disorders (ASDs) is a new attempt in a therapeutic approach. There are very little scientific evidences available on this emerging alternative method. However, it appears to be interesting not only because of its primary outcome, relieving the gastrointestinal (GI) symptoms, but also secondary therapeutic effect of alleviating autistic behavioral symptoms. FMT seems to be also promising method in the treatment of another group of pediatric patients, children with inflammatory bowel disease (IBD). The aim of this study is to discuss the potential use of FMT and modified protocols (MTT, microbiota transfer therapy) in the treatment of GI disorders in ASD children supported by reports on another disease, IBD concerning pediatric patients. Due to the few reports of the use of FMT in the treatment of children, these two patients groups were selected, although suffering from distant health conditions: neurodevelopmental disorder and gastrointestinal tract diseases, because of the the fact that they seem related in aspects of the presence of GI symptoms, disturbed intestinal microbiota, unexplained etiology of the condition and age range of patients. Although the outcomes for all are promising, this type of therapy is still an under-researched topic, studies in the group of pediatric patients are sparse, also there is a high risk of transmission of infectious and noninfectious elements during the procedure and no long-term effects on global health are known. For those reasons all obtained results should be taken with a great caution. However, in the context of future therapeutic directions for GI observed in neurodevelopmental disorders and neurodegenerative diseases, the topic seems worthy of attention.

RevDate: 2021-04-07

Cortés P, Bi Y, Stancampiano F, et al (2021)

Clostridioides Difficile Infection: A comprehensive review for primary providers.

Romanian journal of internal medicine = Revue roumaine de medecine interne pii:rjim-2021-0010 [Epub ahead of print].

Clostridioides Difficile infection (CDI) is an issue of great concern due to its rising incidence, recurrence, morbidity and impact on healthcare spending. Treatment guidelines have changed in the last few years, and new therapies are being considered. This is a practical review for the primary care practitioner of the latest guidelines for CDI diagnosis, treatment and emerging therapies.

RevDate: 2021-04-11

Qian XH, Song XX, Liu XL, et al (2021)

Inflammatory pathways in Alzheimer's disease mediated by gut microbiota.

Ageing research reviews, 68:101317 pii:S1568-1637(21)00064-7 [Epub ahead of print].

In the past decade, numerous studies have demonstrated the close relationship between gut microbiota and the occurrence and development of Alzheimer's disease (AD). However, the specific mechanism is still unclear. Both the neuroinflammation and systemic inflammation serve as the key hubs to accelerate the process of AD by promoting pathology and damaging neuron. What's more, the gut microbiota is also crucial for the regulation of inflammation. Therefore, this review focused on the role of gut microbiota in AD through inflammatory pathways. Firstly, this review summarized the relationship and interaction among gut microbiota, inflammation, and AD. Secondly, the direct and indirect regulatory effects of gut microbiota on AD through inflammatory pathways were described. These effects were mainly mediated by the component of the gut microbiota (lipopolysaccharides (LPS) and amyloid peptides), the metabolites of bacteria (short-chain fatty acids, branched amino acids, and neurotransmitters) and functional by-products (bile acids). In addition, potential treatments (fecal microbiota transplantation, antibiotics, probiotics, prebiotics, and dietary interventions) for AD were also discussed through these mechanisms. Finally, according to the current research status, the key problems to be solved in the future studies were proposed.

RevDate: 2021-04-06

Long D, Liu M, Li H, et al (2021)

Dysbacteriosis induces abnormal neurogenesis via LPS in a pathway requiring NF-κB/IL-6.

Pharmacological research, 167:105543 pii:S1043-6618(21)00127-4 [Epub ahead of print].

In this study, we identified elevated levels of LPS and suppressed neurogenesis in a successfully established mouse model of gut microbiota dysbiosis. We mimicked these phenotypes using mouse and chicken embryos exposed to LPS and found that dramatic variation in gene expression was due to changes in the dorsal-ventral patterning of the neural tube. Cell survival and excess ROS were also involved in this process. Antioxidant administration alleviated LPS-activated NF-κB signaling, while directly blocking NF-κB signaling altered the LPS-induced inhibition of neurogenesis. Furthermore, IL-6 was proven to play a vital role in the expression of crucial neurogenesis-related genes and NF-κB. In summary, we found that the suppression of neurogenesis induced by dysbacteriosis-derived LPS was significantly reversed in mice with fecal microbiota transplantation. This study reveals that gut dysbacteriosis-derived LPS impairs embryonic neurogenesis, and that the NF-κB/IL-6 pathway could be one of the main factors triggering the downstream signaling cascade.

RevDate: 2021-03-13

Song A, Shen N, Gan C, et al (2021)

Exploration of the relationship between intestinal flora changes and gut acute graft-versus-host disease after hematopoietic stem cell transplantation.

Translational pediatrics, 10(2):283-295.

Background: Acute graft-versus-host disease (aGVHD) is a life-threatening factor for post-hematopoietic stem cell transplantation (HSCT) patients. To investigate the relationship between intestinal flora changes and gut aGVHD after HSCT, we performed this cross-sectional study.

Methods: We selected children from our medical center from July 2016 to January 2017. Fifty-six samples from 42 patients and 6 samples from normal children met the study criteria and were analyzed. Fecal 16S RNA sequencing was completed before transplantation or on days 7, 28 or 100 post-transplantation. The intestinal infection and GVHD clinical data were retrospectively analyzed, and the survival risk factors were analyzed. Correlation analysis was performed with the feces bioinformatic data.

Results: The GVHD group alpha diversity was the lowest, which was significantly different than that of the non-diarrhea group (P value=0.032). A richer posttransplantation relative abundance of Moraxellaceae was conducive to survival, while that of Enterococcaceae and Alphaproteobacteria was not. Similarly, a rich relative abundance of Proteobacteria, Gammaproteobacteria and Odoribacteraceae in the intestinal flora before HSCT contributed to patient death thereafter. Regarding diarrhea, the GVHD group exhibited a richer Pasteurellales and Pasteurellaceae relative abundances, which showed strong correlations with diarrhea severity. Peptostreptococcaceae, Bifidobacteriales and Bifidobacteriaceae were richer in relative abundance in the intestinal infection group and correlated with pretransplant characteristics.

Conclusions: The gut microbiota diversity was lowest when gut aGVHD occurred, which was consistent with the clinically higher mortality rate and greater treatment difficulty. Pasteurellaceae played an important role in gut aGVHD and diarrhea severity. Bifidobacteriaceae led to infectious diarrhea after HSCT. Specific bacteria were biomarkers for survival: Moraxellaceae, Enterococcaceae and Alphaproteobacteria from the intestinal flora after HSCT and Proteobacteria, Gammaproteobacteria and Odoribacteraceae before HSCT.

RevDate: 2021-03-13

Su Y, Li X, Li D, et al (2021)

Fecal Microbiota Transplantation Shows Marked Shifts in the Multi-Omic Profiles of Porcine Post-weaning Diarrhea.

Frontiers in microbiology, 12:619460.

Weaning is the most critical phase in pig production and is generally associated with significant impacts on intestinal morphology, structure, physiology, and immune responses, which can lead to subsequent production inefficiencies such as decreases in growth and intake and increases in morbidity and mortality. In the present study, we attempted to explore the effects of fecal microbiota transplantation (FMT) on the fecal microbiota, fecal metabolites, and transcriptome in the jejunum, colon, liver, spleen, and oral mucosa in piglets with post-weaning diarrhea and to evaluate the therapeutic potential of FMT in piglets with post-weaning diarrhea. We found that FMT partially relieved the symptoms of diarrhea in piglets, and microbiota analysis results indicated that unclassified_f_Prevotellaceae was identified as an FMT-associated bacterial family at 66 day and that the Shannon index in the healthy group at 34, 38, and 66 days were higher than that at 21 day. Functional enrichment analysis of the oral mucosa, liver, jejunum, and colon showed that most of the differentially expressed genes (DEGs) were enriched in the terms metabolic process, immune response, and inflammatory response. Moreover, the enriched fecal metabolites focused mostly on apoptosis, beta-alanine metabolism, glutathione metabolism, and sphingolipid metabolism. We tried to detect specific "metabolite-bacterium" pairs, such as "g_Catenisphaera-stigmastentriol," "p_Bacteroidetes-(6beta,22E)-6-hydroxystigmasta-4,22-dien-3-one," and "g_Prevotellaceae_NK3B31_group-stenocereol." Overall, the present study provides a theoretical basis for the alleviation of weaning stress and contributes to the realization of effective and sustainable application of FMT in the pig production industry in the future.

RevDate: 2021-03-23

Wang G, Hu YX, He MY, et al (2021)

Gut-Lung Dysbiosis Accompanied by Diabetes Mellitus Leads to Pulmonary Fibrotic Change through the NF-κB Signaling Pathway.

The American journal of pathology pii:S0002-9440(21)00087-0 [Epub ahead of print].

Growing evidence shows that the lungs are an unavoidable target organ of diabetic complications. However, the pathologic mechanisms of diabetic lung injury are still controversial. This study demonstrated the dysbiosis of the gut and lung microbiome, pulmonary alveolar wall thickening, and fibrotic change in streptozotocin-induced diabetic mice and antibiotic-induced gut dysbiosis mice compared with controls. In both animal models, the NF-κB signaling pathway was activated in the lungs. Enhanced pulmonary alveolar well thickening and fibrotic change appeared in the lungs of transgenic mice expressing a constitutively active NF-κB mutant compared with wild type. When lincomycin hydrochloride-induced gut dysbiosis was ameliorated by fecal microbiota transplant, enhanced inflammatory response in the intestine and pulmonary fibrotic change in the lungs were significantly decreased compared with lincomycin hydrochloride-treated mice. Furthermore, the application of fecal microbiota transplant and baicalin could also redress the microbial dysbiosis of the gut and lungs in streptozotocin-induced diabetic mice. Taken together, the study data suggest that multiple as yet undefined factors related to microbial dysbiosis of gut and lungs cause pulmonary fibrogenesis associated with diabetes mellitus through an NF-κB signaling pathway.

RevDate: 2021-04-06

Koretz RL (2021)

JPEN Journal Club 61. Testing hypotheses.

JPEN. Journal of parenteral and enteral nutrition [Epub ahead of print].

RevDate: 2021-04-06

Gu M, Samuelson DR, Taylor CM, et al (2021)

Alcohol-associated intestinal dysbiosis alters mucosal-associated invariant T-cell phenotype and function.

Alcoholism, clinical and experimental research [Epub ahead of print].

BACKGROUND: Chronic alcohol consumption is associated with a compromised innate and adaptive immune responses to infectious disease. Mucosa-associated invariant T (MAIT) cells play a critical role in antibacterial host defense. However, whether alcohol-associated deficits in innate and adaptive immune responses are mediated by alterations in MAIT cells remains unclear.

METHODS: To investigate the impact of alcohol on MAIT cells, mice were treated with binge-on-chronic alcohol for 10 days and sacrificed at day 11. MAIT cells in the barrier organs (lung, liver, and intestine) were characterized by flow cytometry. Two additional sets of animals were used to examine the involvement of gut microbiota on alcohol-induced MAIT cell changes: (1) Cecal microbiota from alcohol-fed (AF) mice were adoptive transferred into antibiotic-pretreated mice and (2) AF mice were treated with antibiotics during the experiment. MAIT cells in the barrier organs were measured via flow cytometry.

RESULTS: Binge-on-chronic alcohol feeding led to a significant reduction in the abundance of MAIT cells in the barrier tissues. However, CD69 expression on tissue-associated MAIT cells was increased in AF mice compared with pair-fed (PF) mice. The expression of Th1 cytokines and the corresponding transcriptional factor was tissue specific, showing downregulation in the intestine and increases in the lung and liver in AF animals. Transplantation of fecal microbiota from AF mice resulted in a MAIT cell profile aligned to that of AF mouse donor. Antibiotic treatment abolished the MAIT cell differences between AF and PF animals.

CONCLUSION: MAIT cells in the intestine, liver, and lung are perturbed by alcohol use and these changes are partially attributable to alcohol-associated dysbiosis. MAIT cell dysfunction may contribute to alcohol-induced innate and adaptive immunity and consequently end-organ pathophysiology.

RevDate: 2021-03-12

Kaiser T, Nalluri H, Zhu Z, et al (2021)

Donor Microbiota Composition and Housing Affect Recapitulation of Obese Phenotypes in a Human Microbiota-Associated Murine Model.

Frontiers in cellular and infection microbiology, 11:614218.

Human microbiota-associated (HMA) mouse models offer a valuable approach to study the role of intestinal microbiota in the development of obesity. In this study, we used an HMA model to evaluate whether engraftment of human obese or lean microbiota, from each of three donors, could recapitulate host phenotypes under conventional and specific-pathogen-free housing. Microbiota engraftment was correlated with donor relative abundances of the class Bacteroidia (Spearman's ρ = 0.73, P ≤ 0.001), and one obese donor resulted in significant weight gain (P ≤ 0.003) and compromised insulin sensitivity under conventional housing. SPF housing partially blunted phenotypic response. Results of this study indicate that our HMA model partially recapitulates obese phenotypes under conventional housing and highlights a need to consider donor-specific effects as well as housing conditions when studying the role of the microbiota in obesity.

RevDate: 2021-03-12

Liu J, Xu Y, B Jiang (2021)

Novel Insights Into Pathogenesis and Therapeutic Strategies of Hepatic Encephalopathy, From the Gut Microbiota Perspective.

Frontiers in cellular and infection microbiology, 11:586427.

Since the 1950s, gradual changes in the gut microbiota of patients with hepatic encephalopathy have been observed. Previous research has indicated potential associations between the gut and brain, and the gut microbiota is becoming a hot topic in research on diseases of the nervous system. However, for the past few decades, studies of hepatic encephalopathy have been restricted to controlling the gut microbiota during macroscopic manipulation, such as probiotic intervention, while its clinical use remains controversial, and the cellular mechanisms underlying this condition are still poorly understood. This thesis seeks to comprehensively understand and explain the role of gut microbiota in hepatic encephalopathy as well as analyze the effects of intervention by regulating the gut microbiota. Evidence is presented that shows that dysbiosis of the gut microbiota is the primary pathological driver of hepatic encephalopathy and impacts pathologic progression via complex regulatory networks. As a result, suggestions were identified for future mechanistic research and improvements in therapeutic strategies for hepatic encephalopathy.

RevDate: 2021-03-17

Gupta S, Zhu J, McCarty TR, et al (2021)

Cost-effectiveness analysis of sequential fecal microbiota transplantation for fulminant Clostridioides difficile infection.

Journal of gastroenterology and hepatology [Epub ahead of print].

BACKGROUND AND AIM: Fulminant Clostridioides difficile infections (FCDI) account for 8% of cases and substantial healthcare burden. Fecal microbiota transplantation is recommended for recurrent CDI, but emerging data support use for FCDI. We aimed to assess the cost-effectiveness of a sequential fecal microbiota transplantation (sFMT) protocol for FCDI compared with current standard therapy.

METHODS: A Markov model simulated patients with FCDI in a 1-year time horizon. The treatment algorithm for up to three sFMTs, clinical probabilities, and direct costs were used from published sources. Outcomes were quality-adjusted life years (QALYs) and costs. The healthcare sector perspective was used with a willingness-to-pay threshold of $100 000 per QALY.

RESULTS: Sequential fecal microbiota transplantation (FMT) for FCDI was associated with lower overall cost ($28 309 vs $33 980) and higher QALY (0.765 vs 0.686) compared with standard therapy. sFMT is cost-effective in 100% of iterations. sFMT remained cost-effective at cure rates > 44.8% for the first FMT and at stool preparation cost < $6944 per instillation. We find a wide range of efficacies for the first versus second FMT at which sFMT is still preferred. Value of information analysis estimates the expected value of perfect information to be low at $1.89 per person, quantified with net monetary benefit.

CONCLUSIONS: An sFMT strategy strongly dominates standard therapy, with lower cost and higher QALY. Sensitivity analysis demonstrates benefit even if FMT cure rates are lower than expected and when multiple FMTs are required. FMT material in 2020 was priced at $1695 per treatment but remains cost-effective at a much higher cost.

RevDate: 2021-03-16
CmpDate: 2021-03-16

Jing Y, Yu Y, Bai F, et al (2021)

Effect of fecal microbiota transplantation on neurological restoration in a spinal cord injury mouse model: involvement of brain-gut axis.

Microbiome, 9(1):59.

BACKGROUND: Spinal cord injury (SCI) patients display disruption of gut microbiome, and gut dysbiosis exacerbate neurological impairment in SCI models. Cumulative data support an important role of gut microbiome in SCI. Here, we investigated the hypothesis that fecal microbiota transplantation (FMT) from healthy uninjured mice into SCI mice may exert a neuroprotective effect.

RESULTS: FMT facilitated functional recovery, promoted neuronal axonal regeneration, improved animal weight gain and metabolic profiling, and enhanced intestinal barrier integrity and GI motility in SCI mice. High-throughput sequencing revealed that levels of phylum Firmicutes, family Christensenellaceae, and genus Butyricimonas were reduced in fecal samples of SCI mice, and FMT remarkably reshaped gut microbiome. Also, FMT-treated SCI mice showed increased amount of fecal short-chain fatty acids (SCFAs), which correlated with alteration of intestinal permeability and locomotor recovery. Furthermore, FMT downregulated IL-1β/NF-κB signaling in spinal cord and NF-κB signaling in gut following SCI.

CONCLUSION: Our study demonstrates that reprogramming of gut microbiota by FMT improves locomotor and GI functions in SCI mice, possibly through the anti-inflammatory functions of SCFAs. Video Abstract.

RevDate: 2021-04-09

Rao J, Qiao Y, Xie R, et al (2021)

Fecal microbiota transplantation ameliorates stress-induced depression-like behaviors associated with the inhibition of glial and NLRP3 inflammasome in rat brain.

Journal of psychiatric research, 137:147-157 pii:S0022-3956(21)00135-7 [Epub ahead of print].

BACKGROUND: Evidence from previous studies has demonstrated that the gut-microbiota-brain axis is vital in regulating of behavior and neuroinflammation in the central nervous system. Considering the putative connection among gut microbiota, neural function, and behavior, the present study investigated the potential signaling of gut microbiota to modulate depression-like behaviors and neuroinflammation.

METHODS: Rats showing depression-like behaviors induced by chronic unpredictable mild stress received fecal microbiota treatment or vehicle for 14 days, and alterations in behavior and neuroinflammation were assessed. ELISA, immunofluorescence staining and Western blot were used to analysis the activation of glial cells and NLRP3 inflammasome.

RESULTS: Treatment with fecal microbiota transplantation ameliorated depression-like behaviors. 5-Hydroxytryptamine decreased in the chronic unpredictable mild stress rat model but significantly increased after fecal microbiota transplantation. The treatment with fecal microbiota transplantation decreased the production of IL-1β and TNF-α. Moreover, fecal microbiota transplantation administration suppressed the activation of Iba1 positive microglia cells and GFAP positive astrocytes cells and reduced the expression of NLRP3, ASC, Caspase-1, and IL-1β pathway in the prefrontal cortex and hippocampus.

CONCLUSIONS: Fecal microbiota transplantation can improve depression-like behaviors induced by chronic unpredictable mild stress. The anti-depression effects of fecal microbiota transplantation were associated with the suppressed activation of glial cells and NLRP3 inflammasome in the brain.

RevDate: 2021-03-16

Verdier C, Denis S, Gasc C, et al (2021)

An Oral FMT Capsule as Efficient as an Enema for Microbiota Reconstruction Following Disruption by Antibiotics, as Assessed in an In Vitro Human Gut Model.

Microorganisms, 9(2):.

Fecal microbiota transplantation (FMT) is an innovative therapy already used in humans to treat Clostridioides difficile infections associated with massive use of antibiotics. Clinical studies are obviously the gold standard to evaluate FMT efficiency but remain limited by regulatory, ethics, and cost constraints. In the present study, an in vitro model of the human colon reproducing medically relevant perturbation of the colonic ecosystem by antibiotherapy was used to compare the efficiency of traditional FMT enema formulations and a new oral capsule in restoring gut microbiota composition and activity. Loss of microbial diversity, shift in bacterial populations, and sharp decrease in fermentation activities induced in vivo by antibiotherapy were efficiently reproduced in the in vitro model, while capturing inter-individual variability of gut microbiome. Oral capsule was as efficient as enema to decrease the number of disturbed days and bacterial load had no effect on enema performance. This study shows the relevance of human colon models as an alternative approach to in vivo assays during preclinical studies for evaluating FMT efficiency. The potential of this in vitro approach could be extended to FMT testing in the management of many digestive or extra-intestinal pathologies where gut microbial dysbiosis has been evidenced such as inflammatory bowel diseases, obesity or cancers.

RevDate: 2021-03-16

Shabbir U, Arshad MS, Sameen A, et al (2021)

Crosstalk between Gut and Brain in Alzheimer's Disease: The Role of Gut Microbiota Modulation Strategies.

Nutrients, 13(2):.

The gut microbiota (GM) represents a diverse and dynamic population of microorganisms and about 100 trillion symbiotic microbial cells that dwell in the gastrointestinal tract. Studies suggest that the GM can influence the health of the host, and several factors can modify the GM composition, such as diet, drug intake, lifestyle, and geographical locations. Gut dysbiosis can affect brain immune homeostasis through the microbiota-gut-brain axis and can play a key role in the pathogenesis of neurodegenerative diseases, including dementia and Alzheimer's disease (AD). The relationship between gut dysbiosis and AD is still elusive, but emerging evidence suggests that it can enhance the secretion of lipopolysaccharides and amyloids that may disturb intestinal permeability and the blood-brain barrier. In addition, it can promote the hallmarks of AD, such as oxidative stress, neuroinflammation, amyloid-beta formation, insulin resistance, and ultimately the causation of neural death. Poor dietary habits and aging, along with inflammatory responses due to dysbiosis, may contribute to the pathogenesis of AD. Thus, GM modulation through diet, probiotics, or fecal microbiota transplantation could represent potential therapeutics in AD. In this review, we discuss the role of GM dysbiosis in AD and potential therapeutic strategies to modulate GM in AD.

RevDate: 2021-03-10

Giampaolino P, Foreste V, Di Filippo C, et al (2021)

Microbiome and PCOS: State-of-Art and Future Aspects.

International journal of molecular sciences, 22(4):.

Polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine disease. The hypothesis that alterations in the microbiome are involved in the genesis of PCOS has been postulated. Aim of this review is to summarize the available literature data about the relationship between microbiome and PCOS. A search on PubMed and Medline databases was performed from inception to November 20Most of evidence has focused on the connection of intestinal bacteria with sex hormones and insulin-resistance: while in the first case, a relationship with hyperandrogenism has been described, although it is still unclear, in the second one, chronic low-grade inflammation by activating the immune system, with increased production of proinflammatory cytokines which interfere with insulin receptor function, causing IR (Insulin Resistance)/hyperinsulinemia has been described, as well as the role of gastrointestinal hormones like Ghrelin and peptide YY (PYY), bile acids, interleukin-22 and Bacteroides vulgatus have been highlighted. The lower genital tract microbiome would be affected by changes in PCOS patients too. The therapeutic opportunities include probiotic, prebiotics and synbiotics, as well as fecal microbiota transplantation and the use of IL-22, to date only in animal models, as a possible future drug. Current evidence has shown the involvement of the gut microbiome in PCOS, seen how humanized mice receiving a fecal transplant from women with PCOS develop ovarian dysfunction, immune changes and insulin resistance and how it is capable of disrupting the secondary bile acid biosynthesis. A future therapeutic approach for PCOS may involve the human administration of IL-22 and bile acid glycodeoxycholic acid.

RevDate: 2021-03-10

Ciernikova S, Mego M, M Chovanec (2021)

Exploring the Potential Role of the Gut Microbiome in Chemotherapy-Induced Neurocognitive Disorders and Cardiovascular Toxicity.

Cancers, 13(4):.

Chemotherapy, targeting not only malignant but also healthy cells, causes many undesirable side effects in cancer patients. Due to this fact, long-term cancer survivors often suffer from late effects, including cognitive impairment and cardiovascular toxicity. Chemotherapy damages the intestinal mucosa and heavily disrupts the gut ecosystem, leading to gastrointestinal toxicity. Animal models and clinical studies have revealed the associations between intestinal dysbiosis and depression, anxiety, pain, impaired cognitive functions, and cardiovascular diseases. Recently, a possible link between chemotherapy-induced gut microbiota disruption and late effects in cancer survivors has been proposed. In this review, we summarize the current understanding of preclinical and clinical findings regarding the emerging role of the microbiome and the microbiota-gut-brain axis in chemotherapy-related late effects affecting the central nervous system (CNS) and heart functions. Importantly, we provide an overview of clinical trials evaluating the relationship between the gut microbiome and cancer survivorship. Moreover, the beneficial effects of probiotics in experimental models and non-cancer patients with neurocognitive disorders and cardiovascular diseases as well as several studies on microbiota modulations via probiotics or fecal microbiota transplantation in cancer patients are discussed.

RevDate: 2021-03-05

Ranallo RT, Clifford McDonald L, Laufer Halpin A, et al (2021)

The State of Microbiome Science at the Intersection of Infectious Diseases and Antimicrobial Resistance.

The Journal of infectious diseases pii:6154668 [Epub ahead of print].

Along with the rise in modern chronic diseases, ranging from diabetes to asthma, lay the challenges posed by increasing antibiotic resistance resulting in difficult to treat infections, as well as sepsis. An emerging and unifying theme in the pathogenesis of these diverse public health threats is changes in the microbial communities that inhabit multiple body sites. Although there is great promise in exploring the role of these microbial communities in chronic disease pathogenesis, the shorter timeframe of most infectious disease pathogenesis may allow early translation of our basic scientific understanding of microbial ecology and host-microbiota-pathogen interactions. Likely translation avenues include development of preventive strategies, diagnostics, and therapeutics. For example, as basic research related to microbial pathogenesis continues to progress, Clostridioides difficile infection (CDI) is already being addressed clinically through at least two of these three avenues: targeted antibiotic stewardship and treatment of recurrent disease through fecal microbiota transplantation (FMT).

RevDate: 2021-03-05

El-Salhy M, Patcharatrakul T, S Gonlachanvit (2021)

The role of diet in the pathophysiology and management of irritable bowel syndrome.

Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology [Epub ahead of print].

Irritable bowel syndrome (IBS) is a chronic gastrointestinal (GI) disorder that reportedly affects 5% to 20% of the world population. The etiology of IBS is not completely understood, but diet appears to play an important role in its pathophysiology. Asian diets differ considerably from those in Western countries, which might explain differences in the prevalence, sex, and clinical presentation seen between patients with IBS in Asian and Western countries. Dietary regimes such as a low-fermentable oligo-, di-, monosaccharides, and polyols (FODMAP) diet and the modified National Institute for Health and Care Excellence (NICE) diet improve both symptoms and the quality of life in a considerable proportion of IBS patients. It has been speculated that diet is a prebiotic for the intestinal microbiota and favors the growth of certain bacteria. These bacteria ferment the dietary components, and the products of fermentation act upon intestinal stem cells to influence their differentiation into enteroendocrine cells. The resulting low density of enteroendocrine cells accompanied by low levels of certain hormones gives rise to intestinal dysmotility, visceral hypersensitivity, and abnormal secretion. This hypothesis is supported by the finding that changing to a low-FODMAP diet restores the density of GI cells to the levels in healthy subjects. These changes in gut endocrine cells caused by low-FODMAP diet are also accompanied by improvements in symptoms and the quality of life.

RevDate: 2021-03-05

Kopper JJ, Alexander TL, Kogan CJ, et al (2021)

In Vitro Evaluation of the Effect of Storage at -20°C and Proximal Gastrointestinal Conditions on Viability of Equine Fecal Microbiota Transplant.

Journal of equine veterinary science, 98:103360.

Fecal microbiota transplant (FMT), a technique used to restore normal intestinal microbial communities, has been successful in treating humans with Clostridioides difficile colitis. Subsequently, FMT is being used in veterinary patients with suspected intestinal dysbiosis. Unfortunately, little data are available regarding best practices for FMT in horses. The objective of this study was to evaluate the effects of storing manure prepared for equine FMT (MP-FMT) at -20°C for up to 4 weeks and passage through a simulated proximal gastrointestinal (GI) tract on the viability of MP-FMT. The results of this study indicate that storage at -20°C for greater than 1 week and exposure to conditions consistent with the proximal GI tract significantly decreased viability of the microbial population, with gram-negative enteric bacteria most significantly impacted. This preliminary evaluation indicates that further work is necessary to determine best practices to preserve the viability MP-FMT in horses.

RevDate: 2021-03-30

Xu JY, Liu MT, Tao T, et al (2021)

The role of gut microbiota in tumorigenesis and treatment.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 138:111444 pii:S0753-3322(21)00229-8 [Epub ahead of print].

A large number of microbial communities exist in normal human intestinal tracts, which maintain a relatively stable dynamic balance under certain conditions. Gut microbiota are closely connected with human health and the occurrence of tumors. The colonization of certain intestinal bacteria on specific sites, gut microbiota disturbance and intestinal immune disorders can induce the occurrence of tumors. Meanwhile, gut microbiota can also play a role in tumor therapy by participating in immune regulation, influencing the efficacy of anti-tumor drugs, targeted therapy of engineered probiotics and fecal microbiota transplantation. This article reviews the role of gut microbiota in the occurrence, development, diagnosis and treatment of tumors. A better understanding of how gut microbiota affect tumors will help us find more therapies to treat the disease.

RevDate: 2021-04-02

Mikolašević I, Hauser G, Abram M, et al (2021)

Fecal microbiota transplantation - where are we?.

Croatian medical journal, 62(1):52-58.

RevDate: 2021-03-05

Khurana S, Kahl A, Yu K, et al (2020)

Recent advances in the treatment of Clostridioides difficile infection: the ever-changing guidelines.

Faculty reviews, 9:13.

Clostridioides difficile infection (CDI), formerly known as Clostridium difficile, continues to be the most common healthcare-associated infection worldwide. With the shifting epidemiology towards higher a incidence of community-acquired CDI and the continued burden on the healthcare system posed by high rates of CDI recurrence, there has been an impetus to advance the diagnostic testing and treatment strategies. Recent advancements over the past decade have led to rapidly changing guidelines issued by the Infectious Diseases Society of America and European Society of Clinical Microbiology and Infectious Diseases. With our comprehensive review, we aim to summarize the latest advances in diagnosing and treating CDI and thus attempt to help readers guide best practices for patient care. This article also focusses on cost-effectiveness of various therapies currently available on the market and provides an analysis of the current evidence on a relatively new monoclonal antibody therapy, Bezlotoxumab, to treat recurrent CDI.

RevDate: 2021-03-04

Тикунов АЮ, Морозов ВВ, Швалов АН, et al (2020)

[Fecal microbiome change in patients with ulcerative colitis after fecal microbiota transplantation].

Vavilovskii zhurnal genetiki i selektsii, 24(2):168-175.

Intestinal human microbiota is a dynamic system that is under the pressures of its host organism and external factors. Microbiota disruption caused by these factors can lead to severe diseases including inflammatory and oncological diseases of the gastrointestinal tract. One of the possible approaches in managing the intestinal microbiota is fecal microbiota transplantation (FT) - transfer of the microbiota from the stool of a healthy donor to the intestinal tract of a recipient patient. Currently, this procedure is recognized as an efficacious method to normalize the intestinal microbiota mainly in inflammatory diseases of the gastrointestinal tract. In Russia, pilot studies of the effectiveness of FT in patients with ulcerative colitis have been conducted for several years, and these studies were started in Novosibirsk. The aim of this study was to assess the change of intestinal microbiome in 20 patients with ulcerative colitis after a single FT procedure. The main method is a comparative analysis of 16S ribosomal RNA sequence libraries constructed using fecal samples obtained from patients with ulcerative colitis before and after FT and sequenced on the Illumina MiSeq platform. The obtained results showed that FT led to an increase in average biodiversity in samples after FT compared to samples before FT; however, the difference was not significant. In the samples studied, the proportion of Firmicutes sequences, the major gastrointestinal microbiota of healthy people, was decreased (~32 % vs. >70 %), while the proportion of Proteobacteria sequences was increased (>9 % vs. <5 %). In some samples collected before FT, sequences of pathogenic Firmicutes and Proteobacteria were detected, including Acinetobacter spp., Enterococcus spp., Klebsiella pneumoniae, Proteus mirabilis, Staphylococcus aureus, Stenotrophomonas maltophylia, Streptococcus spp. In most cases, the proportion of such sequences after FT substantially decreased in appropriate samples. The exception was the Clostridium difficile sequences, which accounted for <0.5 % of the sequences in samples from almost half of the patients and after FT, the share of such C. difficile sequences was significantly reduced only in samples from three patients. It should be noted that the proportion of Lactobacillus spp. increased ten-fold and their species composition significantly expanded. According to the obtained results, a preliminary conclusion can be made that even a single FT procedure can lead to an increase in the biodiversity of the gastrointestinal microbiota in patients and to the optimization of the taxonomic composition of the microbiota.

RevDate: 2021-04-07

Huang J, Shan W, Li F, et al (2021)

Fecal microbiota transplantation mitigates vaginal atrophy in ovariectomized mice.

Aging, 13(5):7589-7607.

Vulvovaginal atrophy (VVA) is a common menopause-related symptom affecting more than 50% of midlife and older women and cancer patients whose ovarian function are lost or damaged. Regardless of estrogen deficiency, whether other factors such as the gut microbiota play role in VVA have not been thoroughly investigated. To this end, we performed ovariectomy on 12-weeks' old mice and follow-up at 4 weeks after ovariectomy, and observed atrophied vagina and an altered gut microbiota in ovariectomized mice.. We further performed fecal microbiota transplantation with feces from another cohort of ovary-intact fecund female mice to the ovariectomized ones, and found that the vaginal epithelial atrophy was significantly alleviated as well as the gut microbiota was pointedly changed. All these results suggest that ovarian activity has some influence on the gut microbiota, and the latter from the ovary-intact female mice can somehow make the vagina of mice deficient in ovarian function healthier maybe by up-expressing ESR1 in vaginal cells and enhancing regeneration in vagina. This kind of association between gut microbiota and vaginal health need further exploration such that it may provide an alternative treatment by modulating gut microbiota in patients suffering from VVA but may be reluctant to hormone therapy.

RevDate: 2021-03-21
CmpDate: 2021-03-11

Liao C, Taylor BP, Ceccarani C, et al (2021)

Compilation of longitudinal microbiota data and hospitalome from hematopoietic cell transplantation patients.

Scientific data, 8(1):71.

The impact of the gut microbiota in human health is affected by several factors including its composition, drug administrations, therapeutic interventions and underlying diseases. Unfortunately, many human microbiota datasets available publicly were collected to study the impact of single variables, and typically consist of outpatients in cross-sectional studies, have small sample numbers and/or lack metadata to account for confounders. These limitations can complicate reusing the data for questions outside their original focus. Here, we provide comprehensive longitudinal patient dataset that overcomes those limitations: a collection of fecal microbiota compositions (>10,000 microbiota samples from >1,000 patients) and a rich description of the "hospitalome" experienced by the hosts, i.e., their drug exposures and other metadata from patients with cancer, hospitalized to receive allogeneic hematopoietic cell transplantation (allo-HCT) at a large cancer center in the United States. We present five examples of how to apply these data to address clinical and scientific questions on host-associated microbial communities.

RevDate: 2021-03-03

Dalal RS, JR Allegretti (2021)

Diagnosis and management of Clostridioides difficile infection in patients with inflammatory bowel disease.

Current opinion in gastroenterology pii:00001574-900000000-99052 [Epub ahead of print].

PURPOSE OF REVIEW: Clostridioides difficile infection (CDI) may complicate the course of ulcerative colitis and Crohn's disease. The clinical presentation of CDI in this population is often atypical, and patients may experience exacerbations of their underlying inflammatory bowel disease (IBD) secondary to C. difficile. In this review, we aim to review the risk factors, diagnosis, and management of CDI in the context of IBD.

RECENT FINDINGS: Patients with colonic involvement of their IBD are at higher risk for CDI and colonization may be more common than in the general population. Therefore, CDI is confirmed using a two-step approach to stool testing. Oral vancomycin or fidaxomicin are the preferred agents for nonfulminant disease, and oral metronidazole is no longer recommended as first-line therapy. For all patients with CDI recurrence, fecal microbiota transplant (FMT) should be considered, as this has been shown to be safe and effective. Among those who have worsening of their underlying IBD, retrospective research suggest that outcomes are improved for those who undergo escalation of immunosuppression with appropriate antimicrobial treatment of C. difficile, however prospective data are needed.

SUMMARY: CDI may complicate the course of IBD, however the presentation may not be typical. Therefore, all patients with worsening gastrointestinal symptoms should be evaluated for both CDI and IBD exacerbation. Providers should consider FMT for all patients with recurrent CDI as well as escalation of immunosuppression for patients who fail to improve with appropriate antimicrobial therapy.

RevDate: 2021-04-07

Grajeda-Iglesias C, Durand S, Daillère R, et al (2021)

Oral administration of Akkermansia muciniphila elevates systemic antiaging and anticancer metabolites.

Aging, 13(5):6375-6405.

The presence of Akkermansia muciniphila (Akk) in the human gut is associated with good health, leanness and fitness. Mouse experimentation has demonstrated positive effects for Akk, which counteracts aging, mediates antiobesity and antidiabetic effects, dampens inflammation and improves anticancer immunosurveillance. Clinical trials have confirmed antidiabetic effects for Akk. Here, we investigated the time-dependent effects of oral administration of Akk (which was live or pasteurized) and other bacteria to mice on the metabolome of the ileum, colon, liver and blood plasma. Metabolomics was performed by a combination of chromatographic and mass spectrometric methods, yielding a total of 1.637.227 measurements. Akk had major effects on metabolism, causing an increase in spermidine and other polyamines in the gut and in the liver. Pasteurized Akk (Akk-past) was more efficient than live Akk in elevating the intestinal concentrations of polyamines, short-chain fatty acids, 2-hydroxybutyrate, as well multiple bile acids, which also increased in the circulation. All these metabolites have previously been associated with human health, providing a biochemical basis for the beneficial effects of Akk.

RevDate: 2021-04-13

Khor B, Snow M, Herrman E, et al (2021)

Interconnections Between the Oral and Gut Microbiomes: Reversal of Microbial Dysbiosis and the Balance Between Systemic Health and Disease.

Microorganisms, 9(3):.

The human microbiota represents a complex array of microbial species that influence the balance between the health and pathology of their surrounding environment. These microorganisms impart important biological benefits to their host, such as immune regulation and resistance to pathogen colonization. Dysbiosis of microbial communities in the gut and mouth precede many oral and systemic diseases such as cancer, autoimmune-related conditions, and inflammatory states, and can involve the breakdown of innate barriers, immune dysregulation, pro-inflammatory signaling, and molecular mimicry. Emerging evidence suggests that periodontitis-associated pathogens can translocate to distant sites to elicit severe local and systemic pathologies, which necessitates research into future therapies. Fecal microbiota transplantation, probiotics, prebiotics, and synbiotics represent current modes of treatment to reverse microbial dysbiosis through the introduction of health-related bacterial species and substrates. Furthermore, the emerging field of precision medicine has been shown to be an effective method in modulating host immune response through targeting molecular biomarkers and inflammatory mediators. Although connections between the human microbiome, immune system, and systemic disease are becoming more apparent, the complex interplay and future innovations in treatment modalities will become elucidated through continued research and cross-disciplinary collaboration.

RevDate: 2021-03-30

Yang S, Hu T, Liu H, et al (2021)

Akebia saponin D ameliorates metabolic syndrome (MetS) via remodeling gut microbiota and attenuating intestinal barrier injury.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 138:111441 pii:S0753-3322(21)00226-2 [Epub ahead of print].

Metabolic syndrome (MetS) is a complex, multifactorial disease which lead to an increased risk of cardiovascular disease, type 2 diabetes, and stroke. However, selective, and potent drugs for the treatment of MetS are still lacking. Previous studies have found that Akebia saponin D (ASD) has beneficial effects on metabolic diseases such as obesity, atherosclerosis, and non-alcoholic fatty liver disease (NAFLD). Therefore, our study was designed to determine the effect and mechanism of action of ASD against MetS in a high-fat diet (HFD) induced mouse model. ASD significantly decreased plasma lipid and insulin resistance in these mice, and a targeted approach using metabolomic analyses of plasma and feces indicated that glucose and lipids in these mice crossed the damaged intestinal barrier into circulation. Furthermore, ASD was able to increase lipid excretion and inhibit intestinal epithelial lipid absorption. Results for gut microbiota composition showed that ASD significantly reduced HFD-associated Alistipes, Prevotella, and enhanced the proportions of Butyricimonas, Ruminococcus, and Bifidobacterium. After 14 weeks of ASD/fecal microbiota transplantation (FMT) interventions the developed gut barrier dysfunction was restored. Additionally, RNA-seq revealed that ASD reduced the lipid-induced tight junction (TJ) damage in intestinal epithelial cells via down-regulation of the PPAR-γ-FABP4 pathway in vitro and that use of the PPAR-γ inhibitor (T0070907) was able to partially block the effects of ASD, indicating that the PPAR-γ/FABP4 pathway is a critical mediator involved in the improvement of MetS. Our results demonstrated that ASD not only modifies the gut microbiome but also ameliorates the HFD-induced gut barrier disruption via down-regulation of the PPAR-γ-FABP4 pathway. These findings suggest a promising, and novel therapeutic strategy for gut protection against MetS.

RevDate: 2021-03-02

Ghorbani Y, Schwenger KJP, JP Allard (2021)

Manipulation of intestinal microbiome as potential treatment for insulin resistance and type 2 diabetes.

European journal of nutrition [Epub ahead of print].

PURPOSE: Increasing evidence suggests that the intestinal microbiome (IM) and bacterial metabolites may influence glucose homeostasis, energy expenditure and the intestinal barrier integrity and lead to the presence of systemic low-grade inflammation, all of which can contribute to insulin resistance (IR) and type 2 diabetes (T2D). The purpose of this review is to explore the role of the IM and bacterial metabolites in the pathogenesis and treatment of these conditions.

RESULTS: This review summarizes research focused on how to modulate the IM through diet, prebiotics, probiotics, synbiotics and fecal microbiota transplant in order to treat IR and T2D.

CONCLUSION: There is an abundance of evidence suggesting a role for IM in the pathogenesis of IR and T2D based on reviewed studies using various methods to modulate IM and metabolites. However, the results are inconsistent. Future research should further assess this relationship.

RevDate: 2021-03-05

Al-Bakri AG, Akour AA, WK Al-Delaimy (2021)

Knowledge, attitudes, ethical and social perspectives towards fecal microbiota transplantation (FMT) among Jordanian healthcare providers.

BMC medical ethics, 22(1):19.

BACKGROUND: Fecal microbiota transplant (FMT) is a treatment modality that involves the introduction of stool from a healthy pre-screened donor into the gastrointestinal tract of a patient. It exerts its therapeutic effects by remodeling the gut microbiota and treating microbial dysbiosis-imbalance. FMT is not regulated in Jordan, and regulatory effort for FMT therapy in Jordan, an Islamic conservative country, might be faced with unique cultural, social, religious, and ethical challenges. We aimed to assess knowledge, attitudes, and perceptions of ethical and social issues of FMT use among Jordanian healthcare professionals.

METHODS: An observational, cross-sectional study design was used to assess knowledge, attitudes, and perceptions of ethical and social issues of FMT among 300 Jordanian healthcare professionals.

RESULTS: A large proportion (39 %) thought that the safety and efficacy of this technique are limited and 29.3 % thought there is no evidence to support its use. Almost all (95 %) responded that they would only perform it in certain cases, if ethically justified, and 48.3 % would use it due to treatment failure of other approaches. When reporting about reasons for not using it, 40 % reported that they would not perform it due to concerns about medical litigation, fear of infections (38 %), and lack of knowledge of long safety and efficacy (31.3 %). Interestingly, all practitioners said they would perform this procedure through the lower rather than upper gastrointestinal tract modality and the majority will protect the patient's confidentiality via double-blinding (43.3 %). For a subset of participants (n = 100), the cultural constraints that might affect the choice of performing FMT were mainly due to donor's religion, followed by dietary intake, and alcohol consumption.

CONCLUSIONS: Our healthcare practitioners are generally reluctant to use the FMT modality due to religious and ethical reasons but would consider it if there was a failure of other treatment and after taking into consideration many legislative, social, ethical and practice-based challenges including safety, efficacy and absence of guidelines.

RevDate: 2021-03-02
CmpDate: 2021-03-02

Afecto E, Ponte A, Fernandes S, et al (2021)

Fecal microbiota transplantation in hepatic encephalopathy : a review of the current evidence and future perspectives.

Acta gastro-enterologica Belgica, 84(1):87-90.

Hepatic encephalopathy (HE) is a leading cause of hospitalization and morbimortality in advanced cirrhosis with limited therapeutic options available. Given the paramount role of gut microbiota in HE, and the efficacy of fecal microbiota transplantation (FMT) in other diseases, this review intends to summarize the evidence supporting the safety, efficacy and future perspectives of FMT in HE. Current evidence, despite being scarce, points towards FMT being a safe, effective and tolerable procedure in HE. Some unanswered questions remain about the optimal dose, the administration route, the long term effects and the selection of the optimal donor. Future trials, some of which are already underway, will provide us additional evidence and hopefully the necessary answers.

RevDate: 2021-02-27

Kelly CR, Wu GD, LA Laine (2021)

Response to: Olesen SW, "Fecal microbiota transplantation "donor effects" are not clinically relevant for Clostridioides difficile infection.".

RevDate: 2021-02-28

Staley C, Halaweish H, Graiziger C, et al (2021)

Lower endoscopic delivery of freeze-dried intestinal microbiota results in more rapid and efficient engraftment than oral administration.

Scientific reports, 11(1):4519.

Fecal microbiota transplantation (FMT) is a highly effective treatment for recurrent Clostridioides difficile infection (rCDI). However, standardization of FMT products is essential for its broad implementation into clinical practice. We have developed an oral preparation of freeze-dried, encapsulated microbiota, which is ~ 80% clinically effective, but results in delayed engraftment of donor bacteria relative to administration via colonoscopy. Our objective was to measure the engraftment potential of freeze-dried microbiota without the complexity of variables associated with oral administration. We compared engraftment of identical preparations and doses of freeze-dried microbiota following colonoscopic (9 patients) versus oral administration (18 patients). Microbiota were characterized by sequencing of the 16S rRNA gene, and engraftment was determined using the SourceTracker algorithm. Oligotyping analysis was done to provide high-resolution patterns of microbiota engraftment. Colonoscopic FMT was associated with greater levels of donor engraftment within days following the procedure (ANOVA P = 0.035) and specific increases in the relative abundances of donor Lachnospiraceae, Bacteroidaceae, and Porphyromonadaceae (P ≤ 0.033). Lower relative abundances of Bacteroidaceae, Lachnospiraceae, and Ruminococcaceae families were associated with clinical failures. These results suggest that further optimization of oral capsule FMT may improve its engraftment efficiency and clinical efficacy.

RevDate: 2021-03-24
CmpDate: 2021-03-24

Kao D, Wong K, Franz R, et al (2021)

The effect of a microbial ecosystem therapeutic (MET-2) on recurrent Clostridioides difficile infection: a phase 1, open-label, single-group trial.

The lancet. Gastroenterology & hepatology, 6(4):282-291.

BACKGROUND: Faecal microbiota transplantation (FMT) is highly effective for recurrent Clostridioides difficile infection but has inherent risks. Microbial Ecosystem Therapeutic 2 (MET-2) is an oral encapsulated formulation of 40 lyophilised bacterial species initially isolated from stool of a healthy donor, but subsequently manufactured independently of donors, eliminating potential risks introduced by changes in donor health. The aim of this study was to determine MET-2 activity, safety, and tolerability.

METHODS: This phase 1, open-label, single-group feasibility study was done in Alberta, Canada. The main inclusion criteria were mild to moderate C difficile infection and at least one episode of C difficile infection recurrence (ie, two episodes of C difficile infection) within 12 months. Initial daily treatment was ten oral capsules for 2 days, then three capsules for 8 days. If C difficile infection recurred, a higher dose was offered: 20 capsules for 2 days, then three capsules for 8 days. Patients were followed for adverse events and C difficile infection recurrence up to day 130. The primary outcome was absence of C difficile infection recurrence (fewer than three unformed bowel movements in 24 h persisting for at least 2 days) at day 40 by intention-to-treat analysis. Secondary outcomes were mortality or hospitalisation due to C difficile infection, infections attributed to treatment, nausea, abdominal pain, vomiting, or diarrhoea during treatment, quality of life (C difficile Health Related Quality of Life Questionnaire) before and after treatment, and engrafted MET-2 bacteria in patient stool. Absence of C difficile infection recurrence at day 130 was an exploratory outcome. This study is registered with, NCT02865616 FINDINGS: Between Sept 19, 2018, and Feb 28, 2020, we enrolled 19 adult patients with at least two episodes of mild to moderate C difficile infection (median age 65 years [IQR 56-67]; 12 women [63%], seven men [37%]). Recurrent C difficile infection was absent at day 40 in 15 (79%) of 19 patients after initial treatment, increasing to 18 (95%) 40 days after retreatment. No mortality associated with C difficile infection, infections associated with MET-2 treatment, or other serious adverse events were observed. The most common self-limited, mild to moderate symptoms reported during treatment were diarrhoea in 12 (63%) of 19 patients and abdominal cramps in 12 (63%). After MET-2 treatment, quality of life improved significantly, as did alpha diversity in stool microbial composition (p=1·93×10-6). MET-2 associated taxa were found in greater abundance in most patients after treatment compared with baseline. 16 (84%) of 19 patients did not have recurrence of C difficile infection by day 130.

INTERPRETATION: MET-2 appears to be safe, efficacious, and well tolerated among patients with recurrent C difficile infection. Results must be validated in controlled studies.

FUNDING: NuBiyota.

RevDate: 2021-02-26

Du D, Tang W, Zhou C, et al (2021)

Fecal Microbiota Transplantation Is a Promising Method to Restore Gut Microbiota Dysbiosis and Relieve Neurological Deficits after Traumatic Brain Injury.

Oxidative medicine and cellular longevity, 2021:5816837.

Background: Traumatic brain injury (TBI) can induce persistent fluctuation in the gut microbiota makeup and abundance. The present study is aimed at determining whether fecal microbiota transplantation (FMT) can rescue microbiota changes and ameliorate neurological deficits after TBI in rats.

Methods: A controlled cortical impact (CCI) model was used to simulate TBI in male Sprague-Dawley rats, and FMT was performed for 7 consecutive days. 16S ribosomal RNA (rRNA) sequencing of fecal samples was performed to analyze the effects of FMT on gut microbiota. Modified neurological severity score and Morris water maze were used to evaluate neurobehavioral functions. Metabolomics was used to screen differential metabolites from the rat serum and ipsilateral brains. The oxidative stress indices were measured in the brain.

Results: TBI induced significance changes in the gut microbiome, including the alpha- and beta-bacterial diversity, as well as the microbiome composition at 8 days after TBI. On the other hand, FMT could rescue these changes and relieve neurological deficits after TBI. Metabolomics results showed that the level of trimethylamine (TMA) in feces and the level of trimethylamine N-oxide (TMAO) in the ipsilateral brain and serum was increased after TBI, while FMT decreased TMA levels in the feces, and TMAO levels in the ipsilateral brain and serum. Antioxidant enzyme methionine sulfoxide reductase A (MsrA) in the ipsilateral hippocampus was decreased after TBI but increased after FMT. In addition, FMT elevated SOD and CAT activities and GSH/GSSG ratio and diminished ROS, GSSG, and MDA levels in the ipsilateral hippocampus after TBI.

Conclusions: FMT can restore gut microbiota dysbiosis and relieve neurological deficits possibly through the TMA-TMAO-MsrA signaling pathway after TBI.

RevDate: 2021-03-15

Wang J, Li X, Wu X, et al (2021)

Gut microbiota alterations associated with antibody-mediated rejection after kidney transplantation.

Applied microbiology and biotechnology, 105(6):2473-2484.

Antibody-mediated rejection (AMR) has become the major challenge for kidney transplantation, and the efficacy of existing therapies was limited to prevent AMR. Increasing evidences have demonstrated the link between gut microbiota alterations and allograft outcome. However, there has been no comprehensive analysis to profile the gut microbiota associated with AMR after kidney transplantation. We performed this study to characterize the gut microbiota possibly associated with AMR. Fecal specimens were collected from 24 kidney transplantation recipients with AMR and 29 controls. DNA extracted from the specimens was processed for 16S rRNA gene sequencing using Illumina MiSeq. Gut microbial community of recipients with AMR was significantly different from that of controls based on unweighted (P = 0.001) and weighted (P = 0.02) UniFrac distances, and the bacterial richness (observed species: P = 0.0448; Chao1 index: P = 0.0450; ACE index: P = 0.0331) significantly decreased in the AMR group. LEfSe showed that 1 phylum, 5 classes, 7 families, and 10 genera were increased, whereas 1 class, 2 order, 3 families, and 4 genera were decreased in the AMR group. Specific taxa such as Clostridiales could be potentially used as biomarkers to distinguish the recipients with AMR from the controls (AUC = 0.77). PICRUSt analysis illustrated that 16 functional pathways were with significantly different abundances in the AMR and control groups. Our findings provide a foundation for further investigation on the role of gut microbiota in AMR after kidney transplantation, and potentially support novel diagnostic biomarkers and therapeutic options for AMR. KEY POINTS: • Gut microbial community of kidney recipients with AMR was different from that of controls. • Clostridiales is a potential marker to distinguish recipients with AMR from controls.

RevDate: 2021-02-27

Berland M, Cadiou J, Levenez F, et al (2021)

High engraftment capacity of frozen ready-to-use human fecal microbiota transplants assessed in germ-free mice.

Scientific reports, 11(1):4365.

The number of indications for fecal microbiota transplantation is expected to rise, thus increasing the needs for production of readily available frozen or freeze-dried transplants. Using shotgun metagenomics, we investigated the capacity of two novel human fecal microbiota transplants prepared in maltodextrin-trehalose solutions (abbreviated MD and TR for maltodextrin:trehalose, 3:1, w/w, and trehalose:maltodextrin 3:1, w/w, respectively), to colonize a germ-free born mouse model. Gavage with frozen-thawed MD or TR suspensions gave the taxonomic profiles of mouse feces that best resembled those obtained with the fresh inoculum (Spearman correlations based on relative abundances of metagenomic species around 0.80 and 0.75 for MD and TR respectively), while engraftment capacity of defrosted NaCl transplants most diverged (Spearman correlations around 0.63). Engraftment of members of the family Lachnospiraceae and Ruminoccocaceae was the most challenging in all groups of mice, being improved with MD and TR transplants compared to NaCl, but still lower than with the fresh preparation. Improvement of engraftment of this important group in maintaining health represents a challenge that could benefit from further research on fecal microbiota transplant manufacturing.

RevDate: 2021-02-23

Sheh A (2021)

The Gastrointestinal Microbiota of the Common Marmoset (Callithrix jacchus).

ILAR journal pii:6146828 [Epub ahead of print].

The microbiota is heavily involved in both health and disease pathogenesis, but defining a normal, healthy microbiota in the common marmoset has been challenging. The aim of this review was to systematically review recent literature involving the gastrointestinal microbiome of common marmosets in health and disease. Twelve sources were included in this review. The gut microbiome composition was reviewed across institutions worldwide, and taxonomic shifts between healthy individuals were described. Unlike the human gut microbiome, which is dominated by Firmicutes and Bacteroidetes, the marmoset gut microbiome shows great plasticity across institutions, with 5 different phyla described as dominant in different healthy cohorts. Genera shared across institutions include Anaerobiospirillum, Bacteroides, Bifidobacterium, Collinsella, Fusobacterium, Megamonas, Megasphaera, Phascolarctobacterium, and Prevotella. Shifts in the abundance of Prevotella or Bifidobacterium or invasion by pathogens like Clostridium perfringens may be associated with disease. Changes in microbial composition have been described in healthy and diseased marmosets, but factors influencing the severe changes in microbial composition have not been established. Multi-institutional, prospective, and longitudinal studies that utilize multiple testing methodologies are required to determine sources of variability in the reporting of marmoset microbiomes. Furthermore, methods of microbial manipulation, whether by diet, enrichment, fecal microbiome transplantation, etc, need to be established to modulate and maintain robust and resilient microbiome communities in marmoset colonies and reduce the incidence of idiopathic gastrointestinal disease.

RevDate: 2021-03-17

Rungue M, Melo V, Martins D, et al (2021)

NLRP6-associated host microbiota composition impacts in the intestinal barrier to systemic dissemination of Brucella abortus.

PLoS neglected tropical diseases, 15(2):e0009171.

Brucella abortus is a Gram-negative bacterium responsible for a worldwide zoonotic infection-Brucellosis, which has been associated with high morbidity rate in humans and severe economic losses in infected livestock. The natural route of infection is through oral and nasal mucosa but the invasion process through host gut mucosa is yet to be understood. Studies have examined the role of NLRP6 (NOD-like receptor family pyrin domain-containing-6 protein) in gut homeostasis and defense against pathogens. Here, we investigated the impact of gut microbiota and NLRP6 in a murine model of Ba oral infection. Nlrp6-/- and wild-type (WT) mice were infected by oral gavage with Ba and tissues samples were collected at different time points. Our results suggest that Ba oral infection leads to significant alterations in gut microbiota. Moreover, Nlrp6-/- mice were more resistant to infection, with decreased CFU in the liver and reduction in gut permeability when compared to the control group. Fecal microbiota transplantation from WT and Nlrp6-/- into germ-free mice reflected the gut permeability phenotype from the donors. Additionally, depletion of gut microbiota by broad-spectrum-antibiotic treatment prevented Ba replication in WT while favoring bacterial growth in Nlrp6-/-. Finally, we observed higher eosinophils in the gut and leukocytes in the blood of infected Nlrp6-/- compared to WT-infected mice, which might be associated to the Nlrp6-/- resistance phenotype. Altogether, these results indicated that gut microbiota composition is the major factor involved in the initial stages of pathogen host replication and partially also by the resistance phenotype observed in Nlrp6 -/- mice regulating host inflammation against Ba infection.

RevDate: 2021-03-16

Henson MA (2021)

Computational modeling of the gut microbiota reveals putative metabolic mechanisms of recurrent Clostridioides difficile infection.

PLoS computational biology, 17(2):e1008782.

Approximately 30% of patients who have Clostridioides difficile infection (CDI) will suffer at least one incident of reinfection. While the underlying causes of CDI recurrence are poorly understood, interactions between C. difficile and commensal gut bacteria are thought to play an important role. In this study, an in silico pipeline was used to process 16S rRNA gene amplicon sequence data of 225 stool samples from 93 CDI patients into sample-specific models of bacterial community metabolism. Clustered metabolite production rates generated from post-diagnosis samples generated a high Enterobacteriaceae abundance cluster containing disproportionately large numbers of recurrent samples and patients. This cluster was predicted to have significantly reduced capabilities for secondary bile acid synthesis but elevated capabilities for aromatic amino acid catabolism. When applied to 16S sequence data of 40 samples from fecal microbiota transplantation (FMT) patients suffering from recurrent CDI and their stool donors, the community modeling method generated a high Enterobacteriaceae abundance cluster with a disproportionate large number of pre-FMT samples. This cluster also was predicted to exhibit reduced secondary bile acid synthesis and elevated aromatic amino acid catabolism. Collectively, these in silico predictions suggest that Enterobacteriaceae may create a gut environment favorable for C. difficile spore germination and/or toxin synthesis.

RevDate: 2021-03-04

Pham VT, Fehlbaum S, Seifert N, et al (2021)

Effects of colon-targeted vitamins on the composition and metabolic activity of the human gut microbiome- a pilot study.

Gut microbes, 13(1):1-20.

An increasing body of evidence has shown that gut microbiota imbalances are linked to diseases. Currently, the possibility of regulating gut microbiota to reverse these perturbations by developing novel therapeutic and preventive strategies is being extensively investigated. The modulatory effect of vitamins on the gut microbiome and related host health benefits remain largely unclear. We investigated the effects of colon-delivered vitamins A, B2, C, D, and E on the gut microbiota using a human clinical study and batch fermentation experiments, in combination with cell models for the assessment of barrier and immune functions. Vitamins C, B2, and D may modulate the human gut microbiome in terms of metabolic activity and bacterial composition. The most distinct effect was that of vitamin C, which significantly increased microbial alpha diversity and fecal short-chain fatty acids compared to the placebo. The remaining vitamins tested showed similar effects on microbial diversity, composition, and/or metabolic activity in vitro, but in varying degrees. Here, we showed that vitamins may modulate the human gut microbiome. Follow-up studies investigating targeted delivery of vitamins to the colon may help clarify the clinical significance of this novel concept for treating and preventing dysbiotic microbiota-related human diseases. Trial registration:, NCT03668964. Registered 13 September 2018 - Retrospectively registered,

RevDate: 2021-02-23

Qi R, Zhang Z, Wang J, et al (2021)

Introduction of Colonic and Fecal Microbiota From an Adult Pig Differently Affects the Growth, Gut Health, Intestinal Microbiota and Blood Metabolome of Newborn Piglets.

Frontiers in microbiology, 12:623673.

Microbiota transplantation is a rapid and effective method for changing and reshaping the intestinal microbiota and metabolic profile in humans and animals. This study compared the different influences of the introduction of fecal microbes and colonic microbes from a fat, adult pig in newborn pigs. Both colonic microbiota transplantation (CMT) and fecal microbiota transplantation (FMT) promoted growth and improved gut functions in suckling pigs up to weaning. FMT was more beneficial for body weight gain and body fat deposition in piglets, while CMT was more beneficial for intestinal health and mucosal immunity. 16S rDNA sequence analysis indicated that both CMT and FMT significantly increased the abundances of beneficial or functional bacteria, such as Lactobacillus and Prevotella_2 genera, in the piglets, and reduced the abundances of harmful bacteria, such as Escherichia-Shigella. Blood metabolome analysis showed that transplantation, especially FMT, enhanced lipid metabolism in piglets. In addition, while CMT also changed amino acid metabolism and increased anti-inflammatory metabolites such as 3-indoleacetic acid and 3-indolepropionic acid in piglets, FMT did not. Of note, FMT damaged the intestinal barrier of piglets to a certain extent and increased the levels of inflammatory factors in the blood that are potentially harmful to the health of pigs. Taken together, these results suggested that intestinal and fecal microbiota transplantations elicited similar but different physiological effects on young animals, so the application of microbiota transplantation in animal production requires the careful selection and evaluation of source bacteria.

RevDate: 2021-02-20

Barrow F, Khan S, Fredrickson G, et al (2021)

Microbiota-Driven Activation of Intrahepatic B Cells Aggravates Nonalcoholic Steatohepatitis through Innate and Adaptive Signaling.

Hepatology (Baltimore, Md.) [Epub ahead of print].

BACKGROUND AND AIMS: Nonalcoholic steatohepatitis (NASH) is rapidly becoming the leading cause of liver failure and indication for liver transplantation. Hepatic inflammation is a key feature of NASH but the immune pathways involved in this process are poorly understood. B lymphocytes are cells of the adaptive immune system that are critical regulators of immune responses. However, the role of B cells in the pathogenesis of NASH and the potential mechanisms leading to their activation in the liver are unclear.

APPROACH AND RESULTS: In this study, we report that NASH livers accumulate B cells with elevated pro-inflammatory cytokine secretion and antigen-presentation ability. Single-cell and bulk RNA sequencing of intrahepatic B cells from mice with NASH unveiled a transcriptional landscape that reflects their pro-inflammatory function. Accordingly, B cell-deficiency ameliorated NASH progression and adoptively transferring B cells from NASH livers recapitulates the disease. Mechanistically, B cell activation during NASH involves signaling through the innate adaptor myeloid differentiation primary response protein 88 (MyD88) as B cell-specific deletion of MyD88 reduced hepatic T cell-mediated inflammation and fibrosis, but not steatosis. In addition, activation of intrahepatic B cells implicates B cell receptor signaling, delineating a synergy between innate and adaptive mechanisms of antigen recognition. Furthermore, fecal microbiota transplantation of human NAFLD gut microbiotas into recipient mice promoted the progression of NASH by increasing the accumulation and activation of intrahepatic B cells, suggesting that gut microbial factors drive the pathogenic function of B cells during NASH.

CONCLUSION: Our findings reveal that a gut microbiota-driven activation of intrahepatic B cells leads to hepatic inflammation and fibrosis during the progression of NASH via innate and adaptive immune mechanisms.

RevDate: 2021-02-25

Kazemian N, Ramezankhani M, Sehgal A, et al (2021)

Author Correction: The trans-kingdom battle between donor and recipient gut microbiome influences fecal microbiota transplantation outcome.

Scientific reports, 11(1):4546 pii:10.1038/s41598-021-82644-z.

RevDate: 2021-02-19

Wang B, Zhu S, Liu Z, et al (2021)

Increased Expression of Colonic Mucosal Melatonin in Patients with Irritable Bowel Syndrome Correlated with Gut Dysbiosis.

Genomics, proteomics & bioinformatics pii:S1672-0229(21)00018-8 [Epub ahead of print].

Dysregulation of the gut microbiota/gut hormone axis contributes to the pathogenesis of irritable bowel syndrome (IBS). Melatonin plays a beneficial role in gut motility and immunity. However, altered expression of local mucosal melatonin in IBS and its relationship with the gut microbiota remain unclear. Therefore, we aimed to detect the colonic melatonin levels and microbiota profiles in patients with diarrhea-predominant IBS (IBS-D) and explore their relationship in germ-free (GF) rats and BON-1 cells. Thirty-two IBS-D patients and twenty-eight healthy controls (HC) were recruited. Fecal specimens from IBS-D patients and HC were separately transplanted into GF rats by gavage. The levels of colon mucosal melatonin were assessed by immunohistochemical methods, and fecal microbiota communities were analyzed using 16S rDNA sequencing. The effect of butyrate on melatonin synthesis in BON-1 cells was evaluated by ELISA. Melatonin levels were significantly increased and negatively correlated with visceral sensitivity in IBS-D patients. GF rats inoculated with fecal microbiota from IBS-D patients had high colonic melatonin levels. Butyrate-producing Clostridium cluster XIVa species, such as Roseburia species and Lachnospira species, were positively related to colonic mucosal melatonin expression. Butyrate significantly increased melatonin secretion in BON-1 cells. Increased melatonin expression may be an adaptive protective mechanism in the development of IBS-D. Moreover, some Clostridium cluster XIVa species could increase melatonin expression via butyrate production. Modulation of the gut hormone/gut microbiota axis offers a promising target of interest for IBS in the future.

RevDate: 2021-02-19

Gupta S, Mullish BH, JR Allegretti (2021)

Fecal Microbiota Transplantation: The Evolving Risk Landscape.

The American journal of gastroenterology [Epub ahead of print].

Fecal microbiota transplantation (FMT) has been recommended in clinical guidelines for the treatment of recurrent Clostridioides difficile infection (CDI). However, it is considered investigational by most regulatory agencies. As the adoption of FMT has increased from a small group of CDI experts alone to more widespread use, there has been a corresponding increase in concern regarding potential risk. FMT is largely considered a safe procedure although risks described range from mild gastrointestinal symptoms to serious infection. Currently, there is variability in how "FMT" is characterized specifically regarding testing approach, which, in turn, impacts the risk profile. This has been highlighted by the rare cases of multidrug-resistant organisms, Shiga toxin-producing Escherichia and enteropathogenic E. coli, recently reported, where these organisms were not screened. These cases have prompted additional screening mandates from the US Food and Drug Administration (FDA), which has maintained its policy of enforcement discretion for the use of FMT for CDI not responding to standard therapy. Here, we examine the evolving risk landscape of FMT.

RevDate: 2021-03-09

Zhang LT, Westblade LF, Iqbal F, et al (2021)

Gut microbiota profiles and fecal beta-glucuronidase activity in kidney transplant recipients with and without post-transplant diarrhea.

Clinical transplantation [Epub ahead of print].

Post-transplant diarrhea is a common complication after solid organ transplantation and is frequently attributed to the widely prescribed immunosuppressant mycophenolate mofetil (MMF). Given recent work identifying the relationship between MMF toxicity and gut bacterial β-glucuronidase activity, we evaluated the relationship between gut microbiota composition, fecal β-glucuronidase activity, and post-transplant diarrhea. We recruited 97 kidney transplant recipients and profiled the gut microbiota in 273 fecal specimens using 16S rRNA gene sequencing. We further characterized fecal β-glucuronidase activity in a subset of this cohort. Kidney transplant recipients with post-transplant diarrhea had decreased gut microbial diversity and decreased relative gut abundances of 12 genera when compared to those without post-transplant diarrhea (adjusted p value < .15, Wilcoxon rank sum test). Among the kidney transplant recipients with post-transplant diarrhea, those with higher fecal β-glucuronidase activity had a more prolonged course of diarrhea (≥7 days) compared to patients with lower fecal β-glucuronidase activity (91% vs 40%, p = .02, Fisher's exact test). Our data reveal post-transplant diarrhea as a complex phenomenon with decreased gut microbial diversity and commensal gut organisms. This study further links commensal bacterial metabolism with an important clinical outcome measure, suggesting fecal β-glucuronidase activity could be a novel biomarker for gastrointestinal-related MMF toxicity.


ESP Quick Facts

ESP Origins

In the early 1990's, Robert Robbins was a faculty member at Johns Hopkins, where he directed the informatics core of GDB — the human gene-mapping database of the international human genome project. To share papers with colleagues around the world, he set up a small paper-sharing section on his personal web page. This small project evolved into The Electronic Scholarly Publishing Project.

ESP Support

In 1995, Robbins became the VP/IT of the Fred Hutchinson Cancer Research Center in Seattle, WA. Soon after arriving in Seattle, Robbins secured funding, through the ELSI component of the US Human Genome Project, to create the original ESP.ORG web site, with the formal goal of providing free, world-wide access to the literature of classical genetics.

ESP Rationale

Although the methods of molecular biology can seem almost magical to the uninitiated, the original techniques of classical genetics are readily appreciated by one and all: cross individuals that differ in some inherited trait, collect all of the progeny, score their attributes, and propose mechanisms to explain the patterns of inheritance observed.

ESP Goal

In reading the early works of classical genetics, one is drawn, almost inexorably, into ever more complex models, until molecular explanations begin to seem both necessary and natural. At that point, the tools for understanding genome research are at hand. Assisting readers reach this point was the original goal of The Electronic Scholarly Publishing Project.

ESP Usage

Usage of the site grew rapidly and has remained high. Faculty began to use the site for their assigned readings. Other on-line publishers, ranging from The New York Times to Nature referenced ESP materials in their own publications. Nobel laureates (e.g., Joshua Lederberg) regularly used the site and even wrote to suggest changes and improvements.

ESP Content

When the site began, no journals were making their early content available in digital format. As a result, ESP was obliged to digitize classic literature before it could be made available. For many important papers — such as Mendel's original paper or the first genetic map — ESP had to produce entirely new typeset versions of the works, if they were to be available in a high-quality format.

ESP Help

Early support from the DOE component of the Human Genome Project was critically important for getting the ESP project on a firm foundation. Since that funding ended (nearly 20 years ago), the project has been operated as a purely volunteer effort. Anyone wishing to assist in these efforts should send an email to Robbins.

ESP Plans

With the development of methods for adding typeset side notes to PDF files, the ESP project now plans to add annotated versions of some classical papers to its holdings. We also plan to add new reference and pedagogical material. We have already started providing regularly updated, comprehensive bibliographies to the ESP.ORG site.

Electronic Scholarly Publishing
961 Red Tail Lane
Bellingham, WA 98226

E-mail: RJR8222 @

Papers in Classical Genetics

The ESP began as an effort to share a handful of key papers from the early days of classical genetics. Now the collection has grown to include hundreds of papers, in full-text format.

Digital Books

Along with papers on classical genetics, ESP offers a collection of full-text digital books, including many works by Darwin (and even a collection of poetry — Chicago Poems by Carl Sandburg).


ESP now offers a much improved and expanded collection of timelines, designed to give the user choice over subject matter and dates.


Biographical information about many key scientists.

Selected Bibliographies

Bibliographies on several topics of potential interest to the ESP community are now being automatically maintained and generated on the ESP site.

ESP Picks from Around the Web (updated 07 JUL 2018 )