Dynamics of the Gut Mycobiome in Patients With Ulcerative Colitis.

BACKGROUND & AIMS: Intestinal fungi have been implicated in the pathogenesis of ulcerative colitis (UC). However, it remains unclear if fungal composition is altered during active versus quiescent disease. METHODS: We analyzed clinical and metagenomic data from the Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease (SPARC IBD), available via the IBD Plexus Program of the Crohn's & Colitis Foundation. We evaluated the fungal composition of fecal samples from 421 patients with UC during clinical activity and remission. Within a longitudinal subcohort (n = 52), we assessed for dynamic taxonomic changes across alterations in clinical activity over time. We examined if fungal amplicon sequence variants and fungal-bacterial relationships were altered during activity versus remission. Finally, we classified activity in UC using a supervised machine learning random forest model trained on fungal abundance data. RESULTS: During clinical activity, the relative abundance of genus Candida was increased 3.5-fold (P-adj < 1 × 10-4) compared with during remission. Patients with longitudinal reductions in clinical activity demonstrated parallel reductions in Candida relative abundance (P < .05). Candida relative abundance correlated with Parabacteroides diastonis, Faecalibacterium prausnitzii, and Bacteroides dorei relative abundance (P < .05) during remission; however, these correlations were disrupted during activity. Fungal abundance data successfully classified patients with active or quiescent UC (area under the curve ∼0.80), with Candida relative abundance critical to the success of the model. CONCLUSIONS: Clinical activity in UC is associated with an increased relative abundance of Candida, cross-sectionally and dynamically over time. The role of fecal Candida as a target for therapeutics in UC should be evaluated.

Cultured fecal microbial community and its impact as fecal microbiota transplantation treatment in mice gut inflammation.

The fecal microbiome is identical to the gut microbial communities and provides an easy access to the gut microbiome. Therefore, fecal microbial transplantation (FMT) strategies have been used to alter dysbiotic gut microbiomes with healthy fecal microbiota, successfully alleviating various metabolic disorders, such as obesity, type 2 diabetes, and inflammatory bowel disease (IBD). However, the success of FMT treatment is donor-dependent and variations in gut microbes cannot be avoided. This problem may be overcome by using a cultured fecal microbiome. In this study, a human fecal microbiome was cultured using five different media; growth in brain heart infusion (BHI) media resulted in the highest microbial community cell count. The microbiome (16S rRNA) data demonstrated that the cultured microbial communities were similar to that of the original fecal sample. Therefore, the BHI-cultured fecal microbiome was selected for cultured FMT (cFMT). Furthermore, a dextran sodium sulfate (DSS)-induced mice-IBD model was used to confirm the impact of cFMT. Results showed that cFMT effectively alleviated IBD-associated symptoms, including improved gut permeability, restoration of the inflamed gut epithelium, decreased expression of pro-inflammatory cytokines (IFN-γ, TNF-α, IL-1, IL-6, IL-12, and IL-17), and increased expression of anti-inflammatory cytokines (IL-4 and IL-10). Thus, study's findings suggest that cFMT can be a potential alternative to nFMT. KEY POINTS: • In vitro fecal microbial communities were grown in a batch culture using five different media. • Fecal microbial transplantation was performed on DSS-treated mice using cultured and normal fecal microbes. • Cultured fecal microbes effectively alleviated IBD-associated symptoms.

A comprehensive review of the multifaceted role of the microbiota in human pancreatic carcinoma.

Pancreatic carcinoma is associated with one of the worst clinical outcomes throughout the globe because of its aggressive, metastatic, and drug-resistant nature. During the past decade, several studies have shown that oral, gut, and tumor microbiota play a critical role in the modulation of metabolism and immune responses. Growing pieces of evidence have proved beyond a doubt that the microbiota has a unique ability to influence the tumor microenvironment as well as the metabolism of chemotherapeutic agents or drugs. Given this, microbiota, known as the ecological community of microorganisms, stands to be an avenue of quality research. In this review, we provide detailed and critical information on the role of oral, gut, and pancreatic microbiota disruptions in the development of pancreatic carcinoma. Moreover, we comprehensively discuss the different types of microbiota, their potential role, and mechanism associated with pancreatic carcinoma. The microbiome provides the unique opportunity to enhance the effectiveness of chemotherapeutic agents and immunotherapies for pancreatic cancer by maintaining the right type of microbiota and holds a promising future to enhance the clinical outcomes of patients with pancreatic carcinoma.

The Intestinal Microbiome and the Metabolic Syndrome-How Its Manipulation May Affect Metabolic-Associated Fatty Liver Disease (MAFLD).

Metabolic-associated fatty liver disease (MAFLD) is now the predominant liver disease worldwide consequent to the epidemic of obesity. The intestinal microbiome (IM), consisting of the bacteria, fungi, archaea, and viruses residing in the gastrointestinal tract, plays an important role in human metabolism and preserving the epithelial barrier function. Disturbances in the IM have been shown to influence the development and progression of MAFLD and play a role in the development of metabolic syndrome (MS). The main treatment for MAFLD involves lifestyle changes, which also influence the IM. Manipulation of the IM by fecal microbial transplantation (FMT) has been approved for the treatment of recurrent Closteroides difficile infection. This may be administered by endoscopic administration from the lower or upper GI tract. Other methods of administration include nasogastric tube, enema, and oral capsules of stool from healthy donors. In this narrative review, we elaborate on the role of the IM in developing MS and MAFLD and on the current experience with IM modulation by FMT on MAFLD.

Donor selection for fecal bacterial transplantation and its combined effects with inulin on early growth and ileal development in chicks.

AIMS: To select the best donor and investigate its combined effects with inulin on growth performance, and ileal health of chicks. METHODS AND RESULTS: The chicks (Hy-line Brown) were treated with fecal microbiota suspension from different breeder hens to select the best donor. Treatment with fecal microbiota transplantation (FMT) alone or in combination with inulin resulted in improvement in gut microbiome in chicks. The organ indexes were improved on day 7, especially the bursa of fabricius index (P < 0.05). On day 14, immune performance, ileal morphology, and barrier were improved, and simultaneously, the concentration of short-chain fatty acids was also increased. In addition, for the expression of ileal barrier-related genes, Anaerofustis and Clostridium were positively correlated with them (P < 0.05), Blautia, Prevotella, Veillonella, and Weissella showed a negative correlation (P < 0.05), and RFN20 showed a positive correlation with gut morphology (P < 0.05). CONCLUSION: Combination of homologous FMT and inulin promoted early growth and intestinal health of chicks.

The interplay of obesity, gut microbiome and diet in the immune check point inhibitors therapy era.

Immunotherapy has recently emerged as a promising treatment option for many patients, revolutionizing the established therapeutic approach against cancer. Immune checkpoints inhibitors (ICIs) have demonstrated clinical activity in a wide spectrum of malignancies; however, only a minority of patients exhibit durable responses. This response heterogeneity may be partly attributed to host related factors, such as body mass index (BMI), diet and gut microbiome, that have recently emerged as strong influences in ICI responsiveness. Obesity not only directly impacts on cancer promotion but also on the immune homeostasis and the elimination, equilibrium, and escape phases of immune-editing. Paradoxically, emerging clinical data indicate that obese patients are benefited from ICI therapy when compared to normal BMI cancer patients. Interestingly, strong evidence supports the role of the microbiome in cancer immunotherapy, with several recent animal, translational/hybrid and clinical studies demonstrating its influence in the response to ICIs across several malignancies. Noteworthy, nutrition, through its well-established links to obesity, microbiome composition and oncogenicity, may contribute towards leveraging its effects in favor of cancer patients alongside with gold standard treatments. The aim of this review is to delineate the associations of ICIs with obesity, host microbiome and nutrition, and to explore how these factors can be effectively leveraged in enhancing the effectiveness of immunotherapy. More specific aims include the determination of how patients with obesity are differentially affected by ICI therapy; how the host microbiome affects response to ICIs; and how the microbiome itself is modulated by obesity and nutrition. In conclusion, immunometabolism, microbiome and nutrition research present the potential to offer unique tools in unleashing ICIs full potential; providing host-derived, actionable, modifiable targets directly associated with therapeutic outcomes that can be efficiently leveraged. Future efforts, provided that they adhere to robustness of methodology, can facilitate transferring these findings, from bench to bedside.

Novel approaches to intervene gut microbiota in the treatment of chronic liver diseases.

Recent investigations of gut microbiota have contributed to understanding of the critical role of microbial community in pathophysiology. Dysbiosis not only causes disturbance directly to the gastrointestinal tract but also affects the liver through gut-liver axis. Various types of dysbiosis have been documented in alcoholic liver disease (ALD), nonalcoholic fatty liver disease, autoimmune hepatitis (AIH), primary sclerosing cholangitis, and may be crucial for the initiation, progression, or deterioration to end-stage liver disease. A few microbial species have been identified as the causal factors leading to these chronic illnesses that either do not have clear etiologies or lack effective treatment. Notably, cytolysin-producing Enterococcus faecalis, Klebsiella pneumoniae and Enterococcus gallinarum were defined for ALD, NASH, and AIH, respectively. These groundbreaking discoveries drive a rapid development in innovative therapeutics, such as fecal microbial transplantation and implementation of specific bacteriophages in addition to prebiotics, probiotics, or synbiotics for intervention of dysbiosis. Although most emerging interventions are in preclinical development or early clinical trials, a better delineation of specific dysbiosis in these disorders at metabolic, immunogenic, or molecular levels in establishing particular causal effects aids in modulating or correcting the microbial community which is the part of daily life for human being.

Comprehensive bibliometric and visualized analysis of research on fecal microbial transplantation published from 2000 to 2021.

BACKGROUND: Fecal microbial transplantation has emerged in recent years as a method of treating disease by rebuilding the intestinal flora. However, few bibliometric analyses have systematically studied this area of research. We aimed to use bibliometric analysis to visualize trends and topical research in fecal microbial transplantation to help provide insight into future trends in clinical and basic research. MATERIALS AND METHODS: Articles and reviews related to fecal microbial transplantation were collected from the Web of Science Core Collection. Significant information associated with this field was visually analyzed by using Biblioshiny and CtieSpace software. RESULTS: A total of 3144 articles and overviews were included. The number of publications related to fecal microbial transplantation significantly increased yearly. These publications mainly came from 100 countries, led by the US and China, and 521 institutions. The most prolific and influential author is KHORUTS A. The main disciplines and application fields of fecal microbial transplantation included molecular /biology/immunology and medicine/clinical medicine, and the research foundation of fecal microbial transplantation was molecular /biology/genetics and health/nursing/medicine. An alluvial flow visualization showed several landmark articles. New developments were identified in terms of reference and keyword citation bursts. Data analysis showed that different FMT preparation and delivery methods gradually appeared as research hotspots. The main research keywords in the last 3 years were chain fatty acids, Akkermansia muciniphila, and insulin sensitivity, other keywords were current and developing research fields. CONCLUSION: Research on fecal microbial transplantation is flourishing and many new applications of fecal microbial transplantation are emerging. Microbial metabolites such as short-chain fatty acids and the microbiota-gut-brain axis have become the focus of current research and are future research trends.

Unravelling the potential of gut microbiota in sustaining brain health and their current prospective towards development of neurotherapeutics.

Increasing incidences of neurological disorders, such as Parkinson's disease (PD), multiple sclerosis (MS), Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS) are being reported, but an insight into their pathology remains elusive. Findings have suggested that gut microbiota play a major role in regulating brain functions through the gut-brain axis. A unique bidirectional communication between gut microbiota and maintenance of brain health could play a pivotal role in regulating incidences of neurodegenerative diseases. Contrarily, the present life style with changing food habits and disturbed circadian rhythm may contribute to gut homeostatic imbalance and dysbiosis leading to progression of several neurological disorders. Therefore, dysbiosis, as a primary factor behind intestinal disorders, may also augment inflammation, intestinal and blood-brain barrier permeability through microbiota-gut-brain axis. This review primarily focuses on the gut-brain axis functions, specific gut microbial population, metabolites produced by gut microbiota, their role in regulating various metabolic processes and role of gut microbiota towards development of neurodegenerative diseases. However, several studies have reported a decrease in abundance of a specific gut microbial population and a corresponding increase in other microbial family, with few findings revealing some contradictions. Reports also showed that colonization of gut microbiota isolated from patients suffering from neurodegenerative disease leads to the development of enhance pathological outcomes in animal models. Hence, a systematic understanding of the dominant role of specific gut microbiome towards development of different neurodegenerative diseases could possibly provide novel insight into the use of probiotics and microbial transplantation as a substitute approach for treating/preventing such health maladies.

Gut microbiota in chronic inflammatory disorders: A focus on pediatric inflammatory bowel diseases and juvenile idiopathic arthritis.

The gut microbiota is integral to human health, including maintaining the delicate balance between tolerance and protection against potentially harmful pathogens. A growing body of evidence implicates the intestinal microbiome in immune-mediated inflammatory disorders; these data span the spectrum from genetic and environmental disease risk factors, to animal studies (particularly germ-free and gnotobiotic models) and human studies, including evidence of dysbiosis in diseased individuals compared to healthy populations. In this review, we summarize both animal and human data supporting a link between the gut microbiota and inflammatory bowel diseases (IBD) and systemic inflammatory arthritis, as models for chronic inflammatory disorders, while offering a pediatric focus (pediatric IBD and juvenile idiopathic arthritis). We discuss relevant mechanisms related to the crosstalk between the gut microbiota and the innate and adaptive immune system. We close with a brief discussion of emerging microbe-altering interventions, including fecal microbial transplantation and its immunologic effects.

Comorbid status and the faecal microbial transplantation failure in treatment of recurrent Clostridioides difficile infection - pilot prospective observational cohort study.

BACKGROUND: Faecal microbial transplantation (FMT) is currently the most effective treatment of recurrent Clostridioides difficile infection (CDI). However, up to 20% of patients experience further recurrences after single FMT. The mechanisms that lead to FMT failure and its risk factors are poorly understood. Comorbidity is one of the risk factors of the failure of standard antibiotic therapy of recurrent CDI. It is not known if comorbidity is also associated with the risk of FMT failure. METHODS: We conducted a prospective observational cohort study in order to elucidate if comorbid status is associated with FMT failure. Patients with microbiologically proven recurrent CDI were recruited and underwent FMT via retention enema. Patients were followed up for 12 weeks after FMT for signs and symptoms of CDI recurrence. Single FMT failure was defined as recurrence of diarrhoea and a positive stool test for the presence of C. difficile antigen or toxin at any time point during the 12 weeks of follow-up. We assessed the association of single FMT failure with possible manageable and unmanageable risk factors. As a surrogate of comorbid status, we used Charlson Comorbidity Index (CCI) ≥ 7. RESULTS: A total of 60 patients that underwent single FMT (34 women, 26 men) were included in the study. Overall, 15 patients (25%) experienced single FMT failure. 24 patients (40%) had CCI ≥ 7, and 45.0% patients with CCI ≥ 7 experienced failure of single FMT. Patients who experienced single FMT failure had a significantly higher CCI and significantly lower albumin concentration as compared to patients who experienced single FMT success. There was no difference in age, C-reactive protein concentration, leukocyte count and time from FMT to first defecation. In multivariate analysis, CCI ≥ 7 was positively associated with the failure of single FMT. Analysis was controlled for sex, age, time from FMT to first defecation, concomitant PPI therapy, severe CDI, hospital-acquired infection and albumin concentration. CONCLUSIONS: Comorbid status surrogated by CCI is positively associated with the failure of single FMT in the treatment of recurrent CDI.

Fecal microbiota transplantation improves metabolism and gut microbiome composition in db/db mice.

Fecal microbiota transplantation (FMT) has become an effective strategy to treat metabolic diseases, including type 2 diabetes mellitus (T2DM). We previously reported that the intestinal microbiome had significant difference between individuals with normal glucose tolerance and T2DM in Chinese Kazak ethnic group. In this study, we investigated the effects of transplanted fecal bacteria from Kazaks with normal glucose tolerance (KNGT) in db/db mice. The mice were treated with 0.2 mL of fecal bacteria solution from KNGT daily for 10 weeks. We showed that the fecal bacteria from KNGT successfully colonized in the intestinal tract of db/db mice detected on day 14. In the FMT-treated db/db mice, the levels of fasting blood glucose, postprandial glucose, total cholesterol, triglyceride, and low-density lipoprotein-cholesterol were significantly downregulated, whereas high-density lipoprotein-cholesterol levels were upregulated. In the FMT-treated db/db mice, Desulfovibrio and Clostridium coccoides levels in gut were significantly decreased, but the fecal levels of Akkermansia muciniphila and colon histone deacetylase-3 (HDAC3) protein expression were increased. At 8 weeks, both intestinal target bacteria and HDAC3 were correlated with glycolipid levels; Akkermansia muciniphila level was positively correlated with HDAC3 protein expression (r = +0.620, P = 0.037). Our results suggest that fecal bacteria from KNGT could potentially be used to treat diabetic patients.

Should We Fiddle with Gut Microbiome in Critically Ill?

The gut that we took for granted in the critically ill, as just a conduit for food passage has over the decade or so shown us that it is an active endocrine and exocrine organ with over 40 trillion microorganisms living commensally within it. This cosmos of microorganisms that is called the gut microbiome comprises roughly 1,000 different species and put together is more DNA than the entire human genome. Under normal circumstances, in a healthy individual multiple elements of the gut viz intestinal epithelium, gut barrier function, the microbiomes, all put together offer protection against infection and this is crucial in maintenance of health. Any change to the norm, be it in the form of surgical interventions, the introduction of medications, or the pathophysiological effects of systemic disease leads to a 360° alteration in this finely construed ecosystem leading to devastating effects that go beyond the boundaries of the gut itself. Intestinal epithelium helps to absorb nutrients as well as acts as the coordinator of mucosal immunity (first line of immune defense). During ill health, gut epithelial apoptosis occurs, alterations happen in the tight epithelial junctions leading to loss of gut barrier function and loss of the mucosal immunity leading to mucosal damage and hyperpermeability. Lastly, the microbiome is transformed into a pathobiome, with resultant increase in pathogenic bacteria and induction of virulence in commensal gut bacteria. Multiple organ damage starts to set in, caused by toxins leaving the intestine via both portal blood flow and mesenteric lymph. This review article traces the gut microbiomic ecology in health and sickness, modern tools that are used to manipulate gut microbiome in the search for the prevention and treatment of critical illness and will explore if appropriate manipulation of gut microbiome can influence or modulate the course of critical illness. How to cite this article: Venkatachalam B, Abraham BK. Should We Fiddle with Gut Microbiome in Critically Ill? Indian J Crit Care Med 2020;24(Suppl 4):S211-S214.

Probiotic Use in Equine Gastrointestinal Disease.

Probiotics are commonly used in human and veterinary medicine due to their postulated positive effects on overall and specifically gastrointestinal health. Although some beneficial effects have been shown in several human diseases, a general beneficial effect of probiotics is currently not supported. In horses, well-designed studies to date are few, results are conflicting, and the effects of probiotics are questionable. Adverse effects are rare; however, intestinal adverse effects (diarrhea) have been reported in foals. Quality control of over-the-counter probiotics is not tightly regulated, and labels often do not reflect the content.

Targeting the gut-liver axis in liver disease.

The gut-liver axis is widely implicated in the pathogenesis of liver diseases, where it is increasingly the focus of clinical research. Recent studies trialling an array of therapeutic and preventative strategies have yielded promising results. Considering these strategies, the armamentarium for targeting the gut-liver axis will continue to expand. Further clinical trials, translated from our current knowledge of the gut-liver axis, promise an exciting future in liver treatment.

Gut Microbiome and Polycystic Ovary Syndrome: Interplay of Associated Microbial-Metabolite Pathways and Therapeutic Strategies.

Polycystic ovary syndrome (PCOS) is a multifaceted disease with an intricate etiology affecting reproductive-aged women. Despite attempts to unravel the pathophysiology, the molecular mechanism of PCOS remains unknown. There are no effective or suitable therapeutic strategies available to ameliorate PCOS; however, the symptoms can be managed. In recent years, a strong association has been found between the gut microbiome and PCOS, leading to the formulation of novel ideas on the genesis and pathological processes of PCOS. Further, gut microbiome dysbiosis involving microbial metabolites may trigger PCOS symptoms via many mechanistic pathways including those associated with carbohydrates, short-chain fatty acids, lipopolysaccharides, bile acids, and gut-brain axis. We present the mechanistic pathways of PCOS-related microbial metabolites and therapeutic opportunities available to treat PCOS, such as prebiotics, probiotics, and fecal microbiota therapy. In addition, the current review highlights the emerging treatment strategies available to alleviate the symptoms of PCOS.

Microbiome 2.0: lessons from the 2024 Gut Microbiota for Health World Summit.

This Meeting Summary highlights the key insights from the 12th meeting of the Gut Microbiota for Health World Summit, held in Washington, DC, organized by the American Gastroenterological Association (AGA) and the European Society of Neurogastroenterology and Motility (ESNM). Through a 2-day series of plenary sessions, workshops, a poster session, and live discussions involving thought leaders, physicians, researchers, and representatives from the Food and Drug Administration and the pharmaceutical industry, the conference attendees focused on the strategies and challenges in developing microbiome-based therapies to prevent and treat human disease. The conference highlighted progress in the field, including the recently successful introduction of 2 new fecal microbial transplantation-based products into the clinical setting, and the continuing development of next-generation probiotics. However, to continue to advance microbiome-directed treatments, three key themes emerged during the meeting, including (1) better methods to identify actionable targets in the microbiome (2) developing effective strategies to manipulate the microbiome (3) aligning microbiome-based therapies with existing treatment paradigms in the real world.

Microecological regulation in HCC therapy: Gut microbiome enhances ICI treatment.

The exploration of the complex mechanisms of cancer immunotherapy is rapidly evolving worldwide, and our focus is on the interaction of hepatocellular carcinoma (HCC) with immune checkpoint inhibitors (ICIs), particularly as it relates to the regulatory role of the gut microbiome. An important basis for the induction of immune responses in HCC is the presence of specific anti-tumor cells that can be activated and reinforced by ICIs, which is why the application of ICIs results in sustained tumor response rates in the majority of HCC patients. However, mechanisms of acquired resistance to immunotherapy in unresectable HCC result in no long-term benefit for some patients. The significant heterogeneity of inter-individual differences in the gut microbiome in response to treatment with ICIs makes it possible to target modulation of specific gut microbes to assist in augmenting checkpoint blockade therapies in HCC. This review focuses on the complex relationship between the gut microbiome, host immunity, and HCC, and emphasizes that manipulating the gut microbiome to improve response rates to cancer ICI therapy is a clinical strategy with unlimited potential.

Intestinal microecological transplantation for a patient with chronic radiation enteritis: A case report.

BACKGROUND: The gut microbiota is strongly associated with radiation-induced gut damage. This study aimed to assess the effectiveness and safety of intestinal microecological transplantation for treating patients with chronic radiation enteritis. CASE SUMMARY: A 64-year-old female with cervical cancer developed abdominal pain, diarrhea, and blood in the stool 1 year after radiotherapy. An electronic colonoscopy was performed to diagnose chronic radiation enteritis. Two courses of intestinal microecological transplantation and full-length 16S rRNA microbiological analysis were performed. The patient experienced short- and long-term relief from symptoms without adverse effects. Whole 16S rRNA sequencing revealed significant differences in the intestinal flora's composition between patient and healthy donors. Pathogenic bacteria, such as Escherichia fergusonii and Romboutsia timonensis, were more in the patient. Beneficial bacteria such as Faecalibacterium prausnitzii, Fusicatenibacter saccharivorans, Ruminococcus bromii, and Bifidobacterium longum were more in the healthy donors. Intestinal microbiota transplantation resulted in a significant change in the patient's intestinal flora composition. The composition converged with the donor's flora, with an increase in core beneficial intestinal bacteria, such as Eubacterium rectale, and a decrease in pathogenic bacteria. Changes in the intestinal flora corresponded with the patients' alleviating clinical symptoms. CONCLUSION: Intestinal microecological transplantation is an effective treatment for relieving the clinical symptoms of chronic radiation enteritis by altering the composition of the intestinal flora. This study provides a new approach for treating patients with chronic radiation enteritis.