[Chinese expert consensus on the clinical diagnosis and treatment of gut microecology in chronic constipation (2024 edition)].

Chronic constipation is one of the common gastrointestinal disorders, with an incidence rate that is gradually increasing yearly and becoming an important chronic disease that affects people's health and quality of life. In recent years, significant progress has been made in the basic and clinical research of chronic constipation, especially the gut microbiota therapy methods have received increasing attention. Therefore, under the initiative of the Parenteral and Enteral Nutrition Branch of the Chinese Medical Association, Chinese Society for the Promotion of Human Health Science and Technology, and Committee on Gut Microecology and Fecal Microbiota Transplantation, experts from relevant fields in China have been organized to establish the "Chinese Expert Consensus on the Clinical Diagnosis and Treatment of Gut Microecology in Chronic Constipation (2024 Edition)" committee. Focusing on the dysbiosis of gut microbiota, the indications for gut microbiota therapy, and the protocols for fecal microbiota transplantation, 16 consensus opinions were proposed based on the review of domestic and international literature and the clinical experience of experts, aiming to standardize the clinical application of gut microbiota in chronic constipation.

Application of Microbiome-Based Therapies in Chronic Respiratory Diseases.

The application of microbiome-based therapies in various areas of human disease has recently increased. In chronic respiratory disease, microbiome-based clinical applications are considered compelling options due to the limitations of current treatments. The lung microbiome is ecologically dynamic and affected by various conditions, and dysbiosis is associated with disease severity, exacerbation, and phenotype as well as with chronic respiratory disease endotype. However, it is not easy to directly modulate the lung microbiome. Additionally, studies have shown that chronic respiratory diseases can be improved by modulating gut microbiome and administrating metabolites. Although the composition, diversity, and abundance of the microbiome between the gut and lung are considerably different, modulation of the gut microbiome could improve lung dysbiosis. The gut microbiome influences that of the lung via bacterial-derived components and metabolic degradation products, including short-chain fatty acids. This phenomenon might be associated with the cross-talk between the gut microbiome and lung, called gut-lung axis. There are multiple alternatives to modulate the gut microbiome, such as prebiotics, probiotics, and postbiotics ingestion and fecal material transplantation. Several studies have shown that high-fiber diets, for example, present beneficial effects through the production of short-chain fatty acids. Additionally, genetically modified probiotics to secrete some beneficial molecules might also be utilized to treat chronic respiratory diseases. Further studies on microbial modulation to regulate immunity and potentiate conventional pharmacotherapy will improve microbiome modulation techniques, which will develop as a new therapeutic area in chronic respiratory diseases.

Changes in the Progression of Chronic Kidney Disease in Patients Undergoing Fecal Microbiota Transplantation.

Chronic kidney disease (CKD) is a progressive loss of renal function in which gut dysbiosis is involved. Fecal microbiota transplantation (FMT) may be a promising alternative for restoring gut microbiota and treating CKD. This study evaluated the changes in CKD progression in patients treated with FMT. Patients with diabetes and/or hypertension with CKD clinical stages 2, 3, and 4 in this single-center, double-blind, randomized, placebo-controlled clinical trial (NCT04361097) were randomly assigned to receive either FMT or placebo capsules for 6 months. Laboratory and stool metagenomic analyses were performed. A total of 28 patients were included (15 FMT and 13 placebo). Regardless of CKD stages, patients responded similarly to FMT treatment. More patients (53.8%) from the placebo group progressed to CKD than the FMT group (13.3%). The FMT group maintained stable renal function parameters (serum creatinine and urea nitrogen) compared to the placebo group. Adverse events after FMT treatment were mild or moderate gastrointestinal symptoms. The abundance of Firmicutes and Actinobacteria decreased whereas Bacteroidetes, Proteobacteria and Roseburia spp. increased in the FMT group. CKD patients showed less disease progression after FMT administration. The administration of oral FMT in patients with CKD is a safe strategy, does not represent a risk, and has potential benefits.

Advances in fecal microbiota transplantation for the treatment of diabetes mellitus.

Diabetes mellitus (DM) refers to a group of chronic diseases with global prevalence, characterized by persistent hyperglycemia resulting from various etiologies. DM can harm various organ systems and lead to acute or chronic complications, which severely endanger human well-being. Traditional treatment mainly involves controlling blood sugar levels through replacement therapy with drugs and insulin; however, some patients still find a satisfactory curative effect difficult to achieve. Extensive research has demonstrated a close correlation between enteric dysbacteriosis and the pathogenesis of various types of DM, paving the way for novel therapeutic approaches targeting the gut microbiota to manage DM. Fecal microbiota transplantation (FMT), a method for re-establishing the intestinal microbiome balance, offers new possibilities for treating diabetes. This article provides a comprehensive review of the correlation between DM and the gut microbiota, as well as the current advancements in FMT treatment for DM, using FMT as an illustrative example. This study aims to offer novel perspectives and establish a theoretical foundation for the clinical diagnosis and management of DM.

Microbiota Transplantation as an Adjunct to Standard Periodontal Treatment in Periodontal Disease: A Systematic Review.

Periodontitis is a disease linked to severe dysbiosis of the subgingival microbiome. The treatment of periodontitis aims to change the dysbiosis environment to a symbiosis environment. We hypothesized that oral microbiota transplantation can lead to a significant improvement in periodontitis. Therefore, the aim of this study was to determine the effectiveness of microbiota transplantation after standard periodontal treatment in periodontitis patients. The search strategy was carried out by using the Boolean term "AND" to combine the keywords, which were "periodontitis AND microbiota transplantation". Due to the limited resources of the study, we included both in vitro and in vivo investigations in this systematic review. The QUIN risk of bias tool was employed to assess the risk of bias in in vitro studies, while SYRCLE's risk of bias assessment was used for in vivo studies. Oral microbiota transplants (OMTs) have shown potential in treating periodontitis. OMTs significantly reduced periodontitis-associated pathogenic microbial species (P. endodontalis, Prevotella intermedia, T. vincentii, Porphyromonas sp.) and increased beneficial bacteria (P. melaninogenica, Fusobacterium nucleatum, P. catoniae, Capnocytophaga ochracea, C. sputigena, C. gingivalis, Haemophilus parainfluenzae, and Neisseria elongata) upon in vitro testing. Furthermore, in the in vivo tests, single adjunctive OMT also had an effect on the oral microbiota composition compared to the full-mouth mechanical and antimicrobial debridement. OMTs may be cheaper and more effective at addressing high-risk individuals. At present, it is not possible to provide OMT clinical advice due to the lack of available information. This treatment needs to be subjected to more safety and efficacy testing before being included human clinical trials.

Safety profile and effects on the peripheral immune response of fecal microbiota transplantation in clinically healthy dogs.

BACKGROUND: Fecal microbiota transplantation (FMT) is increasingly used for gastrointestinal and extra-gastrointestinal diseases in veterinary medicine. However, its effects on immune responses and possible adverse events have not been systematically investigated. HYPOTHESIS/OBJECTIVES: Determine the short-term safety profile and changes in the peripheral immune system after a single FMT administration in healthy dogs. ANIMALS: Ten client-owned, clinically healthy dogs as FMT recipients, and 2 client-owned clinically healthy dogs as FMT donors. METHODS: Prospective non-randomized clinical trial. A single rectal enema of 5 g/kg was given to clinically healthy canine recipients. During the 28 days after FMT administration, owners self-reported adverse events and fecal scores. On Days 0 (baseline), 1, 4, 10, and 28 after FMT, fecal and blood samples were collected. The canine fecal dysbiosis index (DI) was calculated using qPCR. RESULTS: No significant changes were found in the following variables: CBC, serum biochemistry, C-reactive protein, serum cytokines (interleukins [IL]-2, -6, -8, tumor necrosis factor [TNF]-α), peripheral leukocytes (B cells, T cells, cluster of differentiation [CD]4+ T cells, CD8+ T cells, T regulatory cells), and the canine DI. Mild vomiting (n = 3), diarrhea (n = 4), decreased activity (n = 2), and inappetence (n = 1) were reported, and resolved without intervention. CONCLUSIONS AND CLINICAL IMPORTANCE: Fecal microbiota transplantation did not significantly alter the evaluated variables and recipients experienced minimal adverse events associated with FMT administration. Fecal microbiota transplantation was not associated with serious adverse events, changes in peripheral immunologic variables, or the canine DI in the short-term.

Rejuvenating fecal microbiota transplant enhances peripheral nerve repair in aged mice by modulating endoneurial inflammation.

Peripheral nerve injury (PNI) resulting from trauma or neuropathies can cause significant disability, and its prognosis deteriorates with age. Emerging evidence suggests that gut dysbiosis and reduced fecal short-chain fatty acids (SCFAs) contribute to an age-related systemic hyperinflammation (inflammaging), which hinders nerve recovery after injury. This study thus aimed to evaluate the pro-regenerative effects of a rejuvenating fecal microbiota transplant (FMT) in a preclinical PNI model using aged mice. Aged C57BL/6 mice underwent bilateral crush injuries to their sciatic nerves. Subsequently, they either received FMT from young donors at three and four days after the injury or retained their aged gut microbiota. We analyzed gut microbiome composition and SCFA concentrations in fecal samples. The integrity of the ileac mucosal barrier was assessed by immunofluorescence staining of Claudin-1. Flow cytometry was utilized to examine immune cells and cytokine production in the ileum, spleen, and sciatic nerve. Various assessments, including behavioural tests, electrophysiological studies, and morphometrical analyses, were conducted to evaluate peripheral nerve function and repair following injury. Rejuvenating FMT reversed age-related gut dysbiosis by increasing Actinobacteria, especially Bifidobacteriales genera. This intervention also led to an elevation of gut SCFA levels and mitigated age-related ileac mucosal leakiness in aged recipients. Additionally, it augmented the number of T-helper 2 (Th2) and regulatory T (Treg) cells in the ileum and spleen, with the majority being positive for anti-inflammatory interleukin-10 (IL-10). In sciatic nerves, rejuvenating FMT resulted in increased M2 macrophage counts and a higher IL-10 production by IL-10+TNF-α- M2 macrophage subsets. Ultimately, restoring a youthful gut microbiome in aged mice led to improved nerve repair and enhanced functional recovery after PNI. Considering that FMT is already a clinically available technique, exploring novel translational strategies targeting the gut microbiome to enhance nerve repair in the elderly seems promising and warrants further evaluation.

Dysbiosis in Multiple Sclerosis: Can Immunoglobulin Y Supplements Help?

The role of gut microbiota in autoimmune disorders like multiple sclerosis is gaining attention. Multiple sclerosis is characterized by inflammation, demyelination, and neurodegeneration in the central nervous system. Alterations in gut microbiota have been linked to multiple sclerosis development, with decreased beneficial bacteria and increased harmful species. The gut-brain axis is a complex interface influencing bidirectional interactions between the gut and the brain. Dysbiosis, an imbalance in gut microbiota, has been associated with autoimmune diseases. The influence of gut microbiota in multiple sclerosis is reversible, making it a potential therapeutic target. Probiotics, prebiotics, and fecal microbiota transplantation have shown promise in multiple sclerosis treatment, with positive effects on inflammation and immune regulation. Immunoglobulin Y (IgY) supplements derived from chicken egg yolk have potential as nutraceuticals or dietary supplements. IgY technology has been effective against various infections, and studies have highlighted its role in modulating gut microbiota and immune responses. Clinical trials using IgY supplements in multiple sclerosis are limited but have shown positive outcomes, including reduced symptoms, and altered immune responses. Future research directions involve understanding the mechanisms of IgY's interaction with gut microbiota, optimal dosage determination, and long-term safety assessments. Combining IgY therapy with other interventions and investigating correlations between microbiota changes and clinical outcomes are potential avenues for advancing multiple sclerosis treatment with IgY supplements.

Fecal microbiota transplantation stimulates type 2 and tolerogenic immune responses in a mouse model.

OBJECTIVES: Clostridioides difficile infection (CDI) is the leading hospital-acquired infection in North America. While previous work on fecal microbiota transplantation (FMT), a highly effective treatment for CDI, has focused on colonization resistance mounted against C. difficile by FMT-delivered commensals, the effects of FMT on host gene expression are relatively unexplored. This study aims to identify transcriptional changes associated with FMT, particularly changes associated with protective immune responses. METHODS: Gene expression was assessed on day 2 and day 7 after FMT in mice after antibiotic-induced dysbiosis. Flow cytometry was also performed on colon and mesenteric lymph nodes at day 7 to investigate changes in immune cell populations. RESULTS: FMT administration after antibiotic-induced dysbiosis successfully restored microbial alpha diversity to levels of donor mice by day 7 post-FMT. Bulk RNA sequencing of cecal tissue at day 2 identified immune genes, including both pro-inflammatory and Type 2 immune pathways as upregulated after FMT. RNA sequencing was repeated on day 7 post-FMT, and expression of these immune genes was decreased along with upregulation of genes associated with restoration of intestinal homeostasis. Immunoprofiling on day 7 identified increased colonic CD45+ immune cells that exhibited dampened Type 1 and heightened regulatory and Type 2 responses. These include an increased abundance of eosinophils, alternatively activated macrophages, Th2, and T regulatory cell populations. CONCLUSION: These results highlight the impact of FMT on host gene expression, providing evidence that FMT restores intestinal homeostasis after antibiotic treatment and facilitates tolerogenic and Type 2 immune responses.

Gut dysbiosis is linked to metabolic syndrome in obese Egyptian women: potential treatment by probiotics and high fiber diets regimen.

Metabolic syndrome (MetS) is defined as a cluster of glucose intolerance, hypertension, dyslipidemia, and central obesity with insulin resistance. The role of gut microbiota in metabolic disorders is increasingly considered. To investigate the effects of probiotic supplements and hypocaloric high fiber regimen on MetS in obese Egyptian women. A longitudinal follow-up intervention study included 58 obese Egyptian women, with a mean age of 41.62 ± 10.70 years. They were grouped according to the criteria of MetS into 2 groups; 23 obese women with MetS and 35 ones without MetS. They followed a hypocaloric high fiber regimen weight loss program, light physical exercise, and received a probiotic supplement daily for 3 months. For each participating woman, blood pressure, anthropometric measurements, basal metabolic rate (BMR), dietary recalls, laboratory investigations, and microbiota analysis were acquired before and after 3 months of follow-up. After intervention by the probiotic and hypocaloric high fiber regimen and light exercise, reduction ranged from numerical to significant difference in the anthropometric parameters, blood pressure, and BMR was reported. All the biochemical parameters characterized by MetS decreased significantly at p ≤ 0.05-0.01. Before the intervention, results revealed abundant of Bacteroidetes bacteria over Firmicutes with a low Firmicutes/Bacteroidetes ratio. After the intervention, Log Lactobacillus, Log Bifidobacteria, and Log Bacteroidetes increased significantly in both groups, while Log Firmicutes and the Firmicutes/Bacteroidetes Ratio revealed a significant decrease. In conclusion, this study's results highlight a positive trend of probiotics supplementation with hypocaloric high-fiber diets in amelioration of the criteria of the Mets in obese Egyptian women.

Just a gut feeling: Faecal microbiota transplant for treatment of depression - A mini-review.

BACKGROUND: The microbiota-gut-brain axis (MGBA) allows bidirectional crosstalk between the brain and gut microbiota (GM) and is believed to contribute to regulating mood/cognition/behaviour/metabolism/health and homeostasis. Manipulation of GM through faecal microbiota transplant (FMT) is a new, exciting and promising treatment for major depressive disorder (MDD). AIMS: This mini-review examines current research into GM and FMT as a therapy for depression. METHODS: Original research articles published in Medline/Cochrane Library/PubMed/EMBASE/PsycINFO databases/National Institute of Health website Clinicaltrials.gov/controlled-trials.com were searched. Full articles included in reference lists were evaluated. We summarise current data on GM and depression and discuss communication through the MGBA and the interaction of antidepressants and GM through this. We review compositions of dysbiosis in depressed cohorts, focusing on future directions in the treatment of MDD. RESULTS: Studies have demonstrated significant gut dysbiosis in depressed patients compared to healthy cohorts, with overgrowth of pro-inflammatory microbiota, reduction in anti-inflammatory species and reduced overall stability and taxonomic richness. FMT allows the introduction of healthy microbiota into the gastrointestinal tract, facilitating the restoration of eubiosis. CONCLUSION: The GM plays an integral role in human health and disease through its communication with the rest of the body via the MGBA. FMT may provide a means to transfer the healthy phenotype into the recipient and this concept in humans is attracting enormous attention as a prospective treatment for psychopathologies, such as MDD, in the future. It may be possible to manipulate the GM in a number of ways, but further research is needed to determine the exact likelihood and profiles involved in the development and amelioration of MDD in humans, as well as the long-term effects and potential risks of this procedure.

Exploring the role of oral microbiome dysbiosis in cardiometabolic syndrome and smoking.

Oral microbiome research has gained significant interest in recent years due to its potential impact on overall health. Smoking has been identified as a significant modulator of the oral microbiome composition, leading to dysbiosis and possible health consequences. Research has primarily focused on the association between smoking and oral microbiome, as well as smoking's association with cardiometabolic syndrome (CMS). This narrative review presents an overview of the recent findings and current knowledge on the oral microbiome and its role in CMS, including the effects of smoking and ethnicity. We discussed the development and composition of the oral microbiome and the association of periodontitis with diabetes and cardiovascular diseases. Furthermore, we highlighted the correlations between oral microbiome and CMS factors, such as diabetes, hypertension, dyslipidemia, and obesity. There is a need for further research in this area to better understand the mechanisms underlying the impact of smoking on oral microbiome dysbiosis and the development of CMS. Interestingly, geographic location and ethnicity have been shown to impact the oral microbiome profiles across populations. This knowledge will help develop personalized disease prevention and treatment approaches considering individual differences in oral microbiome composition. Understanding the complex interplay between oral microbiome, smoking, and CMS is essential for developing effective prevention and treatment strategies for a wide range of diseases.

The effect of microbiome therapy on COVID-19-induced gut dysbiosis: A narrative and systematic review.

AIMS: Emerging evidence highlights the role of COVID-19 in instigating gut dysbiosis, with repercussions on disease severity and bidirectional gut-organ communication involving the lung, heart, brain, and liver. This study aims to evaluate the efficacy of probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) in addressing gut dysbiosis associated with COVID-19, as well as their impact on related disease severity and clinical outcomes. MATERIALS AND METHODS: We systematically review 27 studies exploring the efficacy of different microbiome-modulating therapies: probiotics, prebiotics, synbiotics, and fecal microbiota transplantation as potential interventions for COVID-19. KEY FINDINGS: The probiotics and synbiotics investigated encompassed a spectrum of eight bacterial and fungal genera, namely Lactobacillus, Bifidobacterium, Streptococcus, Enterococcus, Pediococcus, Bacillus, Saccharomyces, and Kluyveromyces. Noteworthy prebiotics employed in these studies included chestnut tannin, galactooligosaccharides, fructooligosaccharides, xylooligosaccharide, and resistant dextrin. The majority of the investigated biotics exhibited positive effects on COVID-19 patients, manifesting in symptom alleviation, inflammation reduction, and notable decreases in mortality rates. Five studies reported death rates, showing an average mortality ranging from 0 % to 11 % in the intervention groups, as compared to 3 % to 30 % in the control groups. Specifically, probiotics, prebiotics, and synbiotics demonstrated efficacy in diminishing the duration and severity of symptoms while significantly accelerating viral and symptomatic remission. FMT emerged as a particularly effective strategy, successfully restoring gut microbiota and ameliorating gastrointestinal disorders. SIGNIFICANCE: The insights gleaned from this review significantly contribute to our broader comprehension of the therapeutic potential of biotics in addressing COVID-19-related gut dysbiosis and mitigating secondary multi-organ complications.

Fecal microbiota transplantation ameliorates abdominal obesity through inhibiting microbiota-mediated intestinal barrier damage and inflammation in mice.

Abdominal obesity (AO), characterized by the excessive abdominal fat accumulation, has emerged as a significant public health concern due to its metabolic complications and escalating prevalence worldwide, posing a more pronounced threat to human health than general obesity. While certain studies have indicated that intestinal flora contributed to diet-induced general obesity, the precise involvement of gut microbiota in the development of AO, specifically the accumulation of abdominal fat, remains inadequately explored. In this study, the 16 S rDNA sequencing was employed to analyze gut flora alterations, and the intestinal microbiota dysbiosis characterized by a vanishing decline of Akkermansia was found in the AO group. Along with notable gut microbiota changes, the intestinal mucosal barrier damage and metabolic inflammation were detected, which collectively promoted metabolic dysregulation in AO. Furthermore, the metabolic inflammation and AO were ameliorated after the intestinal microbiota depletion with antibiotics (ABX) drinking, underscoring a significant involvement of gut microbiota dysbiosis in the progression of AO. More importantly, our findings demonstrated that the transplantation of healthy intestinal flora successfully reversed the gut microbiota dysbiosis, particularly the decline of Akkermansia in the AO group. The gut flora reshaping has led to the repair of gut barrier damage and mitigation of metabolic inflammation, which ultimately ameliorated abdominal fat deposition. Our study established the role of interactions between gut flora, mucus barrier, and metabolic inflammation in the development of AO, thereby offering a theoretical foundation for the clinical application of fecal microbiota transplantation (FMT) as a treatment for AO.

Current perspectives on fecal microbiota transplantation in inflammatory bowel disease.

Fecal microbiota transplantation (FMT) has emerged as a promising therapeutic modality within the domain of inflammatory bowel disease (IBD). While FMT has secured approval and demonstrated efficacy in addressing recurrent and refractory Clostridioides difficile infection, its application in IBD remains an area of active exploration and research. The current status of FMT in IBD reflects a nuanced landscape, with ongoing investigations delving into its effectiveness, safety and optimal implementation. Early-stage clinical trials and observational studies have provided insights into the potential of FMT to modulate the dysbiotic gut microbiota associated with IBD, aiming to mitigate inflammation and promote mucosal healing. However, considerable complexities persist, including variations in donor selection, treatment protocols and outcome assessments. Challenges in standardizing FMT protocols for IBD treatment are compounded by the dynamic nature of the gut microbiome and the heterogeneity of IBD itself. Despite these challenges, enthusiasm for FMT in IBD emanates from its capacity to address gut microbial dysbiosis, signifying a paradigm shift towards more comprehensive approaches in IBD management. As ongoing research progresses, an enhanced understanding of FMT's role in IBD therapy is anticipated. This article synthesizes the current status of FMT in IBD, elucidating the attendant challenges and aspiring towards the refinement of its application for improved patient outcomes.

Dysbiosis of gut microbiota and metabolites is associated with radiation-induced colorectal fibrosis and is restored by adipose-derived mesenchymal stem cell therapy.

AIMS: This study aimed to investigate the effects of adipose-derived mesenchymal stem cells (ADSCs) on radiation-induced colorectal fibrosis (RICF) along with the associated dysbiosis of gut microbiota and metabolites. MAIN METHODS: Fecal microbiota were assessed through 16S rRNA gene sequencing, and the fecal metabolome was characterized using liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry. The correlation between microbiota and metabolome data was explored. KEY FINDINGS: ADSC injection demonstrated a significant restoration of radiation-induced intestinal damage in vivo. At the phylum level, irradiated rats exhibited an increase in Bacteroidota and Campilobacterota, and a decrease in Firmicutes and Desulfobacterota, contrasting with the ADSC treatment group. Metabolomic analysis revealed 72 differently expressed metabolites (DEMs) from gas chromatography-mass spectrometry and 284 DEMs from liquid chromatography-mass spectrometry in the radiation group compared to the blank group. In the ADSC treatment group versus the radiation group, 36 DEMs from gas chromatography-mass spectrometry and 341 DEMs from liquid chromatography-mass spectrometry were identified. KEGG enrichment analysis implicated pathways such as steroid hormone biosynthesis, gap junction, primary bile acid biosynthesis, citrate cycle, cAMP signaling pathway, and alanine, aspartate, and glutamate metabolism during RICF progression and after treated with ADSCs. Correlation analysis highlighted the role of ADSCs in modulating the metabolic process of Camelledionol in fecal Bacteroides. SIGNIFICANCE: These findings underscore the potential of ADSCs in reversing dysbiosis and restoring normal colonic flora in the context of RICF, offering valuable insights for therapeutic interventions targeting radiation-induced complications.

A comprehensive guide to assess gut mycobiome and its role in pathogenesis and treatment of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is an immune mediated chronic inflammatory disorder of gastrointestinal tract, which has underlying multifactorial pathogenic determinants such as environmental factors, susceptibility genes, gut microbial dysbiosis and a dysregulated immune response. Human gut is a frequent inhabitant of complex microbial ecosystem encompassing bacteria, viruses, parasites, fungi and other microorganisms that have an undisputable role in maintaining balanced homeostasis. All of these microbes interact with immune system and affect human gut physiology either directly or indirectly with interaction of each other. Intestinal fungi represent a smaller but crucial component of the human gut microbiome. Besides interaction with bacteriome and virome, it helps in balancing homoeostasis between pathophysiological and physiological processes, which is often dysregulated in patients with IBD. Understanding of gut mycobiome and its clinical implications are still in in its infancy as opposed to bacterial component of gut microbiome, which is more often focused. Modulation of gut mycobiome represents a novel and promising strategy in the management of patients with IBD. Emerging mycobiome-based therapies such as diet interventions, fecal microbiota transplantation (FMT), probiotics (both fungal and bacterial strains) and antifungals exhibit substantial effects in calibrating the gut mycobiome and restoring dysbalanced immune homeostasis by restoring the core gut mycobiome. In this review, we summarized compositional and functional diversity of the gut mycobiome in healthy individuals and patients with IBD, gut mycobiome dysbiosis in patients with IBD, host immune-fungal interactions and therapeutic role of modulation of intestinal fungi in patients with IBD.

Intestinal macrophages in pathogenesis and treatment of gut leakage: current strategies and future perspectives.

Macrophages play key roles in tissue homeostasis, defense, disease, and repair. Macrophages are highly plastic and exhibit distinct functional phenotypes based on micro-environmental stimuli. In spite of several advancements in understanding macrophage biology and their different functional phenotypes in various physiological and pathological conditions, currently available treatment strategies targeting macrophages are limited. Macrophages' high plasticity and diverse functional roles-including tissue injury and wound healing mechanisms-mark them as potential targets to mine for efficient therapeutics to treat diseases. Despite mounting evidence on association of gut leakage with several extraintestinal diseases, there is no targeted standard therapy to treat gut leakage. Therefore, there is an urgent need to develop therapeutic strategies to treat this condition. Macrophages are the cells that play the largest role in interacting with the gut microbiota in the intestinal compartment and exert their intended functions in injury and repair mechanisms. In this review, we have summarized the current knowledge on the origins and phenotypes of macrophages. The specific role of macrophages in intestinal barrier function, their role in tissue repair mechanisms, and their association with gut microbiota are discussed. In addition, currently available therapies and the putative tissue repair mediators of macrophages for treating microbiota dysbiosis induced gut leakage are also discussed. The overall aim of this review is to convey the intense need to screen for microbiota induced macrophage-released prorepair mediators, which could lead to the identification of potential candidates that could be developed for treating the leaky gut and associated diseases.

Can the Evidence-Based Use of Probiotics (Notably Saccharomyces boulardii CNCM I-745 and Lactobacillus rhamnosus GG) Mitigate the Clinical Effects of Antibiotic-Associated Dysbiosis?

Dysbiosis corresponds to the disruption of a formerly stable, functionally complete microbiota. In the gut, this imbalance can lead to adverse health outcomes in both the short and long terms, with a potential increase in the lifetime risks of various noncommunicable diseases and disorders such as atopy (like asthma), inflammatory bowel disease, neurological disorders, and even behavioural and psychological disorders. Although antibiotics are highly effective in reducing morbidity and mortality in infectious diseases, antibiotic-associated diarrhoea is a common, non-negligible clinical sign of gut dysbiosis (and the only visible one). Re-establishment of a normal (functional) gut microbiota is promoted by completion of the clinically indicated course of antibiotics, the removal of any other perturbing external factors, the passage of time (i.e. recovery through the microbiota's natural resilience), appropriate nutritional support, and-in selected cases-the addition of probiotics. Systematic reviews and meta-analyses of clinical trials have confirmed the strain-specific efficacy of some probiotics (notably the yeast Saccharomyces boulardii CNCM I-745 and the bacterium Lactobacillus rhamnosus GG) in the treatment and/or prevention of antibiotic-associated diarrhoea in children and in adults. Unusually for a probiotic, S. boulardii is a eukaryote and is not therefore directly affected by antibiotics-making it suitable for administration in cases of antibiotic-associated diarrhoea. A robust body of evidence from clinical trials and meta-analyses shows that the timely administration of an adequately dosed probiotic (upon initiation of antibiotic treatment or within 48 h) can help to prevent or resolve the consequences of antibiotic-associated dysbiosis (such as diarrhoea) and promote the resilience of the gut microbiota and a return to the pre-antibiotic state. A focus on the prescription of evidence-based, adequately dosed probiotics should help to limit unjustified and potentially ineffective self-medication.