Microbiota transplant therapy is an emerging therapy for inflammatory bowel disease, but factors influencing its efficacy and mechanism remain poorly understood. In this narrative review, we outline key elements affecting therapeutic outcomes, including donor factors (such as age and patient relationship), recipient factors, control selection, and elements impacting engraftment and its correlation with clinical response. We also examine potential mechanisms through inflammatory bowel disease trials, focusing on the interplay between the microbiota, host, and immune system. Finally, we briefly explore potential future directions for microbiota transplant therapy and promising emerging treatments.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract influenced by genetic, environmental, immune, and microbial factors. Reduced gut microbial diversity and elevated proinflammatory bacteria levels in IBD disrupt mucosal immunity, barrier function, and inflammatory pathways. Fecal microbiota transplantation (FMT) is a potential therapy to restore microbial balance. Studies suggest that FMT may induce remission in mild-to-moderate ulcerative colitis but show limited efficacy in Crohn's disease and pouchitis. Donor microbiota colonization correlates with remission, but varied study designs challenge findings. Further research is required to standardize FMT protocols, optimize donor selection, and ensure long-term safety.

Regulatory T cells (Tregs) are a specialized subset of suppressive T cells that are essential for maintaining self-tolerance, regulating effector T cells, managing microbial infections, preventing tumors, allergies, and autoimmune disorders, and facilitating allograft transplantation. Disruptions in Treg function or abundance contribute to an imbalance between pathogenic and protective immune cells in autoimmune diseases. Recently, one promising treatment strategy to restore immune balance involves the selective expansion or manipulation of Tregs using low-dose IL-2 therapy, adoptive Treg cell transfer, and chimeric antigen receptor (CAR)-Treg approaches. Tregs have been shown in an increasing number of research studies to prevent or even treat a variety of disorders, such as tumors, autoimmune and allergic diseases, transplant rejection, and graft-versus-host disease. A thorough comprehension of Treg function is anticipated to provide clear prospects for effective Treg immunotherapy in the treatment of a wide range of diseases. This review provides an overview of Tregs biology, including their functions, suppressive mechanisms, phenotypic markers, as well as their involvement in disease settings. Furthermore, we discuss the therapeutic potential of different Treg subpopulations and their translational applications in the treatment of autoimmune diseases.

Crohn's disease (CD) is characterized by an inflammatory response to gut microbiota. Macrophages and dendritic cells play an active role in CD inflammation. Specific microbiota have been implicated in the pathogenesis of ileal CD. We investigated the phagocyte-associated microbiome using an unbiased sequencing approach to identify potential pathobionts and elucidate the host response to these microbes.

We collected ileal and colonic mucosal biopsies from CD patients and controls without inflammatory bowel disease (IBD), isolated lamina propria phagocytes (CD11b+ cells), and performed deep RNA sequencing (n = 37). Reads were mapped to the human genome for host gene expression analysis and a prokaryotic database for microbiome taxonomic and metatranscriptomic profiling. Results were confirmed in a second IBD cohort (n = 17). Lysed lamina propria cells were plated for bacterial culturing; isolated colonies underwent whole genome sequencing (n = 11).

Crohn's disease ileal phagocytes contained higher relative abundances of Escherichia coli, Ruminococcus gnavus, and Enterocloster spp. than those from controls. CD phagocyte-associated microbes had increased expression of lipopolysaccharide (LPS) biosynthesis pathways. Phagocytes with a higher pathobiont burden showed increased expression of pro-inflammatory and antimicrobial genes, including PI3 (antimicrobial peptide) and BPIFB1 (LPS-binding molecule). E. coli isolated from the CD lamina propria had more flagellar motility and antibiotic resistance genes than control-derived strains.

Lamina propria resident phagocytes harbor bacterial strains that may act as pathobionts in CD. Our findings shed light on the role of pathobionts and the immune response in CD pathogenesis and suggest new targets for therapies.

Inflammatory bowel disease (IBD), comprising ulcerative colitis and Crohn's disease, is a chronic inflammatory condition with global prevalence and varying incidence. The IBD pathogenesis involves intricate interactions among genetic, host and environmental factors, leading to dysregulated immune responses and chronic intestinal inflammation. Alongside elevated levels of inflammatory cytokines and altered miRNAs expression, more studies highlight significant dysbiosis in both fecal and ileal microbiota of IBD patients. This dysbiosis is characterized by an increase in pro-inflammatory and mucin-degrading bacteria (e.g., Fusobacterium spp., Escherichia spp.) and a decline in short-chain fatty acids (SCFAs) -producing microbes (e.g., Roseburia spp., Faecalibacterium spp.) which play a protective role in gut health. Diet emerges as a key environmental factor influencing IBD onset and progression and recent advancements in"omics" technologies, such as genomics, transcriptomics, and metabolomics, provide a deeper understanding of the molecular interactions between genes, gut microbiota (GM) and nutrition. Finally, new technologies like artificial intelligence (AI), further enhance findings by enabling data integration and personalized dietary strategies. In this scenario, this review aims to summarize accumulating data on the effects of dietary interventions in IBD patients and introduce the role of artificial intelligence (AI) in facilitating precision dietary approaches to improve IBD management.

The enteric microbiota drives inflammation in Crohn's disease. Yet, there are no placebo controlled trials evaluating the efficacy and safety of faecal microbiota transplantation (FMT) in inducing and maintaining remission in patients with active Crohn's disease. The Microbial Restoration (MIRO) study aims to establish this evidence.

At two specialist inflammatory bowel disease centres, 120 enrolled patients will have a 3-week period of diet optimisation (removal of ultra-processed foods) together with a 7-day course of antibiotics (to facilitate subsequent FMT engraftment). Patients will then be stratified to upper gut (for disease proximal to the splenic flexure) or lower gut (distal to the splenic flexure) disease. Patients will then be randomised in a 2:1 ratio to receive anaerobically prepared stool or placebo for 8 weeks either by gastroscopy, or colonoscopy and enemas. Clinical response at 8 weeks (Crohn's Disease Activity Index (CDAI) reduction ≥100 points or to <150 points) is the primary outcome measure. Non-responders to placebo and partial responders to FMT (CDAI decrease <100 but >70) receive FMT for weeks 8-16.Patients achieving clinical response from FMT after 8 or 16 weeks will be randomised in a 1:1 ratio to either a 44-week maintenance phase of FMT or placebo. Patients will receive FMT from one donor throughout the study.The MIRO study will establish whether FMT is an effective and safe therapy to induce and maintain remission in patients with active Crohn's disease.

Ethical approval has been received by the St Vincent's Hospital Melbourne Human Research Ethics Committee (HREC-A 084/21). The results will be disseminated in peer-reviewed journals and presented at international conferences.

ClinicalTrials.gov: NCT04970446; Registered on 20 July 2021.

This editorial comments on the article by Wu et al in the World Journal of Gastroenterology. The article explored the relationship between mesenteric adipose tissue, creeping fat, inflammation, and gut microbiota in Crohn's disease (CD). We discussed three key aspects of the interaction between gut microbiota and inflammatory bowel disease (IBD): The physiological functions of the gut microbiota, the potential role of probiotics in IBD treatment; and the effect of fecal microbiota transplantation (FMT) in combating IBD. IBD, comprising CD and ulcerative colitis (UC), is influenced by the gut microbiota. Changes in gut microbiota composition disrupt intestinal function and promote chronic inflammation, but the exact mechanisms remain unclear. Probiotics have demonstrated some efficacy in inducing remission in UC, though their effectiveness in CD is still debated. FMT shows promise in treating IBD, especially UC, by restoring gut microbiota diversity and inducing clinical remission. As for CD, FMT has potential, but more studies are needed to confirm its long-term effectiveness and safety. Dietary approaches may help manage IBD symptoms or disease activity, but patient adherence is crucial. Clinicians and researchers must recognize the importance of the gut microbiota and the need for personalized therapies targeting microbial imbalances.

This article provides an overview of the advancements in the application of fecal microbiota transplantation (FMT) in treating diseases related to intestinal dysbiosis. FMT involves the transfer of healthy donor fecal microbiota into the patient's body, aiming to restore the balance of intestinal microbiota and thereby treat a variety of intestinal diseases such as recurrent Clostridioides difficile infection (rCDI), inflammatory bowel disease (IBD), constipation, short bowel syndrome (SBS), and irritable bowel syndrome (IBS). While FMT has shown high efficacy in the treatment of rCDI, further research is needed for its application in other chronic conditions. This article elaborates on the application of FMT in intestinal diseases and the mechanisms of intestinal dysbiosis, as well as discusses key factors influencing the effectiveness of FMT, including donor selection, recipient characteristics, treatment protocols, and methods for assessing microbiota. Additionally, it emphasizes the key to successful FMT. Future research should focus on optimizing the FMT process to ensure long-term safety and explore the potential application of FMT in a broader range of medical conditions.

Crohn's disease (CD), also known as cicatrizing enteritis, is an inflammatory bowel disease that occurs in the distal ileum and right colon of unknown cause and is also called inflammatory bowel disease (IBD) with ulcerative colitis (UC). In recent years, intestinal biota have been confirmed to play a significant role in various gastrointestinal diseases. Studies have found that intestinal microbiota disorders are closely associated with the onset and progression of Crohn's disease. Bacteroidetes, the second largest microbiota in the intestine, are crucial for equilibrium in the microbiota and intestinal environment. Certain Bacteroides can induce the development of Crohn's disease and aggravate intestinal inflammation directly or through their metabolites. Conversely, certain Bacteroides can reduce intestinal inflammation and symptoms of Crohn's disease. This article reviews the effect of several intestinal Bacteroides in the onset and progression of Crohn's disease and their impact on its treatment.

Perturbations in the intestinal microbiome are strongly linked to the pathogenesis of inflammatory bowel disease (IBD). Bacteria, fungi and viruses all make up part of a complex multi-kingdom community colonizing the gastrointestinal tract, often referred to as the gut microbiome. They can exert various effects on the host that can contribute to an inflammatory state. Advances in screening, multiomics and experimental approaches have revealed insights into host-microbiota interactions in IBD and have identified numerous mechanisms through which the microbiota and its metabolites can exert a major influence on the gastrointestinal tract. Looking into the future, the microbiome and microbiota-associated processes will be likely to provide unparalleled opportunities for novel diagnostic, therapeutic and diet-inspired solutions for the management of IBD through harnessing rationally designed microbial communities, powerful bacterial and fungal metabolites, individually or in combination, to foster intestinal health. In this Review, we examine the current understanding of the cross-kingdom gut microbiome in IBD, focusing on bacterial and fungal components and metabolites. We examine therapeutic and diagnostic opportunities, the microbial metabolism, immunity, neuroimmunology and microbiome-inspired interventions to link mechanisms of disease and identify novel research and therapeutic opportunities for IBD.

Microbiome research has expanded significantly in the last two decades, yet translating findings into clinical applications remains challenging. This perspective discusses the persistent issue of correlational studies in microbiome research and proposes an iterative method leveraging in silico, in vitro, ex vivo, and in vivo studies toward successful preclinical and clinical trials. The evolution of research methodologies, including the shift from small cohort studies to large-scale, multi-cohort, and even "meta-cohort" analyses, has been facilitated by advancements in sequencing technologies, providing researchers with tools to examine multiple health phenotypes within a single study. The integration of multi-omics approaches-such as metagenomics, metatranscriptomics, metaproteomics, and metabolomics-provides a comprehensive understanding of host-microbe interactions and serves as a robust hypothesis generator for downstream in vitro and in vivo research. These hypotheses must then be rigorously tested, first with proof-of-concept experiments to clarify the causative effects of the microbiota, and then with the goal of deep mechanistic understanding. Only following these two phases can preclinical studies be conducted with the goal of translation into the clinic. We highlight the importance of combining traditional microbiological techniques with big-data approaches, underscoring the necessity of iterative experiments in diverse model systems to enhance the translational potential of microbiome research.

Clinical data on oral fecal microbiota transplantation (FMT), a promising therapy for Crohn's disease (CD), are limited. Herein, we determined the short-term safety and feasibility of FMT for pediatric patients with active CD.

In this open-label, parallel-group, single-center prospective trial, patients with active CD were treated with oral FMT capsules combined with partial enteral nutrition (PEN) (80%). The control group comprised pediatric patients with active CD treated with PEN (80%) and immunosuppressants. Thirty-three patients (11.6 ± 1.82 years)-17 in the capsule and 16 in the control groups-were analyzed. Data regarding the adverse events, clinical reactions, intestinal microbiome composition, and biomarker parameters were collected and compared post-treatment.

At week 10, the clinical and endoscopic remission rates did not differ between the two groups. By week 10, the mean fecal calprotectin level, C-reactive protein level, erythrocyte sedimentation rate, simple endoscopic score for CD, and pediatric CD activity index decreased significantly in the capsule group (all P < 0.05). The main adverse event was mild-to-moderate constipation. Core functional genera, Agathobacter, Akkermansia, Roseburia, Blautia, Subdoligranulum, and Faecalibacterium, were lacking pre-treatment. Post-treatment, the implantation rates of these core functional genera increased significantly, which positively correlated with the anti-inflammatory factor, interleukin (IL)-10, and negatively correlated with the pro-inflammatory factor, IL-6. The combination of these six functional genera distinguished healthy children from those with CD (area under the curve = 0.96).

Oral FMT capsules combined with PEN (80%) could be an effective therapy for children with active CD. The six core functional genera identified here may be candidate biomarkers for identifying children with CD.

ClinicalTrials.gov, retrospectively registered, ID# NCT05321758, NCT05321745, date of registration: 2022-04-04.

The gut microbiome and human body have co-evolved in a synergistic host-microbial relationship. The ideal composition of human gut microbiota is an elusive concept, but every individual has a unique gut microbiota profile with regional differences. Newer diagnostic techniques have helped identify different bacteria and their roles in health and disease. The gut microbiome composition is affected by various factors like age, diet, immune system, environmental factors, exercise, and drugs. The microbiome has varied roles in metabolism, immune response, immune tolerance and antimicrobial protection. Diet plays an important role in maintaining the gut microbial diversity. Loss of homoeostasis in the microbiome results in dysbiosis. Dysbiosis plays a role in many dermatological diseases like atopic dermatitis, psoriasis, acne, rosacea, hidradenitis suppurativa, connective tissue disorders and many other systemic conditions like obesity, diabetes, neurological disease and malignancy. Reconstitution of the gut microbiome ecology in the form of bacteriotherapy with the reintegration of certain strains of microbiota has a beneficial role in many of these disorders.

Probiotics supplementations have been regarded as an effective strategy for colitis treatment. However, the effect of Ligilactobacillus salivarius Li01 on benzo[a]pyrene (BaP)-induced colitis in Mongolian gerbils remains unclear. In this study, we leverage a BaP-induced model of colitis that exhibits significant remission following Ligilactobacillus salivarius Li01 intervention, to conduct an animal experiment that integrates histopathological assessment, inflammatory cytokines, 16S rRNA sequencing, targeted metabolomic profiling to investigate the relationship between Ligilactobacillus salivarius Li01, gut microbiota, and colitis.

We demonstrated that the improvements in colon histopathological assessment and inflammatory cytokines by Ligilactobacillus salivarius Li01 supplementation are accompanied by alterations in gut microbiota structure marked by increased abundance of strains with probiotic potential belonging to Bifidobacterium and Eubacterium_coprostanoligenes. Targeted metabolomic profiling analysis showed that Ligilactobacillus salivarius Li01 supplementation increases the concentration of acetic, propionic, butyric, and valeric acid. Correlation analysis showed that the alteration in the indicators associated with colitis is closely correlated to the changed microbial taxa and short-chain fatty acids (SCFAs).

These data highlighted that Ligilactobacillus salivarius Li01 supplementation ameliorated the BaP-induced colitis, probably via modulating the structure of gut microbiota and promoting the production of SCFAs. Our findings provide preliminary evidence for a possible therapeutic strategy for the treatment of colitis based on host-microbiome interactions.

The dysbiosis of the gut microbiota has been identified as a central factor in the pathogenesis of inflammatory bowel disease (IBD), a chronic condition characterized by frequent recurrence and various adverse effects of traditional therapies. While treatments targeting the gut microbiota show promise, their efficacy in IBD management still requires extensive evaluation. Our systematic review analyzes recent studies to elucidate the advancements and challenges in treating IBD using microbial-based therapies.

Through a comprehensive systematic review spanning key scientific databases-PubMed, Embase, Cochrane, Web of Science, Scopus, and Google Scholar-we scrutinized the impact of probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) on individuals with IBD. Our detailed analysis covered study and participant demographics, along with seven key outcome measures: disease activity index, inflammatory markers, serum cytokines, microbiome composition, adverse effects, and the rates of remission and relapse.

From 6,080 initial search hits, we included 71 studies that assessed various interventions compared to placebo or standard medical therapy. Although there was notable variation in clinical results while assessing different outcomes, overall, probiotics, prebiotics, and synbiotics enhanced the success rates in inducing remission among IBD patients. Furthermore, we noted significant reductions in levels of pro-inflammatory markers and cytokines. Additionally, the requirement for steroids, hospitalization, and poor outcomes in endoscopic and histological scores were significantly reduced in individuals undergoing FMT.

Our investigation highlights the potential of targeting gut microbiota dysbiosis with microbial-based therapies in patients with IBD. We recommend conducting larger, placebo-controlled randomized trials with extended follow-up periods to thoroughly assess these treatments' clinical efficacy and safety before widespread recommendations for clinical application.

This article comments on the letter by Lowell et al, which addresses the next generation of combination therapy for inflammatory bowel disease (IBD). As the understanding of the pathogenesis of IBD continues to improve, treatment strategies are evolving rapidly. The letter examines the current status and future directions of combination therapy for IBD, focusing on approaches that combine biologics with immunomodulators and the emerging dual-biologic therapy (DBT). The traditional combination of biologics and immunomodulators has demonstrated preliminary efficacy by enhancing the effects of biologics through immunomodulation. However, concerns regarding long-term safety warrant careful evaluation. Recent trials, including DUET-Crohn's disease and DUET-ulcerative colitis, have shown promising potential for the broader adoption of DBT. Nevertheless, comprehensive data on efficacy and safety, as well as the effective integration of supportive treatments, remain essential to establish new paradigms for the next generation of IBD care.

Fecal microbiota transplantation (FMT) is an experimental treatment for ulcerative colitis (UC). We aimed to study microbial families associated with FMT treatment success.

We analyzed stools from 24 UC patients treated with 4 FMTs weekly after randomization for pretreatment during 3 weeks with budesonide (n = 12) or placebo (n = 12). Stool samples were collected 9 times pre-, during, and post-FMT. Clinical and endoscopic response was assessed 14 weeks after initiation of the study using the full Mayo score. Early withdrawal due to worsening of UC symptoms was classified as non-response.

Nine patients (38%) reached remission at week 14, and 15 patients had a partial response or non-response at or before week 14. With a Dirichlet multinomial mixture model, we identified 5 distinct clusters based on the microbiota composition of 180 longitudinally collected patient samples and 27 donor samples. A Prevotellaceae-dominant cluster was associated with poor response to FMT treatment. Conversely, the families Ruminococcaceae and Lachnospiraceae were associated with a successful clinical response. These associations were already visible at the start of the treatment for a subgroup of patients and were retained in repeated measures analyses of family-specific abundance over time. Responders were also characterized by a significantly lower Simpson dominance compared to non-responders.

The success of FMT treatment of UC patients appears to be associated with specific gut microbiota families, such as control of Prevotellaceae. Monitoring the dynamics of these microbial families could potentially be used to inform treatment success early during FMT.

The study was registered in the Netherlands Trial Register, with reference number NL9858.

Microbiota transplant therapy (MTT) is an emerging treatment for ulcerative colitis (UC). One proposed mechanism for the benefit of MTT is through engraftment of donor microbiota; however, engraftment kinetics are unknown. We identified SourceTracker as an efficient method both to determine engraftment and for the kinetic study of engrafting donor taxa to aid in determining the mechanism of how this therapy may treat UC.

Ulcerative colitis patients received either encapsulated (drug name MTP-101C) or placebo capsules daily for 8 weeks followed by a 4-week washout period. Amplicon sequence data from donors and patients were analyzed using the Bayesian algorithm SourceTracker.

Twenty-seven patients were enrolled, 14 to placebo and 13 to MTT. Baseline Shannon and Chao1 indices negatively correlated with week 12 donor engraftment for patients treated with active drug capsules but not for placebo patients. SourceTracker engraftment positively correlated with the week 12 distance from donors measured using the Bray-Curtis similarity metric in treated patients but not with placebo. Engraftment at week 12 was significantly higher in the MTT group than in the placebo group. We identified engrafting taxa from donors in our patients and quantified the proportion of donor similarity or engraftment during weeks 1 through 8 (active treatment) and week 12, 4 weeks after the last dose.

SourceTracker can be used as a simple and reliable method to quantify donor microbial community engraftment and donor taxa contribution in patients with UC and other inflammatory conditions treated with MTT.

Inflammatory bowel disease (IBD) comprises chronic and relapsing disorders of the gastrointestinal tract, characterized by dysregulated immune responses to the gut microbiome. The gut microbiome and diet are key environmental factors that influence the onset and progression of IBD and can be leveraged for treatment. In this review, we summarize the current evidence on the role of the gut microbiome and diet in IBD pathogenesis, and the potential of microbiome-directed therapies and dietary interventions to improve IBD outcomes. We discuss available data and the advantages and drawbacks of the different approaches to manipulate the gut microbiome, such as fecal microbiota transplantation, next-generation and conventional probiotics, and postbiotics. We also review the use of diet as a therapeutic tool in IBD, including the effects in induction and maintenance, special diets, and exclusive enteral nutrition. Finally, we highlight the challenges and opportunities for the translation of diet and microbiome interventions into clinical practice, such as the need for personalization, manufacturing and regulatory hurdles, and the specificity to take into account for clinical trial design.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline and progressive neuronal damage. Recent research has highlighted the significant roles of the gut microbiota and microRNAs (miRNAs) in the pathogenesis of AD. This review explores the intricate interaction between gut microbiota and miRNAs, emphasizing their combined impact on Alzheimer's progression. First, we discuss the bidirectional communication within the gut-brain axis and how gut dysbiosis contributes to neuroinflammation and neurodegeneration in AD. Changes in gut microbiota composition in Alzheimer's patients have been linked to inflammation, which exacerbates disease progression. Next, we delve into the biology of miRNAs, focusing on their roles in gene regulation, neurodevelopment, and neurodegeneration. Dysregulated miRNAs are implicated in AD pathogenesis, influencing key processes like inflammation, tau pathology, and amyloid deposition. We then examine how the gut microbiota modulates miRNA expression, particularly in the brain, potentially altering neuroinflammatory responses and synaptic plasticity. The interplay between gut microbiota and miRNAs also affects blood-brain barrier integrity, further contributing to Alzheimer's pathology. Lastly, we explore therapeutic strategies targeting this gut microbiota-miRNA axis, including probiotics, prebiotics, and dietary interventions, aiming to modulate miRNA expression and improve AD outcomes. While promising, challenges remain in fully elucidating these interactions and translating them into effective therapies. This review highlights the importance of understanding the gut microbiota-miRNA relationship in AD, offering potential pathways for novel therapeutic approaches aimed at mitigating the disease's progression.

Inflammatory bowel disease, particularly Crohn's disease (CD), has been linked to modifications in mesenteric adipose tissue (MAT) and the phenomenon known as "creeping fat" (CrF). The presence of CrF is believed to serve as a predictor for early clinical recurrence following surgical intervention in patients with CD. Notably, the incorporation of the mesentery during ileocolic resection for CD has been correlated with a decrease in surgical recurrence, indicating the significant role of MAT in the pathogenesis of CD. While numerous studies have indicated that dysbiosis of the gut microbiota is a critical factor in the development of CD, the functional implications of translocated microbiota within the MAT of CD patients remain ambiguous. This manuscript commentary discusses a recent basic research conducted by Wu et al. In their study, intestinal bacteria from individuals were transplanted into CD model mice, revealing that fecal microbiota transplantation (FMT) from healthy donors alleviated CD symptoms, whereas FMT from CD patients exacerbated these symptoms. Importantly, FMT was found to affect intestinal permeability, barrier function, and the levels of proinflammatory factors and adipokines. Collectively, these findings suggest that targeting MAT and CrF may hold therapeutic potential for patients with CD. However, the study did not evaluate the composition of the intestinal microbiota of the donors or the subsequent alterations in the gut microbiota. Overall, the gut microbiota plays a crucial role in the histopathology of CD, and thus, targeting MAT and CrF may represent a promising avenue for treatment in this patient population.

Extensive research has investigated the etiology of Crohn's disease (CD), encompassing genetic predisposition, lifestyle factors, and environmental triggers. Recently, the gut microbiome, recognized as the human body's second-largest gene pool, has garnered significant attention for its crucial role in the pathogenesis of CD. This paper investigates the mechanisms underlying CD, focusing on the role of 'creeping fat' in disease progression and exploring emerging therapeutic strategies, including fecal microbiota transplantation, enteral nutrition, and therapeutic diets. Creeping fat has been identified as a unique pathological feature of CD and has recently been found to be associated with dysbiosis of the gut microbiome. We characterize this dysbiotic state by identifying key microbiome-bacteria, fungi, viruses, and archaea, and their contributions to CD pathogenesis. Additionally, this paper reviews contemporary therapies, emphasizing the potential of biological therapies like fecal microbiota transplantation and dietary interventions. By elucidating the complex interactions between host-microbiome dynamics and CD pathology, this article aims to advance our understanding of the disease and guide the development of more effective therapeutic strategies for managing CD.

Gut microbiome-targeted therapies (MTTs), including prebiotics, probiotics, synbiotics, and fecal microbiota transplantation (FMT), have been widely used in inflammatory bowel diseases (IBD), but the best MTTs has not yet been confirmed. We performed a network meta-analysis (NMA) to examine this in ulcerative colitis (UC) and Crohn's disease (CD).

We searched for randomized controlled trials (RCTs) on the efficacy and safety of MTTs as adjuvant therapies for IBD until December 10, 2023. Data were pooled using a random effects model, with efficacy reported as pooled relative risks with 95% CIs, and interventions ranked according to means of surfaces under cumulative ranking values.

Thirty-eight RCTs met the inclusion criteria. Firstly, we compared the efficacy of MTTs in IBD patients. Only FMT and probiotics were superior to placebo in all outcomes, but FMT ranked best in improving clinical response rate and clinical and endoscopic remission rate, and probiotics ranked second in reducing clinical relapse rate showed significant efficacy, while prebiotics ranked first showed nonsignificant efficacy. Subsequently, we conducted NMA for specific MTT formulations in UC and CD separately, which revealed that FMT, especially combined FMT via colonoscopy and enema, showed significant efficacy and was superior in improving clinical response and remission rate of active UC patients. As for endoscopic remission and clinical relapse, multistrain probiotics based on specific genera of Lactobacillus and Bifidobacterium showed significant efficacy and ranked best in UC. In CD, we found that no MTTs were significantly better than placebo, but synbiotics comprising Bifidobacterium and fructo-oligosaccharide/inulin mix and Saccharomyces ranked best in improving clinical remission and reducing clinical relapse, respectively. Moreover, FMT was safe in both UC and CD.

FMT and multistrain probiotics showed superior efficacy in UC. However, the efficacy of MTTs varies among different IBD subtypes and disease stages; thus, the personalized treatment strategies of MTTs are necessary.

In this letter, we commented on the article by Wu et al. We examined the interactions between mesenteric adipose tissue, creeping fat, and gut microbiota in Crohn's disease (CD), a condition marked by chronic gastrointestinal inflammation with a rising global incidence. The pathogenesis of CD involves complex genetic, environmental, and microbial factors. Dysbiosis, which is an imbalance in gut microbial communities, is frequently observed in CD patients, highlighting the pivotal role of the gut microbiota in disease progression and the inflammatory response. Recent studies have shown that mesenteric adipose tissue and creeping fat actively contribute to inflammation by producing proinflammatory cytokines. The relationship between creeping fat and altered microbiota can shift from a potentially protective role to one that encourages bacterial translocation, further complicating disease management. Recent research has suggested that fecal microbiota transplantation could help restore microbial balance, offering a promising therapeutic strategy to improve clinical disease response.

Hemodialysis patients with end-stage renal disease (ESRD) are susceptible to infections and dysbiosis. Catheter-related infections are typically caused by opportunistic skin pathogens. This study aims to compare the skin microbiota changes around the exit site of tunneled cuffed catheters (peri-catheter group) and the contralateral site (control group).

ESRD patients on hemodialysis were recruited. The skin microbiota were collected with moist skin swabs and analyzed using high-throughput sequencing of the 16S rDNA V3-V4 region. After denoising, de-replication, and removal of chimeras, the reads were assigned to zero-radius operational taxonomic units (ZOTU).

We found significantly reduced alpha diversity in the peri-catheter group compared to the control group, as indicated by the Shannon, Jost, and equitability indexes, but not by the Chao1 or richness indexes. Beta diversity analysis revealed significant deviation of the peri-catheter microbiota from its corresponding control group. There was an overrepresentation of Firmicutes and an underrepresentation of Actinobacteria, Proteobacteria, and Acidobacteria at the phylum level in the peri-catheter group. The most abundant ZOTU (Staphylococcus spp.) drastically increased, while Cutibacterium, a commensal bacterium, decreased in the peri-catheter group. Network analysis revealed that the skin microbiota demonstrated covariance with both local and biochemical factors.

In conclusion, there was significant skin microbiota dysbiosis at the exit sites compared to the control sites in ESRD dialysis patients. Managing skin dysbiosis represents a promising target in the prevention of catheter-related bacterial infections.

Neuromyelitis optica spectrum disorder (NMOSD) is a central nervous system inflammatory demyelinating immune-mediated ailment, which is influenced by genetic, epigenetic, and environmental elements. The escalating incidence of NMOSD in recent years implies alterations in environmental risk factors. Recent research has established a correlation between gut microbiomes and the development of NMOSD.

Metagenomic shotgun sequencing and gas chromatography-mass spectrometry (GC-MS) were employed to assess alterations of the structure and function in the fecal microbiome, as well as levels of short-chain fatty acids (SCFAs) in fecal and blood samples, among individuals with neuromyelitis optica spectrum disorder (NMOSD) during the acute phase (n = 25), the remission phase (n = 11), and a group of healthy controls (HCs) (n = 24). We further explored the correlation between gut microbiota and the pathogenesis of NMOSD through fecal microbiota transplantation (FMT). The gut microbiome from human donors diagnosed with NMOSD or HCs was transplanted into germ-free mice, followed by an analysis of the alterations in the structure and functionality of the transplanted mice's gut microbiome. Additionally, the impact of microbiome transfer on the immunity and spinal cord of germ-free mice was assessed through various techniques, including ELISA, flow cytometry, western blot, histopathology, and transcriptome sequencing.

(1) At the taxonomic levels of genus and species, there were significant differences in the α-diversity of the microbiome between HCs and NMOSD patients in the acute phase, with NMOSD patients having higher species diversity. (2) In the acute phase, the gut microbiota of NMOSD patients was characterized by Ruminococcaceae_unclassified, Campylobacter, Parabacteroides, Lactobacillus, Akkermansia, Streptococcus oralis, Clostridium leptum, Clostridium asparagiforme, Firmicutes bacterium CAG 238, and Lactobacillus fermentum. (3) The relative abundances of Coprobacter, Turicimonas, Gemmiger, Enterobacter, Roseburia sp.CAG 471, Veillonella tobetsuensis, Proteobacteria bacterium CAG 139, Ruminococcus bicirculans, Lactococcus lactis, Flavonifractor plautii, and Streptococcus cristatus were notably lower in patients experiencing remission compared to NMOSD patients in the acute phase, On the other hand, the relative abundances of Flavonifractor (P = 0.049) and Clostridium aldenense (P = 0.049) were significantly higher. Following medication, the gut microbiome distribution in NMOSD patients during remission closely resembled that of healthy controls (HCs). (4) Compared with HCs, acetate levels in the feces of patients with NMOSD in the acute phase were significantly lower. (5) In addition, we transplanted feces from NMOSD patients into germ-free mice and revealed a significant increase in the levels of IL-6, IL-17A, and IL-23 in the blood of mice belonging to the NMOSD fecal transplantation (NFMT) group. Additionally, the IL-10 level exhibited a significant reduction. Moreover, the proportion of Th17 cells displayed a significant increase, while the proportion of Treg cells exhibited a significant decrease in the spleens of NFMT mice.

Patients in the acute phase of neuromyelitis optica spectrum disorder (NMOSD) exhibited imbalances in their gut microbiota and a deficiency in short-chain fatty acids (SCFAs). Following drug treatment, the composition of intestinal microbes in NMOSD patients during the remission phase closely resembled that of the healthy control population. The FMT experiment provided evidence of the significant association between intestinal flora and the pathogenesis of NMOSD. Consequently, investigating gut microbiota and identifying novel microbial markers hold promise for the diagnosis and treatment of NMOSD patients.

Over the past two decades, as the importance of gut microbiota to human health has become widely known, attempts have been made to treat diseases by correcting dysbiosis of gut microbiota through fecal microbiota transplantation (FMT). Apart from current knowledge of gut microbiota, FMT to treat disease has a long history, from the treatment of food poisoning in the fourth century to the treatment of Clostridioides difficile infections in the twentieth century. In 2013, FMT was recognized as a standard treatment for recurrent C. difficile because it consistently showed high efficacy. Though recurrent C. difficile is the only disease internationally recognized for FMT efficacy, FMT has been tested for other diseases and shown some promising preliminary results. Different FMT methods have been developed using various formulations and administration routes. Despite advances in FMT, some issues remain to be resolved, such as donor screening, manufacturing protocols, and unknown components in the fecal microbiota. In this review, we discuss the mechanisms, clinical indications, methods, and challenges of current FMT. We also discuss the development of alternative therapies to overcome the challenges of FMT.

The understanding of the potential role of the microbiota in the pathogenesis of inflammatory bowel disease (IBD) is ever-evolving. Traditionally, the management of IBD has involved medical therapy and/or surgical intervention. IBD can be characterized by gut microbiome alterations through various pathological processes. Various studies delve into nontraditional methods such as probiotics and fecal microbiota transplant and their potential therapeutic effects. Fecal microbiota transplant involves the delivery of a balanced composition of gut microorganisms into an affected patient via multiple possible routes and methods, while probiotics consist of live microorganisms given via the oral route. At present, neither method is considered first-line treatment, however, fecal microbiota transplant has shown potential success in inducing and maintaining remission in ulcerative colitis. In a study by Kruis and colleagues, Escherichia coli Nissle 1917 was considered to be equivalent to mesalamine in mild ulcerative colitis. Alteration of the microbiome in the management of Crohn's disease is less well defined. Furthermore, variation in the clinical usefulness of 5-aminosalicylic acid medication has been attributed, in part, to its acetylation and inactivation by gut microbes. In summary, our understanding of the microbiome's role is continually advancing, with the possibility of paving the way for personalized medicine based on the microbiome.

Treatments targeting the gut-brain axis (GBA) are effective at reducing symptom burden in irritable bowel syndrome (IBS). The prevalence of common mental disorders and IBS-type symptom reporting is significantly higher in inflammatory bowel disease (IBD) than would be expected, suggesting potential GBA effects in this setting. Manipulation of the GBA may offer novel treatment strategies in selected patients with IBD. We present a narrative review of the bi-directional effects of the GBA in IBD and explore the potential for GBA-targeted therapies in this setting.

We searched MEDLINE, EMBASE, EMBASE Classic, PsychINFO, and the Cochrane Central Register of Controlled Trials for relevant articles published by March 2024.

The bi-directional relationship between psychological well-being and adverse longitudinal disease activity outcomes, and the high prevalence of IBS-type symptom reporting highlight the presence of GBA-mediated effects in IBD. Treatments targeting gut-brain interactions including brain-gut behavioural treatments, neuromodulators, and dietary interventions appear to be useful adjunctive treatments in a subset of patients.

Psychological morbidity is prevalent in patients with IBD. The relationship between longitudinal disease activity outcomes, IBS-type symptom reporting, and poor psychological health is mediated via the GBA. Proactive management of psychological health should be integrated into routine care. Further clinical trials of GBA-targeted therapies, conducted in selected groups of patients with co-existent common mental disorders, or those who report IBS-type symptoms, are required to inform effective integrated models of care in the future.

The incidence of inflammatory bowel diseases [IBD] has risen over the past decade to become a global issue. The objectives of this review were to describe the incidence and/or prevalence of IBD in the era of advanced therapies, and to describe the association between environmental risk factors and both pathogenesis and disease course across the ages.

We performed a search of English language publications listed in PubMed regarding the epidemiology of IBD and key environmental factors implicated in IBD from January 2000 to December 2023.

Annual incidence rates varied by geographical region with IBD estimates ranging from 10.5 to 46.14 per 100 000 in Europe, 1.37 to 1.5 per 100 000 in Asia and the Middle East, 23.67 to 39.8 per 100 000 in Oceania, 0.21 to 3.67 per 100 000 in South America, and 7.3 to 30.2 per 100 000 in North America. The burden of IBD among children and adolescents, and older people is rising globally. Key environmental factors implicated in IBD pathogenesis include exposure to tobacco smoking, antibiotics, non-steroidal anti-inflammatory drugs, oral contraceptives, infections, and ultra-high processed foods. Breastfeeding and a high-quality diet rich in fruit, vegetables, fish, and other fibre sources are important protective factors. Smoking has consistently been shown to negatively impact disease outcomes for Crohn's disease.

The epidemiology of IBD has undergone considerable change in recent decades, with an increase in the burden of disease worldwide. Optimally studying and targeting environmental triggers in IBD may offer future opportunities for disease modification.

The mammalian intestine is colonized by trillions of microorganisms that are collectively referred to as the gut microbiota. The majority of symbionts have co-evolved with their host in a mutualistic relationship that benefits both. Under certain conditions, such as in Crohn's disease, a subtype of inflammatory bowel disease, some symbionts bloom to cause disease in genetically susceptible hosts. Although the identity and function of disease-causing microorganisms or pathobionts in Crohn's disease remain largely unknown, mounting evidence from animal models suggests that pathobionts triggering Crohn's disease-like colitis inhabit certain niches and penetrate the intestinal tissue to trigger inflammation. In this Review, we discuss the distinct niches occupied by intestinal symbionts and the evidence that pathobionts triggering Crohn's disease live in the mucus layer or near the intestinal epithelium. We also discuss how Crohn's disease-associated mutations in the host disrupt intestinal homeostasis by promoting the penetration and accumulation of pathobionts in the intestinal tissue. Finally, we discuss the potential role of microbiome-based interventions in precision therapeutic strategies for the treatment of Crohn's disease.

Gut microbiota provides an important insight into clarifying the mechanism of active substances with low bioavailability, but its specific action mechanism varied case by case and remained unclear. Dihydroquercetin (DHQ) is a bioactive flavonoid with low bioavailability, which showed beneficial effects on colitis alleviation and gut microbiota modulation. Herein, we aimed to explore the microbiota-dependent anticolitis mechanism of DHQ in sight of gut microbiota metabolites and their interactions with microRNAs (miRNAs). Dietary supplementation of DHQ alleviated dextran sulfate sodium-induced colitis phenotypes and improved gut microbiota dysbiosis. Fecal microbiota transplantation further revealed that the anticolitis activity of DHQ was mediated by gut microbiota. To clarify how the modulated gut microbiota alleviated colitis in mice, the tandem analyses of the microbiome and targeted metabolome were performed, and altered profiles of metabolite short-chain fatty acids (SCFAs) and bile acids and their producers were observed in DHQ-treated mice. In addition, SCFA treatment showed anticolitis activity compared to that of bile acids, along with the specific inhibition on the phosphoinositide-3-kinase (PI3K)-protein kinase B (Akt) pathway. Subsequently, the colonic miRNA profile of mice receiving SCFA treatment was sequenced, and a differentially expressed miR-10a-5p was identified. Both prediction analysis and dual-luciferase reporter assay indicated that miR-10a-5p directly bind to the 3'-untranslated regions of gene pik3ca, inhibit the PI3K-Akt pathway activation, and lead to colitis alleviation. Together, we proposed that gut microbiota mediated the anticolitis activity of DHQ through the SCFAs/miR-10a-5p/PI3K-Akt axis, and it provided a novel insight into clarifying the microbiota-dependent mechanism via the interaction between metabolites and miRNAs.

Despite the availability of numerous treatments for Crohn disease, there are patients who do not respond to any therapy, thereby diminishing their quality of life. The aim of this review is to analyze the efficacy and safety of autologous hematopoietic stem cell transplantation therapy for refractory Crohn disease.

This work is a systematic review with meta-analysis conducted in accordance with the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analyses. Electronic databases such as PubMed, Scopus, Web of Science, and ClinicalTrials were consulted. The searches were carried out in August 2024. To evaluate the efficacy of autologous hematopoietic stem cell transplantation in inducing remission, the mean and standard deviation of the Crohn's Disease Activity Index pre- and post- treatment were used, and a fixed-effects meta-analysis was conducted. Additionally, to assess the efficacy in perianal fistulas, a random-effects meta-analysis was performed, collecting data on the number of subjects with fistulas at the beginning and end of the intervention. All 95% confidence intervals were calculated, and the I2 statistic was used to assess the heterogeneity of the outcome variables.

A total of 609 records were identified from databases, with 12 studies selected for inclusion in the review. Immediate intervention proved effective in inducing a decrease in the Crohn Disease Activity Index compared to late intervention with conventional therapies. Moreover, the meta-analysis demonstrated efficacy for Crohn disease and associated fistulas with a mean decrease in the CDAI of -217.53 ± 14.3. When evaluating the efficacy of the procedure in perianal fistulas, a risk ratio of 0.47 with a 95% CI of [0.26, 0.86] was obtained. However, the procedure showed adverse effects, such as infections, acute renal failure or deaths.

Systemic autologous hematopoietic stem cell transplantation has shown efficacy in patients who fail to achieve remission of their Crohn disease with conventional therapies. This procedure has also demonstrated efficacy in treating perianal fistulas. However, it is essential to carefully evaluate de implementation of this procedure due to the associated risks.

The complex network of factors that contribute to neurodegeneration have hampered the discovery of effective preventative measures. While much work has focused on brain-first therapeutics, it is becoming evident that physiological changes outside of the brain are the best target for early interventions. Specifically, myeloid cells, including peripheral macrophages and microglia, are a sensitive population of cells whose activity can directly impact neuronal health. Myeloid cell activity includes cytokine production, migration, debris clearance, and phagocytosis. Environmental measures that can modulate these activities range from toxin exposure to diet. However, one of the most influential mediators of myeloid fitness is the gut microenvironment. Here, we review the current data about the role of myeloid cells in gastrointestinal disorders, Parkinson's disease, dementia, and multiple sclerosis. We then delve into the gut microbiota modulating therapies available and clinical evidence for their use in neurodegeneration. Modulating lifestyle and environmental mediators of inflammation are one of the most promising interventions for neurodegeneration and a systematic and concerted effort to examine these factors in healthy aging is the next frontier.

There has been an increased ability to investigate the human microbiota through next-generation sequencing and functional assessment. This advancement has rapidly expanded our ability to study and manipulate the gastrointestinal microbiome to mitigate disease. Fecal microbiota transplantation, a therapy that broadly transfers the entire intestinal ecosystem, has been explored as a potential therapeutic in a variety of gastrointestinal, hepatic, and extraintestinal conditions. The field, however, continues to evolve, with a movement toward precision microbiome therapeutics, individualizing care for various disorders. This review will describe the use of fecal microbiota transplantation, microbiota restoration, and precision microbiome therapeutics, focusing on gastrointestinal and hepatic diseases.

Goblet cells (GCs) are specialised guardians lining the intestine. They play a critical role in gut defence and immune regulation. GCs continuously secrete mucus creating a physical barrier to protect from pathogens while harbouring symbiotic gut bacteria adapted to live within the mucus. GCs also form specialised GC-associated passages in a dynamic and regulated manner to deliver luminal antigens to immune cells, promoting gut tolerance and preventing inflammation. The composition of gut bacteria directly influences GC function, highlighting the intricate interplay between these components of a healthy gut. Indeed, imbalances in the gut microbiome can disrupt GC function, contributing to various gastrointestinal diseases like colorectal cancer, inflammatory bowel disease, cystic fibrosis, pathogen infections and liver diseases. This review explores the interplay between GCs and the immune system. We delve into the underlying mechanisms by which GC dysfunction contributes to the development and progression of gastrointestinal diseases. Finally, we examine current and potential treatments that target GCs and represent promising avenues for further investigation.

The deleterious effects of human activities on biodiversity in the vegetal and animal world, and on climate changes are now well-established facts. However, little is yet known on the impact of human activities on microbial diversity on the planet and more specifically on the human microbiota Large implementation of metagenomics allows exaustive microbial cataloguing with broad spatio-temporal resolution of human microbiota. A reduction in bacterial richness and diversity in the human microbiota, particularly in the intestinal tract, is now established and particularly obvious in the most industrialized regions of the planet. Massive, uncontrolled use of antibiotics, drastic changes in traditional food habits and some elements of the "global exposome" that remain to identify are usually considered as stressors accounting for this situation of "missing microbes". As a consequence, a dysbiotic situation develops, a "dysbiosis" being characterized by the erosion of the central core of shared bacterial species across individuals and the development of opportunistic "pathobionts" in response to a weaker barrier capacity of these impoverished microbiota. The current challenge is to establish a causality link between the extension of these dysbiotic situations and the steady emergence of epidemic, non-communicable diseases such as asthma, allergy, obesity, diabetes, autoimmune diseases and some cancers. Experimental animal models combined with controlled, prospective clinical interventions are in demand to consolidate causality links, with the understanding that in the deciphering of the mechanisms of alteration of the human-microbiome symbiosis resides a novel exciting chapter of medicine: "microbial medicine".

Shizao decoction (SZD) consisted of Euphorbia kansui (EK), Euphorbia pekinensis (EP), Daphne genkwa (DG), and Fructus Jujubae (FJ) is a classic Chinese herbal medicine formula for treating malignant ascites, which is closely related to the modulation of gut microbiota by our previous study. For water-expelling members (WEM) including EK, EP, and DG may have side effects on the intestine, FJ is employed for detoxification and effectivity enhancement of WEM. However, the underlying mechanism for the compatibility of WEM and FJ is still unknown.

To investigate the effect of the compatibility of WEM with FJ in SZD on malignant ascites and elucidate the potential mechanism from the perspective of the modulation of gut microbiota and related metabolic function.

Qualitative and quantitative evaluation of main components was conducted for comprehensive characterization of SZD and WEM. The effect of WEM and SZD was compared on malignant ascites effusion (MAE) rats. The intestinal injury was evaluated by HE staining and oxidative damage. Ascites weight, urine amount, fecal water content, the expression of aquaporins, and cytokines in ascites (IL-6, VEGF, and TNF-α) were measured to estimate the water-expelling activity. The intestinal flora was detected by 16S rDNA sequencing and the content of fecal short-chain fatty acids (SCFAs) was analyzed using gas chromatography-mass spectrometry. Pseudo-germ-free (PGF) and fecal bacteria transplantation animal experiments were subsequently employed to validate this finding. The fecal metabolomics and correlation analysis were finally conducted to explore the related metabolic changes.

51 and 33 components were identified in SZD and WEM, respectively. Compared to WEM alone, the compatibility with FJ remarkably reduced intestinal oxidative damage in MAE rats. Ascites was also relieved by downregulating the expression of AQP3 in the colon and decreasing the levels of IL-6, TNF-α and VEGF in ascites. The diversity of gut microbiota was reversed with an increase in Lactobacillus and Clostridia_UCG-014 while a decrease in Colidextribacter. Under the PGF condition, compatibility of WEM with FJ failed to reduce intestinal injury and alleviate MA significantly, but this effect was further enhanced after FMT. 23 potential fecal metabolites were finally identified. Correlation analysis further showed that Lactobacillus and Clostridia_UCG-014 were positively correlated with SCFAs and l-tryptophan. Colidextribacter was negatively correlated with thymidine but positively correlated with ursodeoxycholic acid and deoxycholic acid.

FJ cooperated with WEM reduced intestinal injury and alleviated malignant ascites by modulating gut microbiota, short-chain fatty and tryptophan metabolism. These findings provide a scientific basis for the clinical application of FJ from SZD and the safe usage of SZD.

The human gastrointestinal (GI) tract microbiome is a complex and all-encompassing ecological system of trillions of microorganisms. It plays a vital role in digestion, disease prevention, and overall health. When this delicate balance is disrupted, it can lead to various health issues. Fecal microbiota transplantation (FMT) is an emerging therapeutic intervention used as an adjuvant therapy for many diseases, particularly those with dysbiosis as their underlying cause. Its goal is to restore this balance by transferring fecal material from healthy donors to the recipients. FMT has an impressive reported cure rate between 80% and 90% and has become a favored treatment for many diseases. While FMT may have generally mild to moderate transient adverse effects, rare severe complications underscore the importance of rigorous donor screening and standardized administration. FMT has enormous potential as a practical therapeutic approach; however, additional research is required to further determine its potential for clinical utilization, as well as its safety and efficiency in different patient populations. This comprehensive literature review offers increased confidence in the safety and effectiveness of FMT for several diseases affecting the intestines and other systems, including diabetes, obesity, inflammatory and autoimmune illness, and other conditions.

Background: The gut microbiome plays a crucial role in human health, and recent research has highlighted its potential impact on ocular health through the gut-eye axis. Dysbiosis, or an imbalance in the gut microbiota, has been implicated in various ocular diseases. Methods: A comprehensive literature search was conducted using relevant keywords in major electronic databases, prioritizing recent peer-reviewed articles published in English. Results: The gut microbiota influences ocular health through immune modulation, maintenance of the blood-retinal barrier, and production of beneficial metabolites. Dysbiosis can disrupt these mechanisms, contributing to ocular inflammation, tissue damage, and disease progression in conditions such as uveitis, age-related macular degeneration, diabetic retinopathy, dry eye disease, and glaucoma. Therapeutic modulation of the gut microbiome through probiotics, prebiotics, synbiotics, and fecal microbiota transplantation shows promise in preclinical and preliminary human studies. Conclusions: The gut-eye axis represents a dynamic and complex interplay between the gut microbiome and ocular health. Targeting the gut microbiome through innovative therapeutic strategies holds potential for improving the prevention and management of various ocular diseases.

Psoriasis (PS) and inflammatory bowel disease (IBD) are immune-mediated chronic conditions that share pathophysiological processes, including immune system dysfunction, microbiome dysbiosis, and inflammatory pathways. These pathways result in increased turnover of epithelial cells and compromised barrier function. The assessment of the literature suggests that immunopathogenic mechanisms, such as tumor necrosis factor (TNF)-α signaling and IL-23/IL-17 axis dysregulation, are shared by PS and IBD. Clinical characteristics and diagnostic approaches overlap significantly, and advances in biomarker identification benefit both conditions. Current treatments, namely biologics that target TNF-α, IL-17, and IL-23, show promising results in decreasing inflammation and controlling symptoms. Precision medicine approaches are prioritized in prospective therapeutic procedures to tailor pharmaceuticals based on specific biomarkers, perhaps improving outcomes and minimizing side effects. This study thoroughly examines and evaluates the body of research on PS and IBD. Several papers were examined to compile data on clinical features, diagnosis, therapies, pathophysiology, epidemiology, and potential future therapeutic developments. The selection of articles was based on three methodological qualities: relevance and addition to the knowledge of IBD and PS. The retrieved data were combined to provide a coherent summary of the state of the knowledge and to spot new trends. The overview of the latest studies demonstrates that both PS and IBD share pathophysiological foundations and therapeutic approaches. With a spotlight on particular biomarkers, advances in precision medicine provide a promising path toward enhancing therapeutic effectiveness and minimizing side effects.

Novel technologies offer insights into the potential role of the intestinal microbiota in human health and disease. Dysbiosis has been associated with several diseases, and it is thought to play a role in the pathogenesis of different gastrointestinal diseases. Faecal microbiota transplantation (FMT) is emerging as a method to modulate the gastrointestinal microbial ecosystem. While recurrent Clostridioides difficile infection is the recognised FMT indication, exploration of other therapeutic uses is ongoing.

Following PRISMA guidelines, we conducted a systematic review, extracting 583 articles from Embase and PubMed (index date to October 2022).

The search yielded 58 studies for full review, with 50 included in the systematic review. Articles were categorised by FMT indication, study design, efficacy, adverse events, donor selection and administration route. FMT appears safe and effective for recurrent Clostridioides difficile infection, although severe adverse events are reported in children. However, there are currently insufficient data to support the use of FMT for other potential therapeutic indications (such as irritable or inflammatory bowel disease or obesity), beside the potential to decolonise multi-drug resistant organisms.

This underscores the need for randomised, controlled, prospective cohort studies in children to assess FMT effectiveness in diverse conditions and counteract publication bias.

Colorectal cancer (CRC) is a worldwide public health issue specifically in patients with chronic diseases associated with a western lifestyle, such as metabolic diseases and inflammatory bowel diseases (IBD). Interestingly, both metabolic disorders and IBD are characterized by a chronic state of inflammation that contributes to the carcinogenesis with specific alteration of the gut microbiota composition and function. Evidence now shows that this altered gut microbiota contributes fueling a chronic pro-inflammatory state in a vicious circle that can favor CRC development. In this review article, we present the current knowledge concerning the involvement of the gut microbiota as a procarcinogenic factor shared by IBD and cardiometabolic diseases, and provide clues as to how it may be used to prevent or diagnose CRC.

Gut microbiota dysbiosis has a critical role in the pathogenesis of inflammatory bowel diseases, prompting the exploration of novel therapeutic approaches like fecal microbiota transplantation, which involves the transfer of fecal microbiota from a healthy donor to a recipient with the aim of restoring a balanced microbial community and attenuating inflammation. Fecal microbiota transplantation may exert beneficial effects in inflammatory bowel disease through modulation of immune responses, restoration of mucosal barrier integrity, and alteration of microbial metabolites. It could alter disease course and prevent flares, although long-term durability and safety data are lacking. This review provides a summary of current evidence on fecal microbiota transplantation in inflammatory bowel disease management, focusing on its challenges, such as variability in donor selection criteria, standardization of transplant protocols, and long-term outcomes post-transplantation.