Alpha-defensin 1 is a small antimicrobial peptide that acts as the first line of defense against pathogens. It is induced following microbial cues and inflammatory signals in neutrophils and Paneth cells in the small intestine, which suggests that it plays a role in microbial homeostasis in the gut. The gut microbial products also serve as ligands for the aryl hydrocarbon receptor (AhR), an environmental sensor. In the current study, we investigated if there is any crosstalk between AhR and alpha-defensin 1. Interestingly, we found a positive correlation between AhR and alpha-defensin 1 protein levels in ileal tissues from active Crohn's' (CD) patients and epithelial cells (IECs) from multiple models of murine colitis. In vitro downregulation of AhR led to inhibition of α-defensin 1, while activation of AhR induced α-defensin 1 in IECs. AhR directly targeted the dioxin response element 3 (DRE3) region on the α-defensin 1 promoter in IECs. AhR-mediated induction of α-defensin 1 in colitis mice reversed the gut microbial dysbiosis and alleviated colitis. Our data identify a novel signaling pathway in which AhR acts as a transcription factor for α-defensin 1, leading to regulation of homeostasis between gut microbiota, intestinal mucosa, and mucosal immunity.

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.

Inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), lacks a known etiology. Although clinical symptoms, imaging, and colonoscopy are common diagnostic tools, fecal calprotectin (FC) serves as a widely used biomarker to track disease activity. Metabolomics, within the omics sciences, holds promise for identifying disease progression biomarkers. This approach involves studying metabolites in biological media to uncover pathological factors.

The purpose of this study was to explore fecal metabolomics in IBD patients, evaluate its potential in differentiating subtypes, and assess disease activity using FC.

Cross-sectional study including IBD patients, clinical data, and FC measurements (=200 μg/g as an indicator of active disease).

Fecal metabolomics utilized chromatography mass spectrometry/solid phase microextraction with MetaboAnalyst 5.0 software for analysis. Of 52 patients (29 UC, 23 CD), 36 (69.2%) exhibited inflammatory activity. We identified 56 fecal metabolites, with hexadecanoic acid, squalene, and octadecanoic acid notably distinguishing CD from UC. For UC, octadecanoic and hexadecanoic acids correlated with disease activity, whereas octadecanoic acid was most relevant in CD.

These findings highlight the potential of metabolomics as a noninvasive complement for evaluating IBD, aiding diagnosis, and assessing disease activity.

Numerous recent studies have suggested that the composition of the intestinal microbiota can trigger metabolic disorders, such as diabetes, prediabetes, obesity, metabolic syndrome, sarcopenia, dyslipidemia, hyperhomocysteinemia, and non-alcoholic fatty liver disease. Since then, considerable effort has been made to understand the link between the composition of intestinal microbiota and metabolic disorders, as well as the role of probiotics in the modulation of the intestinal microbiota. The aim of this review was to summarize the reviews and individual articles on the state of the art regarding ideal therapy with probiotics and prebiotics in order to obtain the reversion of dysbiosis (alteration in microbiota) to eubiosis during metabolic diseases, such as diabetes, prediabetes, obesity, hyperhomocysteinemia, dyslipidemia, sarcopenia, and non-alcoholic fatty liver diseases. This review includes 245 eligible studies. In conclusion, a condition of dysbiosis, or in general, alteration of the intestinal microbiota, could be implicated in the development of metabolic disorders through different mechanisms, mainly linked to the release of pro-inflammatory factors. Several studies have already demonstrated the potential of using probiotics and prebiotics in the treatment of this condition, detecting significant improvements in the specific symptoms of metabolic diseases. These findings reinforce the hypothesis that a condition of dysbiosis can lead to a generalized inflammatory picture with negative consequences on different organs and systems. Moreover, this review confirms that the beneficial effects of probiotics on metabolic diseases are promising, but more research is needed to determine the optimal probiotic strains, doses, and administration forms for specific metabolic conditions.

A cohort of patients with inflammatory bowel disease (IBD) exhibit expansion of the gut pathobiont, adherent-invasive E. coli (AIEC). Loss of activity of the IBD susceptibility gene, protein tyrosine phosphatase type 2 (PTPN2), results in dysbiosis of the gut microbiota both in human subjects and mice. Further, constitutive Ptpn2 knock-out (Ptpn2-KO) mice display expansion of AIEC compared to wildtype littermates. CEACAM6, a host cell surface glycoprotein, is exploited by AIEC to attach to and enter intestinal epithelial cells (IECs). Here, we investigate the role of IEC-specific PTPN2 in restricting AIEC invasion.

Biopsies from IBD patients heterozygous (CT) or homozygous (CC) for the PTPN2 SNP (single nucleotide polymorphism) rs1893217 were processed for immunohistochemistry. HT-29 intestinal epithelial cells (IEC) were transfected with control shRNA (PTPN2-CTL), or a shRNA targeted towards PTPN2 (PTPN2-KD). The rs1893217 SNP was inserted (PTPN2-KI), or a complete knock-out of PTPN2 (PTPN2-KO) was generated, with CRISPR-Cas9 gene editing of Caco-2BBe IEC lines. Adherence and invasion assays were performed with either the human IBD AIEC isolate, LF82, or a novel fluorescent-tagged mouse adherent-invasive E. coli (mAIECred) at multiplicity of infection (MOI) of 10. IL-6 and the pan-JAK inhibitor tofacitinib were administered to interrogate JAK-STAT signaling. Protein expression was determined by western blotting and densitometry.

CEACAM6 expression was elevated (colon and ileum) in IBD patients carrying the PTPN2 rs1893217 SNP (CT, CC) compared to wildtype (TT) IBD patients. HT-29 and Caco-2BBe cell lines deficient in PTPN2 expressed significantly higher levels of CEACAM6. Further, PTPN2-KI and PTPN2-KO cell lines also displayed greater adherence and invasion by AIEC LF82 and higher mAIECred invasion. CEACAM6 expression was further elevated after administration of IL-6 in PTPN2-deficient cell lines compared to untreated controls. Silencing of STAT1 and 3 partially reduced CEACAM6 protein expression. Tofacitinib significantly reduced the elevated CEACAM6 protein expression and the higher AIEC adherence and invasion in PTPN2-KI and PTPN2-KO cell lines compared to DMSO controls.

Our findings highlight a crucial role for PTPN2 in restricting pathobiont entry into host cells. Our study also describes a role for the FDA-approved drug, tofacitinib (Xeljanz) in correcting the JAK-STAT-mediated over-expression of CEACAM6, used by pathobionts as an entry portal into host cells. These findings suggest a role for JAK-inhibitors in mitigating AIEC colonization in IBD-susceptible hosts.

Idiopathic granulomatous mastitis (IGM) is a rare inflammatory breast disease that can be clinically and radiologically mistaken for carcinoma. Although its etiology remains uncertain, potential associations with pregnancy, lactation, hormonal imbalances, autoimmunity, smoking, and various microorganisms have been suggested. This study aimed to evaluate the relationship between IGM and oral health. We included 42 female patients diagnosed with IGM based on histopathological evaluations conducted between September 2018 and October 2023. The reference group consisted of 47 female patients with clinically, radiologically, and laboratory-proven non-specific mastitis and 36 healthy female individuals. The oral health of all participants was evaluated by an experienced dentist using the "Decayed, Missing and Filled Teeth" (DMFT) index and the "Simplified Oral Hygiene Index" (OHI-S). The ages of IGM patients included in this study ranged from 29 to 51 years, with a mean age of 34.88 ± 4.87 years. The most common clinical findings were pain (n = 38), palpable breast mass, erythema, induration, and dermal sinus. Comparison of the OHI-S and DMFT index values among participants revealed that those diagnosed with IGM had significantly higher values than those in the reference group (P < 0.05). Our findings suggest a potential involvement of poor oral health in the etiology of IGM. Future studies should consider oral health as a factor in IGM etiology and explore the oral microbiota in samples obtained from the affected tissue.

While significant research exists on gut microbiota changes after anti-tumor necrosis factor-alpha (anti TNF-α) therapy for ulcerative colitis, little is known about the longitudinal changes related to the effects of anti TNF-α. This study aimed to investigate the dynamics of gut microbiome changes during anti TNF-α (adalimumab) therapy in patients with ulcerative colitis (UC).

The microbiota composition was affected by the disease severity and extent in patients with UC. Regardless of clinical remission status at each time point, patients with UC exhibited microbial community distinctions from healthy controls. Distinct amplicon sequence variants (ASVs) differences were identified throughout the course of Adalimumab (ADA) treatment at each time point. A notable reduction in gut microbiome dissimilarity was observed only in remitters. Remitters demonstrated a decrease in the relative abundances of Burkholderia-Caballeronia-Paraburkholderia and Staphylococcus as the treatment progressed. Additionally, there was an observed increase in the relative abundances of Bifidobacterium and Dorea. Given the distribution of the 48 ASVs with high or low relative abundances in the pre-treatment samples according to clinical remission at week 8, a clinical remission at week 8 with a sensitivity and specificity of 72.4% and 84.3%, respectively, was predicted on the receiver operating characteristic curve (area under the curve, 0.851).

The gut microbiota undergoes diverse changes according to the treatment response during ADA treatment. These changes provide insights into predicting treatment responses to ADA and offer new therapeutic targets for UC.

The gut microbiota represents a complex ecosystem of trillions of microorganisms residing in the human gastrointestinal tract, which is known to interact with the host physiology and regulate multiple functions. Alterations in gut microbial composition, diversity, and function are referred to as dysbiosis. Dysbiosis has been associated with a variety of chronic diseases, including Clostridioides difficile infections, but also cardiometabolic diseases, including obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM). The implication of gut microbiota dysbiosis in the pathogenesis of both obesity and T2DM has paved the way to implementing novel therapeutic approaches for metabolic diseases through gut microbial reconfiguration. These interventions include probiotics, prebiotics, and synbiotics, while a more innovative approach has been fecal microbiota transplantation (FMT). FMT is a procedure that delivers healthy human donor stool to another individual through the gastrointestinal tract, aiming to restore gut microbiota balance. Several studies have investigated this approach as a potential tool to mitigate the adverse metabolic effects of gut microbiota aberrations associated with obesity and T2DM. The aim of the present review was to critically summarize the existing evidence regarding the clinical applications of FMT in the management of obesity and T2DM and provide an update on the potential of this method to remodel the entire host microbiota, leading thus to weight loss and sustained metabolic benefits. Safety issues, long-term efficacy, limitations, and pitfalls associated with FMT studies are further discussed, emphasizing the need for further research and standardization in certain methodological aspects in order to optimize metabolic outcomes.

Current therapy for patients suffering from inflammatory bowel diseases (IBD) is focused on inflammatory mechanisms exclusively and not the dysbiotic microbiota, despite growing evidence implicating a role for intestinal microbes in disease.

Ongoing research into the intestinal microbiota of IBD patients, using new technologies and/or deeper application of existing ones, has identified a number of microorganisms whose properties and behaviors warrant consideration as causative factors in disease. Such studies have implicated both bacteria and fungi in the pathogenesis of disease. Some of these organisms manifest mechanisms that should be amenable to therapeutic intervention via either conventional or novel drug discovery platforms. Of particular note is a deeper characterization of microbial derived proteases and their destructive potential.

Given the steady progress on the mechanistic role of the microbiota in inflammatory diseases, it is reasonable to anticipate a future in which therapeutics targeting microbial derived pathogenic factors play an important role in improving the lives of IBD patients.

Probiotics are "live microorganisms which, when administered in adequate amount, confer health benefits on the host". They can be found in certain foods like yogurt and kefir and in dietary supplements. The introduction of bacterial derivatives has not only contributed to disease control but has also exhibited promising outcomes, such as improved survival rates, immune enhancement, and growth promotion effects. It is interesting to note that the efficacy of probiotics goes beyond the viability of the bacteria, giving rise to concepts like paraprobiotics, non-viable forms of probiotics, and postbiotics. Paraprobiotics offer various health benefits in children with intestinal dysbiosis, contributing to improved digestive health, immune function, and overall well-being. In this review, the potential of these therapeutic applications as alternatives to pharmacological agents for treating pediatric intestinal dysbiosis will be thoroughly evaluated. This includes an analysis of their efficacy, safety, long-term benefits, and their ability to restore gut microbiota balance, improve digestive health, enhance immune function, and reduce inflammation. The aim is to determine if these non-pharmacological interventions can effectively and safely manage intestinal dysbiosis in children, reducing the need for conventional medications and their side effects.

Bowel strictures are well recognized as one of the most severe complications in Crohn's disease, with variable impacts on the prognosis and often needing surgical or endoscopic treatment. Distinguishing inflammatory strictures from fibrotic ones is of primary importance due to the different therapeutic approaches required. Indeed, to better understand the pathogenesis of fibrosis, it is crucial to investigate molecular processes involving genetic factors, cytokines, alteration of the intestinal barrier, and epithelial and endothelial damage, leading to an increase in extracellular matrix synthesis, which ultimately ends in fibrosis. In such a complex mechanism, the gut microbiota also seems to play a role. A better comprehension of molecular processes underlying bowel fibrosis, in addition to radiological and histopathological findings, has led to the identification of high-risk patients for personalized follow-up and testing of new therapies, primarily in preclinical models, targeting specific pathways involving Transforming Growth Factor-β, interleukins, extracellular matrix balance, and gut microbiota. Our review aims to summarize current evidence about molecular factors involved in intestinal fibrosis' pathogenesis, paving the way for potential diagnostic biomarkers or anti-fibrotic treatments for stricturing Crohn's disease.

Diet plays an integral role in the modulation of the intestinal environment, with the potential to be modified for management of individuals with inflammatory bowel disease [IBD]. It has been hypothesised that poor 'Western-style' dietary patterns select for a microbiota that drives IBD inflammation and, that through dietary intervention, a healthy microbiota may be restored. This study aimed to systematically review the literature and assess current available evidence regarding the influence of diet on the intestinal microbiota composition in IBD patients, and how this may affect disease activity.

MEDLINE, EMBASE, Scopus, Web of Science, and Cochrane Library were searched from January 2013 to June 2023, to identify studies investigating diet and microbiota in IBD.

Thirteen primary studies met the inclusion criteria and were selected for narrative synthesis. Reported associations between diet and microbiota in IBD were conflicting due to the considerable degree of heterogeneity between studies. Nine intervention studies trialled specific diets and did not demonstrate significant shifts in the diversity and abundance of intestinal microbial communities or improvement in disease outcomes. The remaining four cross-sectional studies did not find a specific microbial signature associated with habitual dietary patterns in IBD patients.

Diet modulates the gut microbiota, and this may have implications for IBD; however, the body of evidence does not currently support clear dietary patterns or food constituents that are associated with a specific microbiota profile or disease marker in IBD patients. Further research is required with a focus on robust and consistent methodology to achieve improved identification of associations.

The intestinal tract of humans harbors a dynamic and complex bacterial community known as the gut microbiota, which plays a crucial role in regulating functions such as metabolism and immunity in the human body. Numerous studies conducted in recent decades have also highlighted the significant potential of the gut microbiota in promoting human health. It is widely recognized that training and nutrition strategies are pivotal factors that allow athletes to achieve optimal performance. Consequently, there has been an increasing focus on whether training and dietary patterns influence sports performance through their impact on the gut microbiota. In this review, we aim to present the concept and primary functions of the gut microbiota, explore the relationship between exercise and the gut microbiota, and specifically examine the popular dietary patterns associated with athletes' sports performance while considering their interaction with the gut microbiota. Finally, we discuss the potential mechanisms by which dietary patterns affect sports performance from a nutritional perspective, aiming to elucidate the intricate interplay among dietary patterns, the gut microbiota, and sports performance. We have found that the precise application of specific dietary patterns (ketogenic diet, plant-based diet, high-protein diet, Mediterranean diet, and high intake of carbohydrate) can improve vascular function and reduce the risk of illness in health promotion, etc., as well as promoting recovery and controlling weight with regard to improving sports performance, etc. In conclusion, although it can be inferred that certain aspects of an athlete's ability may benefit from specific dietary patterns mediated by the gut microbiota to some extent, further high-quality clinical studies are warranted to substantiate these claims and elucidate the underlying mechanisms.

This review scrutinizes the intricate interplay between the microbiome and the human body, exploring its multifaceted dimensions and far-reaching implications. The human microbiome, comprising diverse microbial communities inhabiting various anatomical niches, is increasingly recognized as a critical determinant of human health and disease. Through an extensive examination of current research, this review elucidates the dynamic interactions between the microbiome and host physiology across multiple organ systems. Key topics include the establishment and maintenance of microbiota diversity, the influence of host factors on microbial composition, and the bidirectional communication pathways between microbiota and host cells. Furthermore, we delve into the functional implications of microbiome dysbiosis in disease states, emphasizing its role in shaping immune responses, metabolic processes, and neurological functions. Additionally, this review discusses emerging therapeutic strategies aimed at modulating the microbiome to restore host-microbe homeostasis and promote health. Microbiota fecal transplantation represents a groundbreaking therapeutic approach in the management of dysbiosis-related diseases, offering a promising avenue for restoring microbial balance within the gut ecosystem. This innovative therapy involves the transfer of fecal microbiota from a healthy donor to an individual suffering from dysbiosis, aiming to replenish beneficial microbial populations and mitigate pathological imbalances. By synthesizing findings from diverse fields, this review offers valuable insights into the complex relationship between the microbiome and the human body, highlighting avenues for future research and clinical interventions.

Recent advances in understanding how the microbiome can influence both the physiology and the pathogenesis of disease in humans have highlighted the importance of gaining a deeper insight into the complexities of the host-microbial dialogue. In tandem with this progress, has been a greater understanding of the biological pathways which regulate both homeostasis and inflammation at barrier tissue sites, such as the skin and the gut. In this regard, the Interleukin-1 family of cytokines, which can be segregated into IL-1, IL-18 and IL-36 subfamilies, have emerged as important custodians of barrier health and immunity. With established roles as orchestrators of various inflammatory diseases in both the skin and intestine, it is now becoming clear that IL-1 family cytokine activity is not only directly influenced by external microbes, but can also play important roles in shaping the composition of the microbiome at barrier sites. This review explores the current knowledge surrounding the evidence that places these cytokines as key mediators at the interface between the microbiome and human health and disease at the skin and intestinal barrier tissues.

In multiple sclerosis (MS), alterations of the gut microbiota lead to inflammation. However, the role of other microbiomes in the body in MS has not been fully elucidated. In a pilot case-controlled study, we carried out simultaneous characterization of faecal and oral microbiota and conducted an in-depth analysis of bacterial alterations associated with MS. Using 16S rRNA sequencing and metabolic inference tools, we compared the oral/faecal microbiota and bacterial metabolism pathways in French MS patients (n = 14) and healthy volunteers (HV, n = 21). A classification model based on metabolite flux balance was established and validated in an independent German cohort (MS n = 12, HV n = 38). Our analysis revealed decreases in diversity indices and oral/faecal compartmentalization, the depletion of commensal bacteria (Aggregatibacter and Streptococcus in saliva and Coprobacter and Roseburia in faeces) and enrichment of inflammation-associated bacteria in MS patients (Leptotrichia and Fusobacterium in saliva and Enterobacteriaceae and Actinomyces in faeces). Several microbial pathways were also altered (the polyamine pathway and remodelling of bacterial surface antigens and energetic metabolism) while flux balance analysis revealed associated alterations in metabolite production in MS (nitrogen and nucleoside). Based on this analysis, we identified a specific oral metabolite signature in MS patients, that could discriminate MS patients from HV and rheumatoid arthritis patients. This signature allowed us to create and validate a discrimination model on an independent cohort, which reached a specificity of 92%. Overall, the oral and faecal microbiomes were altered in MS patients. This pilot study highlights the need to study the oral microbiota and oral health implications in patients with autoimmune diseases on a larger scale and suggests that knowledge of the salivary microbiome could help guide the identification of new pathogenic mechanisms associated with the microbiota in MS patients.

Obesity is becoming a worldwide pandemic with over one billion people affected. Of women in the United States, who are of childbearing age, two-thirds of them are considered overweight/obese. Offspring of women with obesity have a greater likelihood of developing cardiometabolic disease later in life, therefore making obesity a transgenerational issue. Emerging topics such as maternal microbial dysbiosis with altered levels of bacterial phyla and maternal obesity programming offspring cardiometabolic disease are a novel area of research discussed in this review. In the authors' opinion, beneficial therapeutics will be developed from knowledge of bacterial-host interactions at the most specific level possible. Although there is an abundance of obesity-related microbiome research, it is not concise, readily available, nor easy to interpret at this time. This review details the current knowledge regarding the relationship between obesity and the gut microbiome, with an emphasis on maternal obesity.

Global plastic use has consistently increased over the past century with several different types of plastics now being produced. Much of these plastics end up in oceans or landfills leading to a substantial accumulation of plastics in the environment. Plastic debris slowly degrades into microplastics (MPs) that can ultimately be inhaled or ingested by both animals and humans. A growing body of evidence indicates that MPs can cross the gut barrier and enter into the lymphatic and systemic circulation leading to accumulation in tissues such as the lungs, liver, kidney, and brain. The impacts of mixed MPs exposure on tissue function through metabolism remains largely unexplored.

This study aims to investigate the impacts of polymer microspheres on tissue metabolism in mice by assessing the microspheres ability to translocate across the gut barrier and enter into systemic circulation. Specifically, we wanted to examine microsphere accumulation in different organ systems, identify concentration-dependent metabolic changes, and evaluate the effects of mixed microsphere exposures on health outcomes.

To investigate the impact of ingested microspheres on target metabolic pathways, mice were exposed to either polystyrene (5 μ m ) microspheres or a mixture of polymer microspheres consisting of polystyrene (5 μ m ), polyethylene (1 - 4 μ m ), and the biodegradability and biocompatible plastic, poly-(lactic-co-glycolic acid) (5 μ m ). Exposures were performed twice a week for 4 weeks at a concentration of either 0, 2, or 4 mg / week via oral gastric gavage. Tissues were collected to examine microsphere ingress and changes in metabolites.

In mice that ingested microspheres, we detected polystyrene microspheres in distant tissues including the brain, liver, and kidney. Additionally, we report on the metabolic differences that occurred in the colon, liver, and brain, which showed differential responses that were dependent on concentration and type of microsphere exposure.

This study uses a mouse model to provide critical insight into the potential health implications of the pervasive issue of plastic pollution. These findings demonstrate that orally consumed polystyrene or mixed polymer microspheres can accumulate in tissues such as the brain, liver, and kidney. Furthermore, this study highlights concentration-dependent and polymer type-specific metabolic changes in the colon, liver, and brain after plastic microsphere exposure. These results underline the mobility within and between biological tissues of MPs after exposure and emphasize the importance of understanding their metabolic impact. https://doi.org/10.1289/EHP13435.

In both Crohn's disease (CD) and ulcerative colitis (UC), the two major forms of inflammatory bowel disease (IBD) the immune reaction is - at least partially - directed against components of the luminal microbiota of the gut. These immune responses as well as other factors contribute to a phenomenon frequently described as "dysbiosis" meaning an alteration of the composition of the colonic microbiota. To improve the dysbiosis and to restore the normal composition of the colonic microbiota, fecal microbiota transplantation (FMT) has been tested as a therapeutic option to induce and maintain remission in IBD patients.

This review will first discuss changes in the composition of the intestinal microbiota found in IBD patients and second the therapeutic potential of microbiological interventions for the treatment of these patients. FMT has been studied in several clinical trials in both, CD and UC. Reported results and subsequent meta-analyses indicate that FMT may be effective to induce remission in UC. However, the optimal route of FMT, the necessary number of administrations and the question whether life bacteria of freshly prepared stool is more effective than frozen are still unclear. Concepts associated with an optimization of FMT such as the "super donor concept" or the "consortia-approach" will be discussed to illustrate open questions and difficulties associated with microbiota therapy in IBD.

The microbiota composition in IBD patients shows significant alterations compared to healthy individuals termed as "dysbiosis". FMT and other therapeutic approaches to modify the microbiota composition have been studied in clinical trials in recent years. Efficacy has been shown in UC; however, many questions with respect to the optimization of microbiota therapy remain to be answered.

Long noncoding RNAs (lncRNAs) play important roles in numerous biological processes, including the immune system. Initial research in this area focused on cell-based studies, but recent advances underscore the profound significance of lncRNAs at the organismal level, providing invaluable insights into their roles in inflammatory diseases. In this rapidly evolving field, lncRNAs have been described with pivotal roles in the intestinal tract where they regulate intestinal homeostasis and inflammation by influencing processes such as immune cell development, inflammatory signaling pathways, epithelial barrier function, and cellular metabolism. Understanding the regulation and function of lncRNAs in this tissue may position lncRNAs not only as potential disease biomarkers but also as promising targets for therapeutic intervention in inflammatory bowel disease and related diseases.

Treatment with anti-tumour necrosis factor α antibodies [anti-TNF] changes the dysbiotic faecal bacteriome in Crohn's disease [CD]. However, it is not known whether these changes are due to decreasing mucosal inflammatory activity or whether similar bacteriome reactions might be observed in gut-healthy subjects. Therefore, we explored changes in the faecal bacteriome and metabolome upon anti-TNF administration [and therapeutic response] in children with CD and contrasted those to anti-TNF-treated children with juvenile idiopathic arthritis [JIA].

Faecal samples collected longitudinally before and during anti-TNF therapy were analysed with regard to the bacteriome by massively parallel sequencing of the 16S rDNA [V4 region] and the faecal metabolome by 1H nuclear magnetic resonance imaging. The response to treatment by mucosal healing was assessed by the MINI index at 3 months after the treatment started. We also tested several representative gut bacterial strains for in vitro growth inhibition by infliximab.

We analysed 530 stool samples from 121 children [CD 54, JIA 18, healthy 49]. Bacterial community composition changed on anti-TNF in CD: three members of the class Clostridia increased on anti-TNF, whereas the class Bacteroidia decreased. Among faecal metabolites, glucose and glycerol increased, whereas isoleucine and uracil decreased. Some of these changes differed by treatment response [mucosal healing] after anti-TNF. No significant changes in the bacteriome or metabolome were noted upon anti-TNF in JIA. Bacterial growth was not affected by infliximab in a disc diffusion test.

Our findings suggest that gut mucosal healing is responsible for the bacteriome and metabolome changes observed in CD, rather than any general effect of anti-TNF.

Cross-talks (e.g., host-driven iron withdrawal and microbial iron uptake between host gastrointestinal tract and commensal microbes) regulate immunotolerance and intestinal homeostasis. However, underlying mechanisms that regulate the cross-talks remain poorly understood. Here, we show that bacterial products up-regulate iron-transporter transferrin and transferrin acts as an immunosuppressor by interacting with cluster of differentiation 14 (CD14) to inhibit pattern recognition receptor (PRR) signaling and induce host immunotolerance. Decreased intestinal transferrin is found in germ-free mice and human patients with ulcerative colitis, which are characterized by impaired intestinal immunotolerance. Intestinal transferrin and host immunotolerance are returned to normal when germ-free mice get normal microbial commensalism, suggesting an association between microbial commensalism, transferrin, and host immunotolerance. Mouse colitis models show that transferrin shortage impairs host's tolerogenic responses, while its supplementation promotes immunotolerance. Designed peptide blocking transferrin-CD14 interaction inhibits immunosuppressive effects of transferrin. In monkeys with idiopathic chronic diarrhea, transferrin shows comparable or even better therapeutic effects than hydrocortisone. Our findings reveal that by up-regulating host transferrin to silence PRR signaling, commensal bacteria counteract immune activation induced by themselves to shape host immunity and contribute for intestinal tolerance.

Diet is thought to contribute to the development of inflammatory bowel disease (IBD) and may act as a mediator of inflammation in patients with IBD. Patients commonly associate their diet with symptoms and inquire about dietary modifications to manage their IBD. Without clinical guidelines and well-established nutritional data, healthcare providers managing patients with IBD may find it difficult to provide recommendations. Strong evidence for enteral nutrition, particularly in the pediatric population, has been established in Crohn's disease (CD) as a therapeutic option. Enteral nutrition may also serve as an adjunct to an exclusion diet. Recent studies such as the randomized trial comparing the Specific Carbohydrate Diet to a Mediterranean Diet in CD patients provide additional insights in forming dietary plans. A low-fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet in quiescent IBD and an anti-inflammatory diet have also been explored as adjunctive therapies. In this review, we discuss the latest evidence for the role of diet in IBD both as a therapeutic modality and as an opportunity to provide patient-centered care.

Dysbiosis is associated with pediatric and adult-onset inflammatory bowel disease (IBD), but the role of dysbiosis and the microbiome in very early onset IBD (VEO-IBD) has not yet been described. Here, we aimed to demonstrate the impact of age and inflammation on microbial community structure using shotgun metagenomic sequencing in children with VEO-IBD, pediatric-onset IBD, and age-matched pediatric healthy controls (HC) observed longitudinally over the course of 8 weeks. We found disease-related differences in alpha and beta diversity between HC and children with IBD or VEO-IBD. Using a healthy microbial maturity index modeled from HC across the age range to characterize their gut microbiota, we found that children with pediatric-onset IBD and VEO-IBD had lower maturity than their age-matched HC groups, suggesting a disease effect on the microbial community. In addition, patients with pediatric IBD had significantly lower maturity than those with VEO-IBD, who had more heterogeneity at the youngest ages, highlighting differences in these two cohorts that were not captured in standard comparisons of alpha and beta diversity. These results demonstrate that young age and inflammation independently impact microbial community structure. However, the effect is not additive in the youngest patients, likely because of the heterogeneous and dynamic stool microbiome in this population.

Gut microbiota is an indispensable commensal partner of human superorganism. The wealth of genetic repertoire provided by these microorganisms extends host's substrate processing capability. Energy and nutrient harvesting machinery primarily depends on the proper function of these organisms. However, the dynamic composition of microbiota changes with age, lifestyle, stress factors, infections, medications, and host pathophysiological conditions. Host immune system is primarily responsible for shaping up the microbial community and sustaining the symbiotic state. This involves controlling the delicate balance between agility toward pathobionts and tolerance toward symbionts. When things go wrong with this crosstalk, dysbiosis may arise.Metabolic syndrome is a multisystemic, low-grade chronic inflammatory disease that involves dyslipidemia, glucose intolerance, insulin resistance, and central obesity. Excess caloric intake with high-sugar and high-fat diet promote high energy harvesting and lipogenesis. The secretion of adipokines accompanies lipid spillover from fat cells, which contribute to insulin resistance and the expansion of adipose tissue in ectopic sites. Proinflammatory cytokines from adipose tissue macrophages increase the extent of adipose dysfunction.The inflammatory nature of obesity and metabolic syndrome recall the connection between dysbiosis and immune dysfunction. A remarkable association exits between obesity, inflammatory bowel disease, gluten-sensitive enteropathy, and dysbiosis. These conditions compromise the gut mucosa barrier and allow lipopolysaccharide to enter circulation. Unresolved chronic inflammation caused by one condition may overlap or trigger the other(s). Experimental studies and therapeutic trials of fecal microbiota transplantation promise limited improvement in some of these conditions.Typically, metabolic syndrome is considered as a consequence of overnutrition and the vicious cycle of lipogenesis, lipid accumulation, and chronic low-level inflammation. Because of the complex nature of this disorder, it remains inconclusive whether dysbiosis is a cause or consequence of obesity and metabolic syndrome.

With new advances in next generation sequencing (NGS) technology at reduced costs, research on bacterial genomes in the environment has become affordable. Compared to traditional methods, NGS provides high-throughput sequencing reads and the ability to identify many species in the microbiome that were previously unknown. Numerous bioinformatics tools and algorithms have been developed to conduct such analyses. However, in order to obtain biologically meaningful results, the researcher must select the proper tools and combine them to construct an efficient pipeline. This complex procedure may include tens of tools, each of which require correct parameter settings. Furthermore, an NGS data analysis involves multiple series of command-line tools and requires extensive computational resources, which imposes a high barrier for biologists and clinicians to conduct NGS analysis and even interpret their own data. Therefore, we established a public gut microbiome database, which we call Twnbiome, created using healthy subjects from Taiwan, with the goal of enabling microbiota research for the Taiwanese population. Twnbiome provides users with a baseline gut microbiome panel from a healthy Taiwanese cohort, which can be utilized as a reference for conducting case-control studies for a variety of diseases. It is an interactive, informative, and user-friendly database. Twnbiome additionally offers an analysis pipeline, where users can upload their data and download analyzed results. Twnbiome offers an online database which non-bioinformatics users such as clinicians and doctors can not only utilize to access a control set of data, but also analyze raw data with a few easy clicks. All results are customizable with ready-made plots and easily downloadable tables. Database URL: http://twnbiome.cgm.ntu.edu.tw/ .

Inflammatory bowel disease (IBD) is becoming more common in the Western world due to changes in diet-related microbial dysbiosis, genetics and lifestyle. Incidences of gut permeability can predate IBD and continued gut barrier disruptions increase the exposure of bacterial antigens to the immune system thereby perpetuating chronic inflammation. Currently, most of the approved IBD therapies target individual pro-inflammatory cytokines and pathways. However, they fail in approximately 50% of patients due to their inability to overcome the redundant pro inflammatory immune responses. There is increasing interest in the therapeutic potential of T regulatory cells (Tregs) in inflammatory conditions due to their widespread capability to dampen inflammation, promote tolerance of intestinal bacteria, facilitate healing of the mucosal barrier and ability to be engineered for more targeted therapy. Intestinal Treg populations are inherently shaped by dietary molecules and gut microbiota-derived metabolites. Thus, understanding how these molecules influence Treg-mediated preservation of the intestinal barrier will provide insights into immune tolerance-mediated mucosal homeostasis. This review comprehensively explores the interplay between diet, gut microbiota, and immune system in influencing the intestinal barrier function to attenuate the progression of colitis.

Diverticular disease (DD) is a common condition in Western countries. The role of microbiota in the pathogenesis of DD and its related symptoms has been frequently postulated since most complications of this disease are bacteria-driven and most therapies rely on microbiota modulation. Preliminary data showed fecal microbial imbalance in patients with DD, particularly when symptomatic, with an increase of pro-inflammatory and potentially pathogenetic bacteria. In addition, bacterial metabolic markers can mirror specific pathways of the disease and may be even used for monitoring treatment effects. All treatments currently suggested for DD can affect microbiota structure and metabolome compositions.

Sparse evidence is available linking gut microbiota perturbations, diverticular disease pathophysiology, and symptom development. We aimed to summarize the available knowledge on gut microbiota evaluation in diverticular disease, with a focus on symptomatic uncomplicated DD, and the relative treatment strategies.

Ulcerative colitis (UC) is an immune-mediated inflammation of the colonic mucosa. Gut microbiota dysbiosis may play a significant role in disease pathogenesis by causing shifts in metabolomic profiles within the gut. To identify differences and trends in the metabolomic profile of paediatric UC patients pre- and post-faecal microbiota transplants (FMT). Forty-six paediatric patients with mild-to-moderate UC and 30 healthy paediatric patients were enrolled in this study. Baseline stool samples were collected prior to FMT initiation and at months 1, 3, 6, and 12 post-FMT. Pediatric Ulcerative Colitis Activity Index (PUCAI) scores were calculated at baseline and months 1, 3, 6, and 12 after FMT. The average Bray-Curtis dissimilarities to healthy subjects decreased after FMT. In principal coordinate analysis plots, UC patients' centroids drew nearer to healthy individuals. The variance explained by phenotype (Healthy versus UC) reduced and remained significant. From 1 to 3 months after FMT, PUCAI trends were statistically significant and decreasing. PUCAI scores remain flat starting 6 months after FMT. This study concludes that paediatric UC patients have a significantly different baseline metabolite profile than healthy controls. Although being time limited, FMT significantly altered these metabolite profiles and shifted them towards that of healthy controls.

The impact of chronic low-grade inflammation in the development of non-alcoholic fatty liver disease (NAFLD) has been studied widely. Previous studies showed gut pathogens' effects on inflammation development in NAFLD patients; hence, hypothetically, gut microbial therapy by administration of probiotics, synbiotics, and prebiotics may alleviate inflammation in these individuals. Several studies were performed in this regard; however, conflicting results were obtained. In this study, we aimed to comprehensively evaluate the effects of gut microbial therapy on inflammatory markers in NAFLD patients in a meta-umbrella design.

Two independent researchers investigated international databases, including PubMed, Web of Science, Scopus, and Cochrane Library, from inception until March 2023. Meta-analyses evaluating the impact of probiotics, synbiotics, or prebiotics on inflammatory markers of patients with NAFLD were eligible for our study. AMASTAR 2 checklist was used to evaluate the quality of included studies. Random effect model was performed for the analysis, and Egger's regression test was conducted to determine publication bias.

A total number of 12 studies were entered into our analysis. Our findings revealed that gut microbial therapy could significantly reduce serum C-reactive protein (CRP) levels among NAFLD patients (ES: -0.58; 95% CI: -0.73, -0.44, P < 0.001). In subgroup analysis, this reduction was observed with both probiotics (ES: -0.63; 95% CI: -0.81, -0.45, P < 0.001) and synbiotics (ES: -0.49; 95% CI: -0.74, -0.24, P < 0.001). In addition, gut microbial therapy could significantly decrease tumor necrosis factor-a (TNF-a) levels in NAFLD patients (ES: -0.48; 95% CI: -0.67 to -0.30, P < 0.001). In subgroup analysis, this decrease was observed with probiotics (ES: -0.32; 95% CI: -0.53, -0.11, P = 0.002) and synbiotics (ES: -0.96; 95% CI: -1.32, -0.60, P < 0.001). Not enough information was available for assessing prebiotics' impacts.

The results of this umbrella review suggest that probiotics and synbiotics have promising effects on inflammatory markers, including TNF-a and CRP; however, more research is needed regarding the effects of prebiotics.

CRD42022346998.

The gut microbiome has been increasingly recognized as a key player in the development and progression of colon cancer. Alterations in the gut microbiota, known as dysbiosis, can lead to a variety of medical issues. Microbial adaptation through signals and small molecules can enhance pathogen colonization and modulate host immunity, significantly impacting disease progression. Quorum sensing peptides and molecules have been linked to the progression of colon cancer. Various interventions, such as fecal microbiota transplantation, probiotics, prebiotics, synbiotics, and antibiotics, have been used to reverse dysbiosis with mixed results and potential side effects. Thus, a personalized approach to treatment selection based on patient characteristics, such as individual gut microbiota manipulation, is necessary to prevent and treat diseases like colon cancer. With advances in metagenomic sequencing and other omics technologies, there has been a growing interest in developing precision medicine strategies for microbial imbalance-induced colon cancer. This review serves as a comprehensive synthesis of current knowledge on the gut microbiome involvement in colon cancer. By exploring the potential of utilizing the gut microbiome as a target for precision medicine, this review underscores the exciting opportunities that lie ahead. Although challenges exist, the integration of microbiome data into precision medicine approaches has the potential to revolutionize the management of colon cancer, providing patients with more personalized and effective treatment options.

This review examines the current literature on the gut-skin connection in alopecia and summarizes interventions that impact hair growth by modulation of the gut or skin microbiome.

PubMed searches were done to assess studies of the gut and skin microbiome and forms of alopecia including, alopecia areata (AA), androgenic alopecia (AGA), alopecia universalis (AU), central centrifugal cicatricial alopecia (CCCA) and lichen planopilaris (LPP). Filters were applied for human and animal studies. Articles not translated to English and studies assessing supplemental therapies on alopecia were excluded.

There is evidence that scalp, hair follicle, and gut microbiome alterations are associated with various types of alopecia. There is potential in the use of interventions targeting microbiome dysbiosis, including fecal transplants and probiotics.

This field of study still requires more high-quality research and studies with larger participant populations.

Dysbiosis on the scalp, within the hair follicle and the gut seem to have a role in the pathophysiology of various forms of alopecia. There is evidence that interventions targeting dysbiosis may have potential in the treatment and management of hair loss. Further studies are needed to establish a direct connection and to clarify specific effects of these interventions.

Lung cancer is the leading cause of cancer-related deaths worldwide. Tobacco smoking and air pollution are believed to be responsible for more than 90% of lung cancers. Respiratory pathogens are also known to be associated with the initiation and development of lung cancer. Despite the fact that the bacterial biomass in the lungs is lower than that in the intestinal tract, emerging evidence indicates that the lung is colonized by a diverse array of microbes. However, there is limited knowledge regarding the role of dysbiosis of the lung microbiota in the progression of lung cancer. In this review, we summarize the current information about the relationship between the microbiome and lung cancer. The objective is to provide an overview of the core composition of the microbiota in lung cancer as well as the role of specific dysbiosis of the lung microbiota in the progression of lung cancer and treatment of the disease.

Changes in diet and environment can lead to acute diarrhea in companion animals, but the composition and interactions of the gut microbiome during acute diarrhea remain unclear. In this multicenter case-control study, we investigated the relationship between intestinal flora and acute diarrhea in two breeds of cats. Acutely diarrheic American Shorthair (MD, n = 12) and British Shorthair (BD, n = 12) and healthy American Shorthair (MH, n = 12) and British Shorthair (BH, n = 12) cats were recruited. Gut microbial 16S rRNA sequencing, metagenomic sequencing, and untargeted metabolomic analysis were performed. We observed significant differences in beta-diversity (Adonis, P < 0.05) across breeds and disease state cohorts. Profound differences in gut microbial structure and function were found between the two cat breeds. In comparison to healthy British Shorthair cats, Prevotella, Providencia, and Sutterella were enriched while Blautia, Peptoclostridium, and Tyzzerella were reduced in American Shorthair cats. In the case-control cohort, cats with acute diarrhea exhibited an increased abundance of Bacteroidota, Prevotella, and Prevotella copri and a decreased abundance of Bacilli, Erysipelotrichales, and Erysipelatoclostridiaceae (both MD and BD cats, P < 0.05). Metabolomic analysis identified significant changes in the BD intestine, affecting 45 metabolic pathways. Moreover, using a random forest classifier, we successfully predicted the occurrence of acute diarrhea with an area under the curve of 0.95. Our findings indicate a distinct gut microbiome profile that is associated with the presence of acute diarrhea in cats. However, further investigations using larger cohorts of cats with diverse conditions are required to validate and extend these findings. IMPORTANCE Acute diarrhea is common in cats, and our understanding of the gut microbiome variations across breeds and disease states remains unclear. We investigated the gut microbiome of two cat breeds (British Shorthair and American Shorthair) with acute diarrhea. Our study revealed significant effects of breeds and disease states on the structure and function of the gut microbiota in cats. These findings emphasize the need to consider breed-related factors in animal nutrition and research models. Additionally, we observed an altered gut metabolome in cats with acute diarrhea, closely linked to changes in bacterial genera. We identified a panel of microbial biomarkers with high diagnostic accuracy for feline acute diarrhea. These findings provide novel insights into the diagnosis, classification, and treatment of feline gastrointestinal diseases.

Intestinal epithelial cells (IECs) perform several physiological and metabolic functions at the epithelial barrier. IECs also play an important role in defining the overall immune functions at the mucosal region. Pattern recognition receptors (PRRs) on the cell surface and in other cellular compartments enable them to sense the presence of microbes and microbial products in the intestinal lumen. IECs are thus at the crossroads of mediating a bidirectional interaction between the microbial population and the immune cells present at the intestinal mucosa. This communication between the microbial population, the IECs and the underlying immune cells has a profound impact on the overall health of the host. In this review, we focus on the various PRRs present in different cellular compartments of IECs and discuss the recent developments in the understanding of their role in microbial recognition. Microbial recognition and signaling at the epithelial barrier have implications in the maintenance of intestinal homeostasis, epithelial barrier function, maintenance of commensals, and the overall tolerogenic function of PRRs in the gut mucosa. We also highlight the role of an aberrant microbial sensing at the epithelial barrier in the pathogenesis of inflammatory bowel disease (IBD) and the development of colorectal cancer.

Inflammatory bowel disease (IBD) is an illness with increasing prevalence, particularly in emerging countries, which can have a substantial impact on the quality of life of the patient. The illness is rather heterogeneous with different evolution among patients. A machine learning approach is followed in this paper to identify potential genes that are related to IBD. This is done by following a Monte Carlo simulation approach. In total, 23 different machine learning techniques were tested (in addition to a base level obtained using artificial neural networks). The best model identified 74 genes selected by the algorithm as being potentially involved in IBD. IBD seems to be a polygenic illness, in which environmental factors might play an important role. Following a machine learning approach, it was possible to obtain a classification accuracy of 84.2% differentiating between patients with IBD and control cases in a large cohort of 2490 total cases. The sensitivity and specificity of the model were 82.6% and 84.4%, respectively. It was also possible to distinguish between the two main types of IBD: (1) Crohn's disease and (2) ulcerative colitis.

Hepatic liver disease, including primary sclerosing cholangitis (PSC), is a serious extraintestinal manifestations of colonic inflammation. Cyclic adenosine monophosphate (cAMP)-responsive element-binding protein H (CrebH) is a transcription factor expressed mostly in the liver and small intestine. However, CrebH's roles in the gut-liver axis remain unknown.

Inflammatory bowel disease (IBD) and PSC disease models were established in wild-type and CrebH^-/- mice treated with dextran sulfate sodium, dinitrobenzene sulfonic acid, and diethoxycarbonyl dihydrocollidine diet, respectively. RNA sequencing were conducted to investigate differential gene expression. Exosomes were isolated from plasma and culture media. miRNA expression profiling was performed using the NanoString nCounter Mouse miRNA Panel. Effects of miR-29a-3p on adhesion molecule expression were investigated in bEnd.3 brain endothelial cells.

CrebH^-/- mice exhibited accelerated liver injury without substantial differences in the gut after administration of dextran sulfate sodium (DSS), and had similar features to PSC, including enlarged bile ducts, enhanced inflammation, and aberrant MAdCAM-1 expression. Furthermore, RNA-sequencing analysis showed that differentially expressed genes in the liver of CrebH^-/- mice after DSS overlapped significantly with genes changed in PSC-liver. Analysis of plasma exosome miRNA isolated from WT and CrebH^-/- mice indicates that CrebH can contribute to the exosomal miRNA profile. We also identified miR-29a-3p as an effective mediator for MAdCAM-1 expression. Administration of plasma exosome from CrebH^-/- mice led to prominent inflammatory signals in the liver of WT mice with inflammatory bowel disease (IBD).

CrebH deficiency led to increased susceptibility to IBD-induced liver diseases via enhanced expression of adhesion molecules and concomitant infiltration of T lymphocytes. Exosomes can contribute to the progression of IBD-induced liver injury in CrebH^-/- mice. These study provide novel insights into the role of CrebH in IBD-induced liver injury.