Chronic infection with Toxoplasma gondii (T. gondii) results in severe damages to the integrity of intestinal barrier, however, both the underlying mechanism and feasible intervention strategies are still little known. Here, we found that both the chronic infection of T. gondii and transplanting gut microbiota from T. gondii-infected mice severely impaired the mice intestinal integrity, which was characterized by significantly decreased thickness of inner mucus layer and down-regulated expression of three tight junction proteins Occludin, ZO-1, and Claudin (p < 0.05). Moreover, T. gondii infection also led to mice intestinal microbiota dysbiosis, especially butyrate-producing bacteria, and significantly changed the expression of several senescence-associated markers, including 6- and 7- fold upregulation for P16, P21, and 6-fold downregulation for Lamin B1 at mRNA levels, and 2-fold downregulation for β-galactosidase at protein levels (p < 0.05). Interestingly, subsequent administration with dietary butyrate could alleviate T. gondii-induced intestinal integrity impairment and cell senescence, revealing a significant increase of the inner mucus layer thickness (p < 0.001), and a remarkable decrease in P16, P21, β-galactosidase expression levels while an upregulation of Lamin B1 expression (p < 0.05). Taken together, our study revealed that T. gondii-induced dysbiosis of gut microbiota, especially butyrate-producing bacteria, contributes to the intestinal impairment, potentially via promoting cell senescence. In addition, administration with the metabolite, butyrate, could be a promising therapeutic measure against T. gondii infection.

Clostridioides difficile infection (CDI) frequently occurs concurrently in patients with inflammatory bowel disease (IBD), and differential diagnosis from IBD flares is critical. However, clinical management of C. difficile in IBD patients with polymerase chain reaction toxin-positive (tPCR+)/enzyme immunoassay toxin-negative (tEIA-) results has not yet been investigated.

We aimed to assess the clinical significance of C. difficile tPCR+/tEIA- in patients with IBD and the impact of antibiotic treatment on IBD outcomes.

This single-center, retrospective cohort study included patients with IBD with CDI test results between January 01, 2018, and August 01, 2022. First, the clinical outcomes of IBD, such as medication escalation, hospitalization, and surgery, were compared between patients with IBD with tPCR-/tEIA- and those with tPCR+/tEIA- using Cox regression and propensity score matching. Next, the clinical outcomes of IBD were assessed based on whether antibiotic treatment for CDI was administered to both groups.

Among 412 patients with IBD with PCR test, 71 (17.2%) showed tPCR+/tEIA- results. The tPCR+/tEIA- group showed no statistically significant difference in IBD outcomes compared to the tPCR-/tEIA- group. The antibiotic-treated tPCR+/tEIA- group showed a higher risk of drug escalation and admission than the tPCR-/tEIA- group, while the antibiotic-untreated tPCR+/tEIA- group did not. After drug escalation during the follow-up, the treated tPCR+/tEIA- group showed IBD outcomes similar to those of the tPCR-/tEIA- group.

In patients with IBD with indeterminate CDI, the need for antibiotics should be thoroughly assessed and proper management of underlying IBD such as drug escalation may lead to favorable outcomes.

Wastewater treatment plant (WWTP) workers are exposed to bioaerosols containing bacteria, fungi, and endotoxin, potentially posing health risks to workers. This study quantified personal exposure levels to airborne bacteria and fungi, endotoxin, and dust among 44 workers during two seasons at four WWTPs. Associations between the exposure measurements and serum levels of biomarkers CRP, SAA, and CC16 were also assessed. The potential deposition of viable microorganisms in workers' airways were explored using stationary fractionating samplers. Microbial communities were characterized using long-read nanopore amplicon sequencing and MALDI-TOF mass spectrometry to identify species, including pathogenic or allergenic microorganisms. We found that bacterial and fungal exposure levels were significantly associated with work task (p < 0.001 and p = 0.00041, respectively), with high exposure variability within and between tasks. Workshop, sewer system inspection, and sewer cleaning were associated with the highest exposure levels. A significant positive correlation was found between CRP and bacterial exposure (p = 0.013), while significant negative correlations were found between CRP and endotoxin and dust exposures (p = 0.012 and p = 0.018, respectively). No significant associations were found between SAA or CC16 and the exposure measures. Microbial community composition in bioaerosols differed significantly between some work tasks while others showed similar compositions. Viable hazardous microorganisms such as Clostridium perfringens and Aspergillus fumigatus were found in workers' exposures and in respiratory fractions of stationary air samples, indicating potential lung deposition. Further research is needed to assess possible long-term health risks from bioaerosol exposure at WWTPs.

Background/Objectives: There is a limited body of evidence regarding dietary intake in children with inflammatory bowel disease despite increasing research about the nutritional implications in the disease pathogenesis. Functional abdominal pain disorders (FAPDs) are also chronic disorders marked by chronic abdominal pain, currently described with the ROME IV criteria. This study was aimed to investigate the adherence to healthy eating habits in an inflammatory bowel disease pediatric population when compared to a matched population with functional abdominal pain gastrointestinal disorders. Methods: We performed a single centre study focused on dietary patterns in children with IBD and FAPDs between January 2021 and April 2024. Data collected included general information, disease phenotype, and the KIDMED index regarding healthy eating. Results: The final analysis was based on full data from the KIDMED index available for 122 (57 vs. 65) participants. Overall, the average KIDMED score did not vary significantly between the study population, meaning 6.89 ± 2.33 for the IBD group and 7.11 ± 2.67 for FAPDs group, p = 0.34. In the same KIDMED index group, mean values were higher for FAPDs patients, but results differ statistically significant only for "medium" adherence to healthy diet, showing that larger proportion of IBD patients were previously exposed to non-healthy diets: 8.99 vs. 11.1, p = 0.45, 5.02 vs. 6.92, p = 0.05, 2.89 vs. 2.56, p = 0.43, for group 1, 2, and 3, respectively. Conclusions: This study showed in our cohort that overall adherence to a healthy pattern diet is poor prior to diagnosis of different gastrointestinal pathologies in children.

Several studies have highlighted alteration in the gut microbiome associated with the onset and progression of diseases. Recognizing the potential of gut microbiota as biomarkers, this systematic review seeks to synthesize current data on the intricate relationship between the host gut microbiome profiles and their usefulness for the development of diagnostic, prognostic and therapeutic approaches to control human schistosomiasis.

A systematic literature review was carried out by searching for relevant studies published until date, that is May 2024, using Medline, Embase, Global Health, Web of Science, and Global Index Medicus databases. The keywords used to select articles were "Gut microbiome", "Gut Microbiota", "Schistosomiasis", "Bilharziasis ", and "Human". Extracted data were analysed qualitatively from the selected articles.

Of the 885 articles retrieved and screened, only 13 (1.47%) met the inclusion criteria and were included in this review. Of the included studies, 6 (46.2%) explored alterations of gut microbiome in schistosome-infected patients, 4 (30.7%) in patients with liver pathologies, and 3 (23.1%) in patients treated with praziquantel. Bacteria from the genera Bacteroides, Faecalibacterium, Blautia and Megasphaera were associated with S. japonicum and S. haematobium infection in school-aged children, whereas infection with S. mansoni rather associated with Klebsiella and Enterobacter. The gut microbiota signature in patient with schistosomiasis-induced liver pathology was reported only for S. japonicum, and the genus Prevotella appeared as a non-invasive biomarker of S. japonicum-associated liver fibrosis. For S. mansoni-infected school-aged children, it further appeared that the treatment outcome following praziquantel administration associated with the abundance in the gut microbiome of bacteria from the classes Fusobacteriales, Rickettsiales and Neisseriales.

The host gut microbiome appears to be a valuable, non-invasive, but still poorly utilized, source of host biomarkers potentially informative for better diagnosing, prognosing and treating schistosomiasis. Further studies are therefore needed to comprehensively define such gut microbial biomarkers of human schistosomiasis and catalyse the informed development of gut microbiome-based tools of schistosomiasis control.

The gut barrier is the first line of defense against harmful substances and pathogens in the intestinal tract. The balance of proliferation and apoptosis of intestinal epithelial cells (IECs) is crucial for maintaining the integrity of the intestinal mucosa and its function. However, oxidative stress and inflammation can cause DNA damage and abnormal apoptosis of the IECs, leading to the disruption of the intestinal epithelial barrier. This, in turn, can directly or indirectly cause various acute and chronic intestinal diseases. In recent years, there has been a growing understanding of the vital role of dietary ingredients in gut health. Studies have shown that certain amino acids, fibers, vitamins, and polyphenols in the diet can protect IECs from excessive apoptosis caused by oxidative stress, and limit intestinal inflammation. This review aims to describe the molecular mechanism of apoptosis and its relationship with intestinal function, and to discuss the modulation of IECs' physiological function, the intestinal epithelial barrier, and gut health by various nutrients. The findings of this review may provide a theoretical basis for the use of nutritional interventions in clinical intestinal disease research and animal production, ultimately leading to improved human and animal intestinal health.

The concept of using diet as therapy in inflammatory bowel disease is of interest to clinicians and patients. Once considered to play a minor role, diet is now known to not only affect disease onset but may also serve as a therapeutic tool for inducing and maintaining remission and improving surgical outcomes. Further research is needed to fully elucidate how, when, and in whom diet therapies may be best applied to improve clinical and disease outcomes. The aim of this review was to summarize current research findings and serve as a tool to help facilitate patient-clinician conversations.

Bacteroides fragilis (B. fragilis) is a Gram-negative, obligate anaerobic, commensal bacterium residing in the human gut and holds therapeutic potential for ulcerative colitis (UC). Previous studies have indicated that capsular polysaccharide A (PSA) of B. fragilis is a crucial component for its effectiveness, possessing various biological activities such as anti-inflammatory, anti-tumor, and immune-modulating effects. We previously isolated and characterized the B. fragilis strain ZY-312 from the feces of a healthy breastfed infant, and extracted its PSA, named TP2. In this study, we explored the impact of TP2 on colonic inflammation and delved into its potential mechanisms. Initially, we used 2,4,6-trinitrobenzenesulfonic acid (TNBS) to induce colitis in rats and found that TP2 treatment significantly ameliorated TNBS-induced weight loss, increased clinical scores, extensive ulcers, and intestinal epithelial damage in UC rats. Further analysis revealed that TP2 effectively restored the intestinal barrier integrity in UC rats by regulating the expression of Muc-2, tight junction proteins (ZO-1, occludin, claudin-1, and claudin-2), as well as apoptosis-related proteins Bcl-2, BAX, and Cleaved-Caspase-3. Additionally, TP2 suppressed the expression of pro-inflammatory cytokines TNF-α, IL-1β, IL-6, and IL23, while promoting the secretion of anti-inflammatory cytokines IL-10 and IL-22, thereby inhibiting the occurrence of inflammation. TP2 also downregulated the phosphorylation levels of AKT and PI3K, effectively inhibiting the abnormal activation of the PI3K/AKT signaling pathway. More interestingly, 16S rRNA sequencing results showed that TP2 restored the ecological imbalance of the rat intestinal microbiota, with an increase in beneficial bacteria such as Lactobacillus and Limosilactobacillus observed in the treatment group. In conclusion, TP2 through the regulation of intestinal barrier-related cells and proteins, inhibition of apoptosis, modulation of inflammation-related cytokine levels, and control of abnormal activation of the PI3K/AKT signaling pathway, restores intestinal barrier integrity. Additionally, by reshaping the ecological imbalance of the gut microbiota, TP2 ultimately alleviates ulcerative colitis in rats.

Gut microbiota plays a prominent role in regulation of host nutrientmetabolism, drug and xenobiotics metabolism, immunomodulation and defense against pathogens. It synthesizes numerous metabolites thatmaintain the homeostasis of host. Any disbalance in the normalmicrobiota of gut can lead to pathological conditions includinginflammation and tumorigenesis. In the past few decades, theimportance of gut microbiota and its implication in various diseases, including cancer has been a prime focus in the field of research. Itplays a dual role in tumorigenesis, where it can accelerate as wellas inhibit the process. Various evidences validate the effects of gutmicrobiota in development and progression of malignancies, wheremanipulation of gut microbiota by probiotics, prebiotics, dietarymodifications and faecal microbiota transfer play a significant role.In this review, we focus on the current understanding of theinterrelationship between gut microbiota, immune system and cancer,the mechanisms by which they play dual role in promotion andinhibition of tumorigenesis. We have also discussed the role ofcertain bacteria with probiotic characteristics which can be used tomodulate the outcome of the various anti-cancer therapies under theinfluence of the alteration in the composition of gut microbiota.Future research primarily focusing on the microbiota as a communitywhich affect and modulate the treatment for cancer would benoteworthy in the field of oncology. This necessitates acomprehensive knowledge of the roles of individual as well asconsortium of microbiota in relation to physiology and response ofthe host.

Imbalances in Th1/Th2 and Th17/Treg immune axes, coupled with disruptions in the gut microbiota (GM), play a pivotal role in the pathogenesis of inflammatory bowel disease (IBD). Cordycepin, a natural anti-inflammatory compound, holds promise in mitigating IBD by rebalancing these immune axes in conjunction with modulating the GM. The aim of this experiment is to investigate the potential of cordycepin in mitigating enteritis and elucidate the underlying mechanisms associated with its ameliorative effects on enteritis.

On the day of inducing experimental colitis with Dextran Sulfate Sodium (DSS), mice in the DSS + Cordycepin and Cordycepin groups received 50 mg/kg/day Cordycepin via intra-gastric administration (i.g.) for seven consecutive days, respectively. Mice in the DSS and control groups were treated with equal volumes of saline. On day 8, all mice were euthanized under pentobarbital sodium anesthesia.

In a DSS-induced colitis mouse model, Cordycepin treatment led to a significant reduction in the disease activity index (DAI), splenic weight, and colonic pathological injury while simultaneously improving body weight and colonic length. Furthermore, it positively impacted GM composition, resulting in decreased Th1 and Th17 cells, alongside an increase in Th2 and Treg cells. The contents of the mouse colon were extracted for microbial community analysis. Mouse blood was prepared into a single-cell suspension, and flow cytometry was used to assess the expressio of Treg, Th17, Th1, and Th2 immune cells.

These results underscored the effective intervention of cordycepin in ameliorating DSS-induced colitis by harmonizing the interplay between GM and immune homeostasis.

Crohn's Disease (CD) is characterized by chronic intestinal inflammation and dysbiosis. This study aimed to investigate the effects of a plant-based diet (PBD) on gut microbiota composition and inflammation in CD patients and assess the utility of trnL gene sequencing for monitoring dietary adherence.

Fourteen CD patients participated in a 12-week PBD intervention. Dietary adherence was monitored through self-reported food diaries and trnL sequencing, which detects plant residues in fecal samples. Gut microbiota was analyzed using 16S rRNA sequencing, and fecal calprotectin levels were measured as an indicator of intestinal inflammation.

TrnL sequencing identified 55 plant genera in fecal samples, compared to 41 reported in food diaries, highlighting its accuracy in assessing plant residue diversity. By week 4, participants demonstrated a 1.4-fold increase in plant intake, correlating with a significant increase in microbial diversity. Key genera associated with gut health, such as Faecalibacterium and Bacteroides, increased in abundance. Additionally, fecal calprotectin levels decreased from 472 mg/kg at baseline to 207 mg/kg at week 12, indicating reduced intestinal inflammation.

A PBD positively influenced gut microbiota composition and decreased intestinal inflammation in CD patients. The study also demonstrated that trnL sequencing is an effective tool for assessing dietary adherence in clinical settings, offering a more objective measure than self-reported food diaries.

This review provides a comprehensive overview of the current state of probiotic research, covering a wide range of topics, including strain identification, functional characterization, preclinical and clinical evaluations, mechanisms of action, therapeutic applications, manufacturing considerations, and future directions. The screening process for potential probiotics involves phenotypic and genomic analysis to identify strains with health-promoting properties while excluding those with any factor that could be harmful to the host. In vitro assays for evaluating probiotic traits such as acid tolerance, bile metabolism, adhesion properties, and antimicrobial effects are described. The review highlights promising findings from in vivo studies on probiotic mitigation of inflammatory bowel diseases, chemotherapy-induced mucositis, dysbiosis, obesity, diabetes, and bone health, primarily through immunomodulation and modulation of the local microbiota in human and animal models. Clinical studies demonstrating beneficial modulation of metabolic diseases and human central nervous system function are also presented. Manufacturing processes significantly impact the growth, viability, and properties of probiotics, and the composition of the product matrix and supplementation with prebiotics or other strains can modify their effects. The lack of regulatory oversight raises concerns about the quality, safety, and labeling accuracy of commercial probiotics, particularly for vulnerable populations. Advancements in multi-omics approaches, especially probiogenomics, will provide a deeper understanding of the mechanisms behind probiotic functionality, allowing for personalized and targeted probiotic therapies. However, it is crucial to simultaneously focus on improving manufacturing practices, implementing quality control standards, and establishing regulatory oversight to ensure the safety and efficacy of probiotic products in the face of increasing therapeutic applications.

It is believed that gut microbiota alteration leads to both intestinal and non-intestinal diseases in children. Since infants inherit maternal microbiota during pregnancy and lactation, recent studies suggest that changes in maternal microbiota can cause immune disorders as well. This systematic review was designed to assess the association between the child and mother's gut microbiome and allergy development in childhood.

In this systematic review, international databases including PubMed, Scopus, and ISI/WOS were searched until January 2023 to identify relevant studies.

Observational studies that analyzed infant or maternal stool microbiome and their association with allergy development in children were included in this study. Data extraction and quality assessment of the included studies were independently conducted by two researchers.

Of the 1694 papers evaluated, 21 studies examined neonate gut microbiome by analyzing stool samples and six studies examined maternal gut microbiota. A total of 5319 participants were included in this study. Asthma followed by eczema and dermatitis were the most common allergy disorders among children. Urbanization caused a lack of diversity in the bacterial microbiota as well as lower levels of Bifidobacterium and Lachnospira associated with a higher risk of allergy. In contrast, higher levels of Roseburia and Flavonifractor were associated with lower allergy risk.

This systematic review shows that gut microbiota may be associated with allergy development. Further studies are required to provide a definitive answer.

The importance of diet in shaping the gut microbiota is well established and may help improve an individual's overall health. Many other factors, such as genetics, age, exercise, antibiotic therapy, or tobacco use, also play a role in influencing gut microbiota.

This narrative review summarizes how three distinct dietary types (plant-based, Mediterranean, and Western) affect the composition of gut microbiota and the development of non-communicable diseases (NCDs).

A comprehensive literature search was conducted using the PubMed, Web of Science, and Scopus databases, focusing on the keywords "dietary pattern", "gut microbiota" and "dysbiosis".

Both plant-based and Mediterranean diets have been shown to promote the production of beneficial bacterial metabolites, such as short-chain fatty acids (SCFAs), while simultaneously lowering concentrations of trimethylamine-N-oxide (TMAO), a molecule associated with negative health outcomes. Additionally, they have a positive impact on microbial diversity and therefore are generally considered healthy dietary types. On the other hand, the Western diet is a typical example of an unhealthy nutritional approach leading to an overgrowth of pathogenic bacteria, where TMAO levels rise and SCFA production drops due to gut dysbiosis.

The current scientific literature consistently highlights the superiority of plant-based and Mediterranean dietary types over the Western diet in promoting gut health and preventing NCDs. Understanding the influence of diet on gut microbiota modulation may pave the way for novel therapeutic strategies.

Inflammatory Bowel Disease (IBD) is an enduring inflammatory disease of the gastrointestinal tract (GIT). The complexity of IBD, its profound impact on patient's quality of life, and its burden on healthcare systems necessitate continuing studies to elucidate its etiology, refine care strategies, improve treatment outcomes, and identify potential targets for novel therapeutic interventions. The discovery of a connection between IBD and gut bacterial quorum sensing (QS) molecules has opened exciting opportunities for research into IBD pathophysiology. QS molecules are small chemical messengers synthesized and released by bacteria based on population density. These chemicals are sensed not only by the microbial species but also by host cells and are essential in gut homeostasis. QS molecules are now known to interact with inflammatory pathways, therefore rendering them potential therapeutic targets for IBD management. Given these intriguing developments, the most recent research findings in this area are herein reviewed. First, the global burden of IBD and the disruptions of the gut microbiota and intestinal barrier associated with the disease are assessed. Next, the general QS mechanism and signaling molecules in the gut are discussed. Then, the roles of QS molecules and their connection with IBD are elucidated. Lastly, the review proposes potential QS-based therapeutic targets for IBD, offering insights into the future research trajectory in this field.

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.

Literature on dietary behaviours of the pediatric Crohn's Disease (CD) population and the relationship between dietary intake and CD activity is limited. Three dietary indices were developed and tested to conduct dietary pattern analysis in pediatric patients with CD consuming a free diet following remission induction via exclusive enteral nutrition (n = 11). Index scores underwent descriptive and inferential analysis. The mean adjusted scores (out of 100) for the Pediatric Western Diet Index, Pediatric Prudent Diet Index, and Pediatric-Adapted 2010 Alternate Healthy Eating Index (PA2010-AHEI) were 29.82 ± 15.22, 34.25 ± 15.18, and 51.50 ± 11.69, respectively. The mean Western-to-Prudent ratio was 0.94 ± 0.55. A significant correlation (r = -0.71) and relationship (F[1, 9] = 9.04, P < 0.05, R2 = 0.501) between the Western-to-Prudent ratio and PA2010-AHEI was found. The results suggest participants were not following a Western or Prudent diet, and were consuming foods not captured by the indices. More research is needed to describe dietary intake of individuals with CD, validate dietary indices in diverse samples, and explore the utility of these indices in CD assessment and treatment. The co-authors hope this work will stimulate/inspire subsequent interprofessional, dietitian-led research on this topic.

To assess whether antibiotic exposure prenatally and before 2 years of age is associated with subsequent pediatric inflammatory bowel disease (PIBD), as earlier studies diverge substantially in risk estimations or do not include prenatal exposure.

We performed a register-based cohort study including all children in Norway born 2004-2012 until study's end on December 31, 2020. Exposures were defined as dispensed antibiotics to mothers during pregnancy and to children before 2 years of age. Main outcome was International Classification of Diseases, Tenth Revision, code registrations consistent with PIBD.

Among 536 819 children, 797 PIBD cases were identified. The aOR for developing PIBD if exposed to antibiotics before 2 years of age compared with no exposure was 1.33 (95% CI 1.15-1.53), adjusted for sex and prenatal antibiotic exposure. An adjustment for maternal smoking during pregnancy increased the aOR to 1.42 (1.22-1.66), but with minimal changes after further adjustments for potential confounders related to pregnancy, birth, or socioeconomic status. A dose-response association was observed in those receiving more than 2 antibiotic courses (aOR 1.47, 1.25-1.73), and with greater effect estimates for broad-spectrum antibiotics (aOR 2.57, 1.82-3.63). Antibiotic exposure during pregnancy was numerically but not significantly associated with offspring PIBD (aOR 1.15, 0.99-1.34).

Children exposed to antibiotics before 2 years of age were more likely to develop pediatric IBD than controls. Exposure prenatally to maternal antibiotics was numerically but not statistically significant associated to subsequent PIBD.

Background and Objectives: Despite the fact that biologic drugs have transformed inflammatory bowel disease (IBD) treatment, addressing fibrosis-related strictures remains a research gap. This study explored the roles of cytokines, macrophages, and Krüppel-like factors (KLFs), specifically KLF4, in intestinal fibrosis, as well as the interplay of KLF4 with various gut components. Materials and Methods: This study examined macrophage subtypes, their KLF4 expression, and the effects of KLF4 knockdown on macrophage polarization and cytokine expression using THP-1 monocyte models. Co-culture experiments with stromal myofibroblasts and a conditioned medium from macrophage subtype cultures were conducted to study the role of these cells in intestinal fibrosis. Human-induced pluripotent stem cell-derived small intestinal organoids were used to confirm inflammatory and fibrotic responses in the human small intestinal epithelium. Results: Each macrophage subtype exhibited distinct phenotypes and KLF4 expression. Knockdown of KLF4 induced inflammatory cytokine expression in M0, M2a, and M2c cells. M2b exerted anti-fibrotic effects via interleukin (IL)-10. M0 and M2b cells showed a high migratory capacity toward activated stromal myofibroblasts. M0 cells interacting with activated stromal myofibroblasts transformed into inflammatory macrophages, thereby increasing pro-inflammatory cytokine expression. The expression of IL-36α, linked to fibrosis, was upregulated. Conclusions: This study elucidated the role of KLF4 in macrophage polarization and the intricate interactions between macrophages, stromal myofibroblasts, and cytokines in experimental in vitro models of intestinal fibrosis. The obtained results may suggest the mechanism of fibrosis formation in clinical IBD.

Inflammatory bowel disease (IBD) refers to chronic inflammatory disorders of the gut. Ulcerative colitis (UC) and Crohn's disease (CD) are two subtypes of IBD. Evidence suggests that the intestinal microbiota plays a role in the pathogenesis of IBD, so probiotics have garnered a lot of interest as a potential treatment or prevention for IBD. However, clinical evidence of the efficacy of probiotics is still debatable. We performed a literature review. An advanced search considered clinical studies on probiotic for IBD from inception to 2023 in PubMed, Embase, Cochrane Library, and Web of Science. In the treatment of UC with probiotics, only Escherichia coli Nissle 1917 for maintenance treatment of UC in remission, and Bifidobacterium and VSL#3 for induction of remission in patients with mild to moderately active UC have shown strong evidence. Currently, there are no definitive conclusions regarding the effectiveness of probiotics in CD. The mechanism of probiotic treatment for IBD may be related to reducing oxidative stress, repairing the intestinal barrier, regulating intestinal flora balance, and modulating intestinal immune response. Differences in the benefits of probiotics between CD and UC may be attributable to the different lesion extent and immune-mediated pathophysiology. More robust randomized clinical trials are required to validate the efficacy and safety of diverse probiotic strains in IBD.

Intestinal symbiotic bacteria play a key role in the regulation of immune tolerance in inflammatory bowel disease (IBD) hosts. However, the bacterial strains directly involved in this regulation and their related metabolites are largely unknown. We sought to investigate the effects of intestinal microbial metabolites on intestinal epithelium and to elucidate their therapeutic potential in regulating intestinal mucosal inflammation and immune homeostasis. Here, we used metagenomic data from Crohn's disease (CD) patients to analyze the composition of intestinal flora and identify metabolite profiles associated with disease behavior, and used the mouse model of dextran sodium sulfate (DSS)-induced colitis to characterize the therapeutic effects of the flora metabolite acetyl l-carnitine (ALC) on DSS-induced colitis. We found that intraperitoneal injection of ALC treatment could significantly alleviate the symptoms of DSS-induced colitis in mice, including prevention of weight loss, reduction in disease activity index (DAI) scores, increasing of colonic length, reduction in histological scores, and improvement in intestinal barrier function. Further, transcriptome sequencing analysis and gene silencing experiments revealed that the absence of CADM2 abolished the inhibitory effect of ALC on the TLR-MyD88 pathway in colonic epithelial cells, thereby reducing the release of inflammatory factors in colon epithelial cells. And we confirmed a significant downregulation of CADM2 expression in intestinal tissues of CD patients compared to healthy people in a population cohort. In addition, we also found that ALC increased the ratio of Treg cells in colon, and decreased the ratio of Th17 cells and macrophages, thereby improving the immune tolerance of the organism. The proposed study could be a potential approach for the treatment of CD.

The Human Microbiome Project, Earth Microbiome Project, and next-generation sequencing have advanced novel genome association, host genetic linkages, and pathogen identification. The microbiome is the sum of the microbes, their genetic information, and their ecological niche. This study will describe how millions of bacteria in the gut affect the human body in health and disease. The gut microbiome changes in relation with age, with an increase in Bacteroidetes and Firmicutes. Host and environmental factors affecting the gut microbiome are diet, drugs, age, smoking, exercise, and host genetics. In addition, changes in the gut microbiome may affect the local gut immune system and systemic immune system. In this study, we discuss how the microbiome may affect the metabolism of healthy subjects or may affect the pathogenesis of metabolism-generating metabolic diseases. Due to the high number of publications on the argument, from a methodologically point of view, we decided to select the best papers published in referred journals in the last 3 years. Then we selected the previously published papers. The major goals of our study were to elucidate which microbiome and by which pathways are related to healthy and disease conditions.

Ruminococcus gnavus (R. gnavus) is a gram-positive anaerobe commonly resides in the human gut microbiota. The advent of metagenomics has linked R. gnavus with various diseases, including inflammatory bowel disease (IBD), obesity, and diabetes mellitus (DM), which has become a growing area of investigation. The initial focus of research primarily centered on assessing the abundance of R. gnavus and its potential association with disease presentation, taking into account variations in sample size, sequencing and analysis methods. However, recent investigations have shifted towards elucidating the underlying mechanistic pathways through which R. gnavus may contribute to disease manifestation. In this comprehensive review, we aim to provide an updated synthesis of the current literature on R. gnavus in the context of IBD, obesity, and DM. We critically analyze relevant studies and summarize the potential molecular mediators implicated in the association between R. gnavus and these diseases. Across numerous studies, various molecules such as methylation-controlled J (MCJ), glucopolysaccharides, ursodeoxycholic acid (UDCA), interleukin(IL)-10, IL-17, and capric acid have been proposed as potential contributors to the link between R. gnavus and IBD. Similarly, in the realm of obesity, molecules such as hydrogen peroxide, butyrate, and UDCA have been suggested as potential mediators, while glycine ursodeoxycholic acid (GUDCA) has been implicated in the connection between R. gnavus and DM. Furthermore, it is imperative to emphasize the necessity for additional studies to evaluate the potential efficacy of targeting pathways associated with R. gnavus as a viable strategy for managing these diseases. These findings have significantly expanded our understanding of the functional role of R. gnavus in the context of IBD, obesity, and DM. This review aims to offer updated insights into the role and potential mechanisms of R. gnavus, as well as potential strategies for the treatment of these diseases.

The association between gut microbiota and the development of heart failure has become a research hotspot in recent years and the impact of gut microbiota on heart failure has attracted growing interest. From 2006 to 2021, the global research on gut microbiota and heart failure has gradually expanded, indicating a developed and promising research field. There were 40 countries, 196 institutions, and 257 authors involved in the publication on the relationship between gut microbiota and heart failure, respectively. In patients with heart failure, inadequate visceral perfusion leads to ischemia and intestinal edema, which compromise the gut barrier. This subsequently results in the translocation of bacteria and bacterial metabolites into the circulatory system and causes local and systemic inflammatory responses. The gastrointestinal tract contains the largest number of immune cells in the human body and gut microbiota play important roles in the immune system by promoting immune tolerance to symbiotic bacteria. Studies have shown that probiotics can act on gut microorganisms, thereby increasing choline metabolism and reducing plasma TMA and TMAO concentrations, thus inhibiting the development of heart failure. Meanwhile, probiotics induce the production of inflammatory suppressors to maintain gut immune stability and inhibit the progression of heart failure by reducing ventricular remodeling. Here, we review the current understanding of gut microbiota-driven immune dysfunction in experimental and clinical heart failure, as well as the therapeutic interventions that could be used to address these issues.

The prevalence of ulcerative colitis (UC) poses a serious threat to human health. This study showed that fiber-deficient diet (FD) increased the susceptibility of mice to low dosage of DSS-induced UC, and a UC model was established by feeding mice with DSS and FD to evaluate the effect of Scytosiphon lomentaria fucoidan (SLF) on UC. SLF ameliorated the symptoms of UC, as evidenced by increases in colon length, goblet cells and glycoprotein and reduction in inflammatory cell infiltration and intestinal epithelial injury. SLF alleviated oxidative stress and inhibited colonic inflammation by reducing the levels of lipopolysaccharides and pro-inflammatory cytokines and suppressing the activation of nuclear factor kappa B pathway. SLF protected tight junction integrity by reducing the level of myosin light chain kinase and increasing the levels of claudin, zonula occludens-1 and occludin. SLF improved serum metabolites profile and affected multiple metabolic pathways that are crucial to human health, e.g. butanoate metabolism. The underlying mechanism can be associated with modulation of the gut microbiota and metabolites, including increases in short chain fatty acids and reduction in Proteobacteria, Bacteroides and Romboutsia. It suggests that SLF could be developed as a prebiotic polysaccharide to benefit human health by improving intestinal microecology.

Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) have been associated with several inflammatory conditions, including inflammatory bowel diseases (IBDs), and found to have an impact on gut microbiota. In fact, some randomized controlled studies suggest benefits to IBD patients, but others do not. Our aim was to review recent evidence on the effects of omega-3 on IBD and establish the contribution of the gut microbiome. Omega-3 mediate anti-inflammatory effects in IBD through various mechanisms, including suppression of NLR family pyrin domain-containing 3 (NLRP3) inflammasome, Toll-like receptor-4 (TLR4), and nucleotide-binding oligomerization domain 2 (NOD2) signaling; this results in the repression of the nuclear factor-kappa B (Nf-kB) pathway and the secretion of pro-inflammatory cytokines. Omega-3 can also affect gut microbiota and revert the bacterial community to patterns associated with healthy status by increasing short-chain fatty acid (SCFA)-producing bacteria and enhancing the mucosal gut barrier, thus promoting homeostasis. The combination of these immunoregulatory effects and anti-inflammation properties with the promotion of a balanced gut microbiome environment could suggest that omega-3 might benefit IBD patients. Considering the microbiota of IBD patients while using omega-3 might predict and improve omega-3 effectiveness. Combining omega-3 with bacteria-altering therapy, such as probiotics and fecal microbiota transplantation, may further enhance its efficacy; however, further studies are required to elucidate mechanisms and potential preventive or treatment roles of omega-3 in IBD.

During the disease course, most Inflammatory Bowel Disease patients present a condition of malnutrition, undernutrition, or even overnutrition. These conditions are mainly due to suboptimal nutritional intake, alterations in nutrient requirements and metabolism, malabsorption, and excessive gastrointestinal losses. A suboptimal nutritional status and low micronutrient serum levels can have a negative impact on both induction and maintenance of remission and on the quality of life of Inflammatory Bowel Disease patients. We performed a systematic review including all the studies evaluating the connection between nutrition, nutrition status (including undernutrition and overnutrition), micronutrient deficiency, and both disease course and therapeutic response in Inflammatory Bowel Disease patients. This systematic review was performed using PubMed/MEDLINE and Scopus. Four main clinical settings concerning the effect of nutrition on disease course in adult Inflammatory Bowel Disease patients were analyzed (induction of remission, maintenance of remission, risk of surgery, post-operative recurrence, and surgery-related complications). Four authors independently reviewed abstracts and manuscripts for eligibility. 6077 articles were found; 762 duplicated studies were removed. Out of 412 full texts analyzed, 227 were included in the review. The evidence summarized in this review showed that many nutritional aspects could be potential targets to induce a better control of symptoms, a deeper remission, and overall improve the quality of life of Inflammatory Bowel Disease patients.

The gut microbiota consists of a set of microorganisms that colonizes the intestine and ferment fibers, among other nutrients, from the host's diet. A healthy gut microbiota, colonized mainly by beneficial microorganisms, has a positive effect on digestion and plays a role in disease prevention. However, dysregulation of the gut microbiota can contribute to various diseases. The nutrition of the host plays an important role in determining the composition of the gut microbiota. A healthy diet, rich in fiber, can beneficially modulate the gut microbiota. In this sense, oats are a source of both soluble and insoluble fiber. Oats are considered a functional ingredient with prebiotic potential and contain plant proteins, unsaturated fats, and antioxidant compounds. The impact of oat consumption on the gut microbiota is still emerging. Associations between oat consumption and the abundance of Akkermansia muciniphila, Roseburia, Lactobacillus, Bifidobacterium, and Faecalibacterium prausnitzii have already been observed. Therefore, this integrative review summarizes the findings from studies on the relationship between oat consumption, the gut microbiota, and the metabolites, mainly short-chain fatty acids, it produces.

Cognitive function in humans depends on the complex and interplay between multiple body systems, including the hypothalamic-pituitary-adrenal (HPA) axis. The gut microbiota, which vastly outnumbers human cells and has a genetic potential that exceeds that of the human genome, plays a crucial role in this interplay. The microbiota-gut-brain (MGB) axis is a bidirectional signalling pathway that operates through neural, endocrine, immune, and metabolic pathways. One of the major neuroendocrine systems responding to stress is the HPA axis which produces glucocorticoids such as cortisol in humans and corticosterone in rodents. Appropriate concentrations of cortisol are essential for normal neurodevelopment and function, as well as cognitive processes such as learning and memory, and studies have shown that microbes modulate the HPA axis throughout life. Stress can significantly impact the MGB axis via the HPA axis and other pathways. Animal research has advanced our understanding of these mechanisms and pathways, leading to a paradigm shift in conceptual thinking about the influence of the microbiota on human health and disease. Preclinical and human trials are currently underway to determine how these animal models translate to humans. In this review article, we summarize the current knowledge of the relationship between the gut microbiota, HPA axis, and cognition, and provide an overview of the main findings and conclusions in this broad field.

The human intestinal microbiota, also known as the gut microbiota, comprises more than 100 trillion organisms, mainly bacteria. This number exceeds the host body cells by a factor of ten. The gastrointestinal tract, which houses 60%-80% of the host's immune cells, is one of the largest immune organs. It maintains systemic immune homeostasis in the face of constant bacterial challenges. The gut microbiota has evolved with the host, and its symbiotic state with the host's gut epithelium is a testament to this co-evolution. However, certain microbial subpopulations may expand during pathological interventions, disrupting the delicate species-level microbial equilibrium and triggering inflammation and tumorigenesis. This review highlights the impact of gut microbiota dysbiosis on the development and progression of certain types of cancers and discusses the potential for developing new therapeutic strategies against cancer by manipulating the gut microbiota. By interacting with the host microbiota, we may be able to enhance the effectiveness of anticancer therapies and open new avenues for improving patient outcomes.

Inflammatory bowel disease (IBD) is a chronic recurrent inflammation of the gastrointestinal tract (GIT). IBD patients are susceptible to various infections such as viral infections due to the long-term consumption of immunosuppressive drugs and biologics. The antiviral and IBD protective traits of flavonoids have not been entirely investigated. This study objective included an overview of the protective role of flavonoids quercetin and silymarin in viral-associated IBD. Several viral agents such as cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella zoster virus (VZV) and enteric viruses can be reactivated and thus develop or exacerbate the IBD conditions or eventually facilitate the disease remission. Flavonoids such as quercetin and silymarin are non-toxic and safe bioactive compounds with remarkable anti-oxidant, anti-inflammatory and anti-viral effects. Mechanisms of anti-inflammatory and antiviral effects of silymarin and quercetin mainly include immune modulation and inhibition of caspase enzymes, viral binding and replication, RNA synthesis, viral proteases and viral assembly. In the nutraceutical sector, natural flavonoids low bioavailability and solubility necessitate the application of delivery systems to enhance their efficacy. This review study provided an updated understanding of the protective role of quercetin and silymarin against viral-associated IBD.

Cyanidin-3-O-glucoside (C3G), the most widely distributed anthocyanin (ACN) in edible fruits, has been proposed for several bioactivities, including anti-inflammatory, neuro-protective, antimicrobial, anti-viral, anti-thrombotic and epigenetic actions. However, habitual intake of ACNs and C3G may vary widely among populations, regions, and seasons, among individuals with different education and financial status. The main point of C3G absorption occurs in the small and large bowel. Therefore, it has been supposed that the treating properties of C3G might affect inflammatory bowel diseases (IBD), such as ulcerative colitis (UC) and Crohn's disease (CD). IBDs develop through complex inflammatory pathways and sometimes may be resistant to conventional treatment strategies. C3G presents antioxidative, anti-inflammatory, cytoprotective, and antimicrobial effects useful for IBD management. In particular, different studies have demonstrated that C3G inhibits NF-κB pathway activation. In addition, C3G activates the Nrf2 pathway. On the other hand, it modulates the expression of antioxidant enzymes and cytoprotective proteins, such as NAD(P)H, superoxide dismutase, heme-oxygenase (HO-1), thioredoxin, quinone reductase-oxide 1 (NQO1), catalase, glutathione S-transferase and glutathione peroxidase. Interferon I and II pathways are downregulated by C3G inhibiting interferon-mediating inflammatory cascades. Moreover, C3G reduces reactive species and pro-inflammatory cytokines, such as C reactive protein, interferon-γ, tumor necrosis factor-α, interleukin (IL)-5, IL-9, IL-10, IL-12p70, and IL-17A in UC and CD patients. Finally, C3G modulates gut microbiota by inducing an increase in beneficial gut bacteria and increasing microbial abundances, thus mitigating dysbiosis. Thus, C3G presents activities that may have potential therapeutic and protective actions against IBD. Still, in the future, clinical trials should be designed to investigate the bioavailability of C3G in IBD patients and the proper therapeutic doses through different sources, aiming to the standardization of the exact clinical outcome and efficacy of C3G.

Dectin-1 expressed on host immune cells recognizes β-glucans within the cell walls of fungal pathogens and plays an important role in the clearance of fungal infections. However, because β-glucan is masked by an outer layer of mannoproteins, fungal pathogens can evade detection by host immune cells. In this study, a microplate-based screen was developed to identify β-glucan unmasking activity exhibited by botanicals. This screen measures the activity of a reporter gene in response to the transcriptional activation of NF-κB due to the interaction between β-glucan on the fungal cell surface and Dectin-1 present on host immune cells. In this proof-of-concept study, we screened a collection of botanicals (10 plants and some of their reported pure compound actives) used in traditional medicine for their antifungal properties. Several hits were identified in samples that unmasked β-glucan at sub-inhibitory concentrations. The hit samples were confirmed by fluorescent staining with a β-glucan antibody, verifying that the samples identified in the screen did indeed unmask β-glucan. These results indicate that the purported antifungal activities attributed to some botanicals may be due, at least in part, to the presence of compounds that exhibit β-glucan unmasking activity. Enhanced exposure of cell wall β-glucans would allow the host to build resilience against fungal infections by helping the immune system to detect the pathogen and mount a more effective clearance mechanism. This screen, together with direct killing/growth inhibition assays, may therefore serve as a valuable tool for substantiating the use of botanicals in preventing and/or treating fungal infections.

Poor diet, obesity and a sedentary lifestyle have a significant impact on natural microbiota disorders; specifically, the intestinal one. This in turn can lead to a multitude of organ dysfunctions. The gut microbiota contains more than 500 species of bacteria and constitutes 95% of the total number of cells in the human body, thus contributing significantly to the host's resistance to infectious diseases. Nowadays, consumers have turned to purchased foods, especially those containing probiotic bacteria or prebiotics, that constitute some of the functional food market, which is constantly expanding. Indeed, there are many products available that incorporate probiotics, such as yogurt, cheese, juices, jams, cookies, salami sausages, mayonnaise, nutritional supplements, etc. The probiotics are microorganisms that, when taken in sufficient amounts, contribute positively to the health of the host and are the focus of interest for both scientific studies and commercial companies. Thus, in the last decade, the introduction of DNA sequencing technologies with subsequent bioinformatics processing contributes to the in-depth characterization of the vast biodiversity of the gut microbiota, their composition, their connection with the physiological function-known as homeostasis-of the human organism, and their involvement in several diseases. Therefore, in this study, we highlighted the extensive investigation of current scientific research for the association of those types of functional foods containing probiotics and prebiotics in the diet and the composition of the intestinal microbiota. As a result, this study can form the foundation for a new research path based on reliable data from the literature, acting a guide in the continuous effort to monitor the rapid developments in this field.

Bile salt hydrolases are thought to be the gatekeepers of bile acid metabolism. To study the role of BSH in colitis, we investigated the ameliorative effects of different BSH-knockout strains of Lactiplantibacillus plantarum AR113. The results showed that L. plantarum Δbsh 1 and Δbsh 3 treatments did not improve body weight and alleviate the hyperactivated myeloperoxidase activity to the DSS group. However, the findings for L. plantarum AR113, L. plantarum Δbsh 2 and Δbsh 4 treatments were completely opposite. The double and triple bsh knockout strains further confirmed that BSH 1 and BSH 3 are critical for the ameliorative effects of L. plantarum AR113. In addition, L. plantarum Δbsh 1 and Δbsh 3 did not significantly inhibit the increase in pro-inflammatory cytokines or the decrease in an anti-inflammatory cytokine. These results suggest that BSH 1 and BSH 3 in L. plantarum play important roles in alleviating enteritis symptoms.

Inflammatory bowel disease (IBD) is a specific immune-associated intestinal disease. At present, the conventional treatment for patients is not ideal. Probiotics are widely used in the treatment of IBD patients due to their ability to restore the function of the intestinal mucosal barrier effectively and safely. Lactiplantibacillus plantarum subsp. plantarum is a kind of probiotic that exists in the intestines of hosts and is considered to have good probiotic properties. In this study, we evaluated the therapeutic effect of Lactiplantibacillus plantarum subsp. plantarum SC-5 (SC-5) on dextran sulfate sodium (DSS)-induced colitis in C57BL/6J mice. We estimated the effect of SC-5 on the clinical symptoms of mice through a body weight change, colon length, and DAI score. The inhibitory effects of SC-5 on the levels of cytokine IL-1β, IL-6, and TNF-α were determined by ELISA. The protein expression levels of NF-κB, MAPK signaling pathway, and the tight junction proteins occludin, claudin-3, and ZO-1 were verified using Western Blot and immunofluorescence. 16S rRNA was used to verify the modulatory effect of SC-5 on the structure of intestinal microbiota in DSS-induced colitis mice. The results showed that SC-5 could alleviate the clinical symptoms of DSS-induced colitis mice, and significantly reduce the expression of pro-inflammatory cytokines in the colon tissue. It also attenuated the inflammatory response by inhibiting the protein expression of NF-κB and MAPK signaling pathways. SC-5 improved the integrity of the intestinal mucosal barrier by strengthening tight junction proteins. In addition, 16S rRNA sequencing demonstrated that SC-5 was effective in restoring intestinal flora balance, as well as in increasing the relative abundance and diversity of beneficial microbiota. These results indicated that SC-5 has the potential to be developed as a new probiotic candidate that prevents or alleviates IBD.

An imbalance in gut microbiota, termed dysbiosis, has been shown to affect host health. Several factors, including dietary changes, have been reported to cause dysbiosis with its associated pathologies that include inflammatory bowel disease, cancer, obesity, depression, and autism. We recently demonstrated the inhibitory effects of artificial sweeteners on bacterial quorum sensing (QS) and proposed that QS inhibition may be one mechanism behind such dysbiosis. QS is a complex network of cell-cell communication that is mediated by small diffusible molecules known as autoinducers (AIs). Using AIs, bacteria interact with one another and coordinate their gene expression based on their population density for the benefit of the whole community or one group over another. Bacteria that cannot synthesize their own AIs secretly "listen" to the signals produced by other bacteria, a phenomenon known as "eavesdropping". AIs impact gut microbiota equilibrium by mediating intra- and interspecies interactions as well as interkingdom communication. In this review, we discuss the role of QS in normobiosis (the normal balance of bacteria in the gut) and how interference in QS causes gut microbial imbalance. First, we present a review of QS discovery and then highlight the various QS signaling molecules used by bacteria in the gut. We also explore strategies that promote gut bacterial activity via QS activation and provide prospects for the future.

Inflammatory bowel disease can cause pathological changes of certain organs, including the gut and brain. As the major degradation route of tryptophan (Trp), Kynurenine (Kyn) pathway are involved in multiple pathologies of brain. This study sought to explore the effects of Dextran sulphate sodium (DSS)-induced colitis on serum and brain Trp metabolism (especially the Kyn pathway) and its mechanisms. We induced acute colitis and sub-chronic colitis with 3% DSS and 1% DSS respectively and found more severe intestinal symptoms in acute colitis than sub-chronic colitis. Both of the colitis groups altered Trp-Kyn-Kynurenic acid (Kyna) pathway in serum by regulating the expression of rate-limiting enzyme (IDO-1, KAT2). Interestingly, only 3% DSS group activated Trp-Kyn pathway under the action of metabolic enzymes (IDO-1, TDO-2 and KAT2) in brain. Furthermore, intestinal flora 16S rRNA sequencing showed significantly changes in both DSS-induced colitis groups, including microbial diversity, indicator species, and the abundance of intestinal microflora related to Trp metabolism. The functional pathways of microbiomes involved in inflammation and Trp biosynthesis were elevated after DSS treatment. Moreover, correlation analysis showed a significant association between intestinal flora and Trp metabolism (both in serum and brain). In conclusion, our study suggests that DSS-induced acute colitis causes dysregulation of Trp-Kyn-Kyna pathways of Trp metabolism in serum and brain by affecting rate-limiting enzymes and intestinal flora.