Overtraining Syndrome (OTS) is a condition resulting from excessive physical activity without adequate recovery, predominantly affecting elite athletes and military personnel. While overreaching can be a temporary state, non-functional overreaching may progress to chronic OTS. This review explores various hypotheses regarding the pathogenesis of OTS, including glycogen depletion, dysregulated cytokine response, oxidative stress, and alterations in the autonomic nervous system function. It also highlights the systemic impact of OTS on multiple organ systems, immune function, and overall health, linking the condition to chronic inflammation and an increased disease susceptibility. Additionally, it addresses the role of the gut microbiome in health modulation through physical activity.

This narrative review was conducted through a structured search of peer-reviewed journal articles in databases such as PubMed, Web of Science, and Google Scholar, focusing on studies involving human participants and published in English.

OTS has systemic effects on multiple organ systems, immune function, and overall health, leading to chronic inflammation and increased disease susceptibility. Athletes with OTS exhibit higher morbidity rates, influenced by factors such as sleep deprivation and stress. The review also emphasizes the role of the gut microbiome as a significant modulator of health through physical activity.

Balanced training and recovery are crucial for preventing OTS and maintaining optimal health and quality of life in physically active individuals. Understanding the complex pathophysiology of OTS is essential for developing effective prevention and treatment strategies.

This study investigated the relationship between BMI and microorganism profiles, with a particular focus on gut microorganisms in patients with PJI following total hip arthroplasty (THA). It also explored comorbidities, that may contribute to these variations.

This study included all patients treated at our institution for a PJI of a THA between 1996 and 2021. Patients were categorized into four distinct BMI groups: <30; 30-34.9; 35-39.9; ≥ 40. Bivariate and logistic regression analysis were conducted, with presentation of odds ratio (OR) and 95% confidence interval (CI).

A total of 3645 hip PJI cases were recruited for the final analysis. Patients with a BMI ≥ 40 had approximately a ten fold higher risk for Streptococcus dysgalactiae (p < 0.001; OR = 9.92; 95% CI 3.87-25.44) and a seven fold higher risk for Proteus mirabilis (p < 0.001; OR = 7.43; 95% CI 3.13-17.67) and Klebsiella pneumoniae (p < 0.001; OR = 6.9; 95% CI 2.47-19.31). Furthermore, polymicrobial infections (p < 0.001; OR = 2.17; 95% CI 1.50-3.15) were found to be significantly more prevalent in patients with a BMI ≥ 40.

Obese patients (BMI ≥ 30) displayed a distinct microorganism profile in hip PJIs, mainly dominated by Firmicutes and Proteobacteria. Comorbidities such as diabetes, hypertension, and hyperlipidaemia may contribute to a leaky gut syndrome, increasing PJI risk caused by gut microorganisms. Optimizing comorbidities may help reduce the risk of hip PJI. Further research is needed to clarify the relationship between obesity, gut microbiome alterations and hip PJI development.

Diabetic foot infections (DFIs) contribute to the global disability burden. Beta-lactams are the most commonly used antibiotics for treating DFIs. However, the use of antibiotics may lead to disruption of the healthy balance of the gut microbiota, causing dysbiosis.

Patients with infected diabetic foot ulcers (iDFUs) were treated with two kinds of beta-lactams (amoxicillin/clavulanic acid or ceftazidime) according to microbial sensitivity of causative agents via bolus or continuous administration modes. Changes in the gut microbiome of patients were analyzed. Diabetic patients without iDFUs were used as a control group. 16 S ribosomal RNA gene amplicon sequencing was performed on stool samples collected from participants.

Alpha diversity and beta diversity of gut microbiota of treated patients did not show significant differences between bolus and continuous modes. However, significant differences were observed between gut microbiota diversity of treated patients and control group. PCoA plots showed individualized responses of the patient's gut microbiota to antibiotics at different times using both administration forms associated with the pre-treatment state of microbiota composition. Enterococcus, Sellimonas, and Lachnoclostridium were the common bacterial markers differentially abundant in the gut microbiota of antibiotic-treated patients with iDFUs while Roseburia, Dorea, and Monoglobus were mainly abundant in the gut microbiota of patients without iDFUs. Predicted pathways like "Transporters", "ABC transporters" and "Phosphotranspherase system (PTS)" were upregulated in the gut microbiome of patients treated with bolus regime which may lead to increased intestinal barrier permeability.

The present study reported alterations in gut microbiota composition and functionality and provided the bacterial markers as well as potential metabolic signatures associated with each administration mode in patients with iDFUs, which may be used as a reference set for future studies of the effect of antibiotics administration on the gut microbiome of patients with iDFUs. This study shed light on the importance of understanding the effect of antibiotic administration form on gut microbiome in patients with iDFUs.

The DFIATIM Clinical Trial (Full title: "Rationalisation of ATB therapy in diabetic foot infection and its impact on the intestinal microbiota") is submitted to the European Union Clinical Trials Database under the EudraCT Number: 2019-001997-27. The date of registration is July 17th, 2020.

Atherosclerosis (AS) is the most common cardiovascular disease (CVD), despite an overall declining incidence, AS remains a leading cause of death worldwide. The ZeXieYin formula (ZXYF), one of the thirteen formulas recorded in HuangDiNeiJin, a classical book of Traditional Chinese Medicine (TCM), has previously demonstrated efficacy in reducing blood lipids and combating AS. However, the precise mechanism by which it regulates blood lipids remains unclear. Given the close correlation between bile acid metabolism and cholesterol metabolism, it is imperative to elucidate the intrinsic mechanisms through which ZXYF treats AS.

This study aims to investigate the pivotal role of enterohepatic bile acid circulation in enhancing intestinal barrier function and mitigating AS by ZXYF.

The AS model was established by subjecting male ApoE-/- mice to a high-fat diet (HFD). Moreover, to determine the impact of ZXYF on the integrity of the intestinal barrier, we quantified proinflammatory cytokines using RT-qPCR and ELISA. Additionally, we identified tight-junction proteins in the ileal tissues through IF. Finally, the intestinal flora metabolite and fecal bile acid composition were analyzed using 16S rRNA analysis, untargeted metabolomics analysis, and targeted metabolomics analysis.

The ZXYF significantly improved dyslipidemia and alleviated the formation of arterial plaques in AS mice. Furthermore, the administration of ZXYF resulted in a concurrent reduction in circulating lipopolysaccharide (LPS) levels and downregulation of pro-inflammatory cytokine mRNA expression in the ileum. Additionally, there was an enhancement observed in the expression of tight junction proteins within the intestinal tissue of AS mice. Further studies found that ZXYF significantly elevated the total bile acids (TBA) and total cholesterol (TC) levels in the fecal of AS mice. The untargeted and targeted metabolomic analyses further revealed that ZXYF exerts regulatory effects on bile acid phenotype by decreasing secondary bile acids (SBAs) levels through modulation of gut microbiota composition, such as enrichment of Akkermansia (AKK) abundance, and inhibition of enterohepatic circulation of bile acids. ZXYF specifically increased the expression of hepatic bile acid synthesis enzymes CYP7A1 by modulating the FXR/FGF15 signaling pathway, thereby promoting enhanced de novo bile acid synthesis and facilitating cholesterol catabolic excretion.

The findings of our research indicate that ZXYF exerts a defensive role in the advancement of AS. The mechanism underlying the role of ZXYF in combating AS is closely associated with gut microbiota reshaping and regulation of enterohepatic bile acid circulation.

Short-chain fatty acids (SCFAs), the primary metabolites produced by the microbial fermentation of dietary fibers in the gut, have a key role in protecting gut health. Increasing evidence indicates SCFAs can exert effects on distant tissues and organs beyond the gut via blood circulation. Osteoarthritis (OA) is a chronic inflammatory joint disease that severely diminishes the physical function and quality of life. However, effective clinical treatments for OA remain elusive. Recent studies have shown that SCFAs can exert beneficial effects on damaged joints in OA. SCFAs can mitigate OA progression by preserving intestinal barrier function and maintaining the integrity of cartilage and subchondral bone, suggesting that they have substantial potential to be the adjunctive treatment strategy for OA. This review described the SCFAs in the human body and their cellular signaling mechanism, and summarized the multiple effects of SCFAs (especially butyrate, propionate, and acetate) on the prevention and treatment of OA by regulating the gut-joint axis, providing novel insights into their promising clinical applications.

Historically, multigenerational health and disease transmission have primarily focused on genetic inheritance. However, the discovery that beneficial microorganisms known as commensal microbiota outnumber human genes tenfold has reshaped this perspective, highlighting their critical role in maintaining homeostasis and protecting against pathogens. Unlike the human genome, commensal microbiota is not genetically inherited but is acquired anew with each generation. with initial gut colonization playing a pivotal role in shaping an infant's immune system, neurodevelopment, and long-term health, all heavily influenced by maternal factors. In this review, we examine emerging research on maternal microbial influences on the fetus beginning in utero. We provide an updated overview of the current insights into the impact of the vaginal microbiome during parturition on offspring immunity and discuss the potential long-term health implications for infants born via cesarean section. We explore the advantages and limitations of techniques designed to mitigate these effects, such as vaginal seeding and emphasize that the development of the neonatal immune system is a dynamic process influenced by maternal factors beyond birth, including the transfer of microbiota through breast milk and skin contact. Finally, we present gaps in current research and propose future research directions to deepen our understanding of the impacts of the maternal microbiome on her child. Together, these insights demonstrate how maternal influence on offspring health and immunity extends beyond genetic factors, encompassing the transmission of microbiota, which, in turn, has profound long-term implications for health and disease resilience, offering a novel perspective on intergenerational health dynamics.

The increasing global burden of allergic diseases and multimorbidity underscores the urgent need for innovative strategies to strengthen immune health. This review explores the complex relationships among nutrition, gut microbiota, immune regulation, allergic diseases, and multimorbidity. It highlights how targeted nutritional and microbial interventions may influence disease outcomes. Dietary components and microbial metabolites dynamically modulated immune function, highlighting the critical role of the gut-immune-metabolism axis in disease pathogenesis and management. Personalized nutrition, guided by advances in diagnostics such as component-resolved diagnostics, basophil activation tests, and epigenetic biomarkers, allows for precise dietary interventions tailored to individual allergy phenotypes and multimorbidity profiles. The Mediterranean diet, breastfeeding, and microbiota-targeted therapies have emerged as effective strategies to enhance immune resilience, reduce inflammation, and manage allergic reactions. Technological advancements, including artificial intelligence-driven dietary assessments, wearable devices, and mobile applications, have further revolutionized personalized dietary management, enabling real-time, precise nutritional monitoring and intervention. Despite these advances, challenges in implementing personalized nutrition persist, including variability in dietary patterns, cultural and socioeconomic factors, and accessibility concerns. Future research should focus on long-term interventional and longitudinal studies to validate precision nutrition strategies and enhance clinical applicability. This integrative approach, combining nutrition, microbiome science, technology, and personalized healthcare, holds substantial promises for sustainable disease prevention and enhanced immune resilience across diverse populations.

In recent years, the prevalence of chronic liver diseases, particularly Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), has increased significantly. This upward trend is largely associated with lifestyle-related factors such as unhealthy dietary habits, physical inactivity, and various environmental influences. Among the key elements contributing to the pathogenesis of MASLD, the integrity of the intestinal epithelial barrier emerges as a critical determinant, given its central role in maintaining immune homeostasis along the gut-liver axis. Disruption of this barrier, often driven by excessive consumption of saturated fats and refined carbohydrates in combination with low dietary fiber intake, can lead to microbial dysbiosis. This imbalance in the gut microbiota triggers immune dysregulation and promotes systemic inflammation, thereby exacerbating hepatic injury. This review discusses the contribution of epithelial barrier dysfunction to the development and progression of MASLD, with a particular focus on how increased intestinal permeability may initiate and sustain chronic liver inflammation. Additionally, the influence of dietary and environmental factors on epithelial integrity, immune responses, and the inflammatory cascade is addressed. A better understanding of the complex interplay between gut barrier impairment, immune modulation, and liver pathology may offer valuable insights into MASLD pathophysiology and contribute to the development of more targeted therapeutic strategies.

Impaired gut barrier function plays a pivotal role in the pathophysiology of irritable bowel syndrome (IBS), particularly in IBS with diarrhea. Mucoprotectants, such as xyloglucan, gelatin tannate and pea protein tannins, offer a novel therapeutic approach by restoring intestinal permeability and reducing inflammation. This review assesses preclinical and clinical evidence supporting mucoprotectants in IBS with diarrhea management. Preclinical studies indicate their efficacy in reducing intestinal permeability and inflammation, while clinical trials demonstrate improvements in stool consistency, abdominal pain and bloating. Despite these promising results, comparative studies are needed to establish the superiority of specific mucoprotectants and their optimal use in clinical practice.

Fertility is a dynamic, multifactorial process governed by hormonal, immune, metabolic, and environmental factors. Recent evidence highlights the gut microbiota as a key systemic regulator of reproductive health, with notable impacts on endometrial function, implantation, pregnancy maintenance, and the timing of birth. This review examines the gut-endometrial axis, focusing on how gut microbial communities influence reproductive biology through molecular signaling pathways. We discuss the modulatory roles of microbial-derived metabolites-including short-chain fatty acids, bile acids, and tryptophan catabolites-in shaping immune tolerance, estrogen metabolism, and epithelial integrity at the uterine interface. Emphasis is placed on shared mechanisms such as β-glucuronidase-mediated estrogen recycling, Toll-like receptor (TLR)-driven inflammation, Th17/Treg cell imbalance, and microbial translocation, which collectively implicate dysbiosis in the etiology of gynecological disorders including endometriosis, polycystic ovary syndrome (PCOS), recurrent implantation failure (RIF), preeclampsia (PE), and preterm birth (PTB). Although most current evidence remains correlational, emerging insights from metagenomic and metabolomic profiling, along with microbiota-depletion models and Mendelian randomization studies, underscore the biological significance of gut-reproductive crosstalk. By integrating concepts from microbiology, immunology, and reproductive molecular biology, this review offers a systems-level perspective on host-microbiota interactions in female fertility.

Dysbiosis, characterized by a microbial imbalance, particularly within the gut microbiota, has emerged as a significant health concern linked to various diseases. This study analyzed 8097 patent documents from The Lens database (2005-2024) to examine global innovation trends in dysbiosis management. The patent filings showed exponential growth, peaking at 1222 documents in 2022, with the United States leading in publications (4361 documents). The analysis revealed three primary innovation clusters: bacterial-based therapeutics (44.8% of patents), specific therapeutic applications (27.6%), and diagnostic methods (15.9%). The disease associations predominantly included inflammatory conditions, infections, and cancer. The patent classifications highlighted a significant focus on probiotic development and microbiota modulation. The surge in patent activity since 2014 correlates with advances in DNA sequencing technology and the growing recognition of dysbiosis's role in human health. This analysis provides valuable insights into the evolving landscape of microbiome therapeutics and future directions for dysbiosis management.

Intestinal senescence, often characterized by increased oxidative stress, is linked to gastrointestinal disorders such as inflammatory bowel disease and colorectal cancer. While previous studies have suggested that diets rich in food additives, such as the emulsifier Polysorbate 80 (P80), may influence gut health, the impact of P80 exposure on intestinal senescence remains unclear. This study aimed to explore the effects of P80 on intestinal senescence in a senescence-accelerated mouse prone model. The results revealed that P80 exposure could damage the intestinal barrier, induce oxidative stress, and accelerate intestinal senescence. Mechanistically, P80 activated the peroxisome proliferator-activated receptor-α (PPARα) and fatty acid-binding protein 1 (FABP1) axis, increasing intestinal fatty acid absorption and triggering lipotoxicity, which promoted senescence. Additionally, P80 exacerbated D-galactose-induced epithelial cell senescence and lipid accumulation via the PPARα signalling pathway. Importantly, the PPARα antagonist GW6471 mitigated fatty acid uptake and reduced senescence in the intestine. In conclusion, the emulsifier P80 accelerated intestinal senescence by regulating the PPARα-FABP1 axis to induce intestinal fatty acid uptake and lipotoxicity, suggesting new insights into the adverse effects of food additives on gut health.

Background: Despite its omnipresence, paediatric pain remains poorly understood and documented, especially in low-income countries. Such pain can be a symptom of long-term subclinical conditions such as systemic chronic inflammation (SCI). The latter can be related to malnutrition. Aim: To explore a potential association between paediatric pain and malnutrition in low-income countries. Methods: Narrative review, including a literature search in the PubMed, EMBASE, Web of Science and Scopus databases (update 24 March 2025). The search query comprised controlled terminology and free text words relating to 'Malnutrition', 'Pain', 'SCI' and 'Paediatric'. Results: To comprehend the complex relation between malnutrition and paediatric pain, associations between (1a) malnutrition, and nociceptive brain development, (1b) malnutrition, the gut microbiome and SCI, and (2) SCI and pain were explored. (1a) Early noxious exposure (e.g. malnutrition-related SCI) can cause long-term alterations in pain perception, brain function and structures. The consequences of malnutrition on the nociceptive brain depend on the life-cycle. (1b) Moderate acute malnutrition causes chronic inflammation and exaggerated inflammatory responses. Such responses could indicate hyper-inflammatory phenotypes. (2) Systemic-induced inflammation causes a widespread increase in musculoskeletal pain sensitivity. Conclusion: Malnutrition could contribute to the development of a nociceptive brain and SCI. Malnutrition-related SCI could induce changes in pain perception/thresholds, and predispose to developing chronic pain. If a relation between malnutrition and SCI predisposes children to develop pain, the prevailing biophysical approach needs revision. A multidimensional interdisciplinary approach seems more relevant. Such approach includes social, cognitive, socioeconomic, lifestyle, nutritional (e.g. integrating nutritional and microbiome-targeted interventions) and environmental dimensions.

(1) Background: Tannacomp® is a drug consisting of tannin albuminate, a complex of tannic acid (TA) and ethacridine lactate (Eta) used for treating acute and traveler's diarrhea. TA is thought to modulate gastrointestinal barrier function, but the underlying mechanisms and whether Eta has similar effects remains unclear. (2) Methods: to investigate the effects of TA and Eta on the intestinal barrier, stress responses were induced in murine intestinal organoids by lipopolysaccharide (LPS) exposure or withdrawal of growth factors from cell culture medium (GFRed). Further, organoids were exposed to either TA (0.01 mg/mL) or Eta (0.002 mg/mL) and markers of inflammatory response and gut barrier function were assessed. (3) Results: TA and Eta reduced several inflammatory markers such as interleukin 6, interleukin 1β, tumor necrosis factor α, and myeloid differentiation primary response 88 in stressed organoids. In addition, TA and Eta attenuated LPS- and GFRed-mediated gut barrier dysfunctions, with normalization of tight junction, adherent junction and mucin gene expression and reduction of Nod2- and matrix metalloproteinase 7-dependent activation of antimicrobial peptides. (4) Conclusions: our data show that TA and Eta modulate markers of inflammation and the intestinal barrier and suggest novel mechanisms of action of this drug that could broaden its treatment indications.

Fecal calprotectin (FC) is a biomarker of intestinal inflammation widely used in the assessment of gastrointestinal disorders. However, its role in chronic kidney disease (CKD) remains unclear. Given the growing recognition of the gut-kidney axis in CKD pathophysiology, this study aimed to investigate the association between FC levels, systemic inflammation, renal outcomes, and mortality in CKD patients.

We enrolled a total of 515 CKD patients who underwent fecal calprotectin measurement between 2016 and 2023. After applying the exclusion criteria (inflammatory bowel disease, ongoing renal replacement therapy, or incomplete laboratory data), 260 patients were included in the final analysis and stratified into low-FC (<102 μg/g, n = 130) and high-FC (≥102 μg/g, n = 130) groups based on the median FC value. Factors associated with kidney disease progression and patient survival were analyzed.

Patients in the high-FC group (≥102 μg/g) were significantly older (72.8 ± 14.63 vs. 64.02 ± 18.15 years, p < 0.0001) and had a higher prevalence of diabetes mellitus (55.38% vs. 42.31%, p = 0.0349), heart failure (21.54% vs. 7.69%, p = 0.0016), and history of acute kidney injury (33.85% vs. 18.46%, p = 0.0048). Elevated FC was independently associated with increased mortality risk (hazards ratio [HR] 1.658, 95% confidence interval [CI] 1.034-2.658, p = 0.0357) with higher mortality rates (48.36 vs. 18.46 per 100,000 person-years). Subgroup analyses revealed stronger associations between FC and mortality in males (HR 2.160, 95% CI 1.046-4.463, p = 0.0375), elderly patients (≥75 years) (HR 2.122, 95% CI 1.209-3.725, p = 0.0088), and non-diabetic patients (HR 2.487, 95% CI 1.141-5.421, p = 0.0219). While FC was not significantly associated with end-stage kidney disease (ESKD) progression (odds ratio [OR] 1.289, 95% CI 0.455-3.650, p = 0.6323), higher FC levels paradoxically predicted slower estimated glomerular filtration rate (eGFR) decline (OR 2.763, 95% CI 1.139-6.699, p = 0.0245). Combined analysis revealed patients with both elevated FC and high-sensitivity C-reactive protein (hs-CRP) had the highest mortality risk (HR 3.504, 95% CI 1.163-10.554, p < 0.0001) compared to those with low levels of both markers.

FC is a potential prognostic biomarker for mortality in CKD patients, independently of traditional inflammatory markers. Further research is warranted to elucidate the mechanisms underlying its paradoxical relationship with renal outcomes and its potential role in risk stratification and therapeutic targeting in CKD.

Heart failure (HF) has become an immense health concern affecting almost 1-2% of the population globally. It is a complex syndrome characterized by activation of the sympathetic nervous system and the Renin-Angiotensin-Aldosterone (RAAS) axis as well as endothelial dysfunction, oxidative stress, and inflammation. The recent literature points towards the interaction between the intestinal flora and the heart, also called the gut-heart axis. The human gastrointestinal tract is naturally inhabited by various microbes, which are distinct for each patient, regulating the functions of many organs. Alterations of the gut microbiome, a process called dysbiosis, may result in systemic diseases and have been associated with heart failure through inflammatory and autoimmune mechanisms. The disorder of intestinal permeability favors the translocation of microbes and many metabolites capable of inducing inflammation, thus further contributing to the deterioration of normal cardiac function. Besides diet modifications and exercise training, many studies have revealed possible gut microbiota targeted treatments for managing heart failure. The aim of this review is to demonstrate the impact of the inflammatory environment induced by the gut microbiome and its metabolites on heart failure and the elucidation of these novel therapeutic approaches.

Meteorin-like (Metrnl), also known as Subfatin, IL-41, or Cometin, is a secreted protein predominantly expressed in the intestinal epithelium. The intestinal barrier, primarily consisting of epithelial cells connected by tight junctions, is essential for maintaining gut homeostasis by preventing harmful substances from entering the body. Despite Metrnl's high expression in the intestine, its role in barrier function remains unclear. In this study, we investigated Metrnl's role in intestinal barrier function using both loss-of-function (using global and intestinal epithelium-specific knockout mice) and gain-of-function (using intestinal epithelium-specific overexpression mice) approaches. Our findings showed that Metrnl deficiency disrupted tight junctions between enterocytes and exacerbated endotoxin-induced barrier dysfunction. Mechanistically, Metrnl deficiency triggered activation of the IKKβ/IκBα/NFκB signaling pathway, leading to increased MLCK expression and MLC phosphorylation. The NFκB inhibitor PDTC reversed this effect both in vivo and in vitro. Macrophages played an essential role in Metrnl's intestinal barrier protective effects during endotoxemia, but were not necessary in burn-induced barrier injury, suggesting potential differences in mechanism between these conditions. Notably, recombinant Metrnl protein administration protected against barrier dysfunction, and genetic overexpression of Metrnl in enterocytes preserved barrier function and alleviated DSS-induced colitis. These findings establish Metrnl as a key regulator of intestinal barrier integrity through the IKKβ/IκBα/NFκB/MLCK/MLC pathway, highlighting its potential therapeutic value in treating barrier dysfunction disorders. Intestinal barrier dysfunction triggers, such as endotoxin and severe burns, may induce the release of Metrnl from vascular endothelium. This leads to an increase in circulating Metrnl. Both circulating Metrnl and local Metrnl inhibit inflammation and the IKKβ/IκBα/NFκB/MLCK/MLC signaling pathway in enterocytes, thereby protecting tight junctions from disruption caused by endotoxin or burns.

Bone broth is a traditional nutrient revered by different people from ancient times to the modern era as a remedy for various illnesses. This review investigates the nutritional components of bone broth, focusing primarily on the most abundant amino acids and minerals saturated in bone broth and their impact on health, particularly in the context of intestinal barrier integrity, intestinal permeability, inflammation, and their application in inflammatory bowel disease. Through comprehensive reviews of animal and human studies, this research highlights that bone broth includes amino acids (glutamine, glycine, proline, histidine, arginine), minerals (Ca, P, K, Mg, Zn) that are beneficial and not just a traditional remedy, resolving questions that have been posed for generations. The benefits documented for components in bone broth support the enhancement of gut health, alleviate inflammation in the intestinal barrier, improve intestinal barrier function in health and disease states, particularly in inflammatory bowel disease, as well as enhancing nutrient absorption. Bone broth offers a nutrient-dense option for enhancing overall health and may offer an alternative to dietary supplements with claims for enhanced gut health. We aim to foster interest in and provide evidence to substantiate claims for bone broth as a potential remedy, particularly for maintaining remission in conditions like IBD and possibly functional diarrhea and to encourage further research.

This study aimed to evaluate if the intestinal permeability is associated with overweight/obesity with or without metabolic syndrome (MetS) and correlate intestinal permeability parameters with cardiovascular risk factors.

This was a cross-sectional study that individuals were divided in three groups: 1) controls (n = 34), 2) overweight/obesity (n = 29), and 3) overweight/obesity + MetS (n = 29). Anthropometric and blood biochemical parameters were used to estimate cardiovascular risk factors. Intestinal permeability was evaluated using the lactulose/mannitol test in urine samples analyzed by High Performance Liquid Chromatography with Pulsed Amperometry Detection. Correlations between intestinal permeability and anthropometric and biochemical parameters were evaluated using Spearman's correlations (r2). Logistic regression models were performed to elucidate variables associated with intestinal permeability parameters. The percentage of urinary excretion of lactulose, mannitol, and the lactulose/mannitol ratio was similar between the studied groups. The percentage of urinary mannitol excretion was positively associated with diastolic blood pressure (r2 = 0.24, p = 0.23), fasting glucose (r2 = 0.26, p = 0.013), fasting insulin (r2 = 0.25, p = 0.015) and HOMA-IR (r2 = 0.26, p = 0.012). The logistic regression showed fasting insulin was associated with a higher mannitol urinary excretion (AOR = 1.08, 95 % CI = 1.02-1.14).

Intestinal permeability was not disrupted in overweight/obesity and MetS, however the results suggest that the increased cardiovascular risk factors were associated with a higher intestinal absorption area. Further studies should investigate other intestinal parameters related to overweight/obesity and MetS in humans.

Claudin-2 (CLDN2), a tight junction protein, is predominantly found in leaky epithelial cell layers where it plays a pivotal role in forming paracellular pores necessary for the efficient transport of cations and water. Its abundance is intricately regulated by upstream signals, modulating its synthesis, transport, and localization to adapt to diverse environmental changes. Aberrant expression levels of CLDN2 are observed in numerous pathological conditions including cancer, inflammation, immune disorders, fibrosis, and kidney and biliary stones. Recent advances have uncovered the mechanisms by which the loss or restoration of CLDN2 affects functions such as epithelial barrier, cell proliferation, renewal, migration, invasion, and tissue regeneration. This exerts a dual-directional influence on the pathogenesis, perpetuation, and progression of diseases, indicating the potential to both accelerate and decelerate the course of disease evolution. Here, we discuss these nuanced bidirectional regulatory effects mediated by CLDN2, and how it may contribute to the progression or regression of disease when it becomes unbalanced.

Hyperlipidemia, a metabolic disorder marked by dysregulated lipid metabolism, is a key contributor to the onset and progression of various chronic diseases. Maintaining normal lipid metabolism is critical for health, as disruptions lead to dyslipidemia. The gut and liver play central roles in lipid homeostasis, with their bidirectional communication, known as the gut-liver axis, modulated by bile acids (BAs), gut microbiota, and their metabolites. BAs are essential for regulating their own synthesis, lipid metabolism, and anti-inflammatory responses, primarily through the farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5). Available evidence suggests that high-fat diet-induced the gut microbiota dysbiosis can induce "leaky gut," allowing toxic microbial metabolites to enter the liver via portal circulation, triggering liver inflammation and lipid metabolism disturbances, ultimately leading to hyperlipidemia. Extensive studies have highlighted the roles of probiotics and Traditional Chinese Medicine (TCM) in restoring gut-liver axis balance and modulating lipid metabolism through regulating the levels of lipopolysaccharides, short-chain fatty acids, and BAs. However, the therapeutic potential of probiotics and TCM for hyperlipidemia remains unclear. Here, firstly, we explore the intricate interplay among gut microbiota and metabolites, lipid metabolism, gut-liver axis, and hyperlipidemia. Secondly, we summarize the mechanisms by which probiotics and TCM can alleviate hyperlipidemia by altering the composition of gut microbiota and regulating lipid metabolism via the gut-liver axis. Finally, we emphasize that more clinical trials of probiotics and TCM are necessary to examine their effects on lipid metabolism and hyperlipidemia.

Leaky gut, an increased intestinal permeability, has been described in many diseases. We have recently demonstrated that neuropeptides such as orexin in the brain improved leaky gut, suggesting that the brain is involved in maintaining intestinal barrier function. It has been suggested that AMPK in the hypothalamus play a role in food intake. Because the hypothalamus is involved in the regulation of not only feeding behavior but also gut function, the present study was performed to clarify a hypothesis that AMPK in the brain regulate gut barrier function. Colonic permeability was determined by quantifying the absorbed Evans blue within the colonic tissue in rats. Intracisternal AICAR, an AMPK activator, could reduce LPS-induced colonic hyperpermeability while peripherally administered AICAR failed to change it. The improvement of colonic hyperpermeability by intracisternal AICAR was blocked by intracisternal but not subcutaneous compound C, AMPK inhibitor, atropine or vagotomy. The improvement of colonic hyperpermeability by intracisternal AICAR was blocked by intracisternal orexin receptor antagonist but not oxytocin or GLP-1 receptor antagonist. Intracisternal compound C prevented brain oxytocin or GLP-1 but not orexin-induced improvement of colonic hyperpermeability. These results suggest that activation of brain AMPK is capable of reducing colonic hyperpermeability through brain orexin signaling and the vagus nerve. In addition, endogenous AMPK in the brain may mediate the oxytocin or GLP-induced improvement of colonic hyperpermeability. We would suggest that improvement of leaky gut by activation of brain AMPK may play a role in leaky gut-related diseases.

Endogenous ethanol production, or auto-brewery syndrome (ABS), is a rare condition of the human alimentary canal that results in intoxication without alcohol consumption. Despite its clinical significance, ABS remains largely undiagnosed because of a lack of awareness among clinicians. Published cases have reported extensive biopsychosocial comorbidities accompanying delayed diagnosis and incomplete management; these include social rejection and family separation, court-ordered alcohol rehabilitation and psychiatric admission, legal and employment ramifications, and deteriorating mental health and suicidality. In this mini review, we aim to educate and enlighten clinicians by discussing literature findings pertaining to the pathophysiological mechanisms of gut dysbiosis due to overgrowth of Saccharomyces cerevisiae, E. coli and Klebsiella, impaired intestinal barrier function, and dysregulation of the hypothalamic-pituitary-adrenal axis. Furthermore, we discuss recently discovered associations with sleep quality and mood disorders and explore the medical sequelae of metabolic dysfunction-associated fatty liver disease and metabolic dysfunction-associated steatohepatitis. Drawing on these data, we propose protocols for initial care in the emergency room, subsequent critical care, diagnostic testing with glucose challenge testing, and definitive microbiological testing during the acute phase of illness. We also present an empirical treatment outline while awaiting confirmation of causative organisms and sensitivities.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major cause of liver disease worldwide, and our understanding of its pathogenesis continues to evolve. MASLD progresses from steatosis to steatohepatitis, fibrosis, and cirrhosis, and this Review explores how the gut microbiome and their metabolites contribute to MASLD pathogenesis. We explore the complexity and importance of the intestinal barrier function and how disruptions of the intestinal barrier and dysbiosis work in concert to promote the onset and progression of MASLD. The Review focuses on specific bacterial, viral, and fungal communities that impact the trajectory of MASLD and how specific metabolites (including ethanol, bile acids, short chain fatty acids, and other metabolites) contribute to disease pathogenesis. Finally, we underscore how knowledge of the interaction between gut microbes and the intestinal barrier may be leveraged for MASLD microbial-based therapeutics. Here, we include a discussion of the therapeutic potential of prebiotics, probiotics, postbiotics, and microbial-derived metabolites.

Probiotics, live microorganisms with multiple health benefits, have gained popularity for their roles in maintaining daily health and treating a variety of diseases. However, they have the potential to be opportunistic pathogens in some conditions. This review delves into the intrinsic and extrinsic risks associated with probiotics. Intrinsic risks involve the production of harmful substances, such as toxins and invasive factors, biofilm formation, bacteria emboli, antibiotic resistance with relevant genetic materials, genetic plasticity, and metabolic issues, while extrinsic risks include problems in regulatory oversight and public awareness, host health status and appropriately administration. It emphasizes the need for a balanced view of their therapeutic benefits and potential hazards, advocating for further research to understand the complex interactions between probiotics and the human microbiome, to optimize the safety and efficacy of probiotics.

Intestinal barrier dysfunction is a prevalent and varied manifestation of acute pancreatitis (AP). Molecular mechanisms underlying the early intestinal barrier in AP remain poorly understood.

To explore the biological processes and mechanisms of intestinal injury associated with AP, and to find potential targets for early prevention or treatment of intestinal barrier injury.

This study utilized single-cell RNA sequencing of the small intestine, alongside in vitro and in vivo experiments, to examine intestinal barrier function homeostasis during the early stages of AP and explore involved biological processes and potential mechanisms.

Seventeen major cell types and 33232 cells were identified across all samples, including normal, AP1 (4x caerulein injections, animals sacrificed 2 h after the last injection), and AP2 (8x caerulein injections, animals sacrificed 4 h after the last injection). An average of 980 genes per cell was found in the normal intestine, compared to 927 in the AP1 intestine and 1382 in the AP2 intestine. B cells, dendritic cells, mast cells (MCs), and monocytes in AP1 and AP2 showed reduced numbers compared to the normal intestine. Enterocytes, brush cells, enteroendocrine cells, and goblet cells maintained numbers similar to the normal intestine, while cytotoxic T cells and natural killer (NK) cells increased. Enterocytes in early AP exhibited elevated programmed cell death and intestinal barrier dysfunction but retained absorption capabilities. Cytotoxic T cells and NK cells showed enhanced pathogen-fighting abilities. Activated MCs, secreted chemokine (C-C motif) ligand 5 (CCL5), promoted neutrophil and macrophage infiltration and contributed to barrier dysfunction.

These findings enrich our understanding of biological processes and mechanisms in AP-associated intestinal injury, suggesting that CCL5 from MCs is a potential target for addressing dysfunction.

To construct a model of intestinal injury induced by radiotherapy for lung cancer and to study the protective effect and mechanism of isoliquiritigenin. The lungs of mice were irradiated with 0, 2, 4, 6, 8 Gy X-rays to screen the optimal radiation dose. A mouse model of lung cancer was established, and the tumor was irradiated once. At 3, 7, and 10 days after irradiation, H&E was used to detect the pathological manifestations of colon tissue in mice, and WB was used to detect the expression level of tight junction protein in colon tissue, so as to screen the best time point and study its possible mechanism. Molecular docking was used to study the tightness of isoliquiritigenin binding to TNF-α. Isoliquiritigenin (40 mg/kg) was given on the next day after 4 Gy X-ray irradiation. The levels of TNF-α and apoptosis, intestinal mucosal barrier function, MUC2 protein expression, and colon stem cell proliferation were detected. 4Gy X-ray local irradiation induced obvious colon injury in mice, and the injury was obvious on the 7th day. Isoliquiritigenin significantly improved the general condition, colonic histopathological changes, intestinal stem cell proliferation, and colonic tight junction function of lung cancer-bearing mice after radiotherapy. Further studies have found that isoliquiritigenin can downregulate the activation of TNF-α/Caspase-3 signaling pathway by inhibiting the expression of pro-inflammatory factor TNF-α, alleviate the apoptosis of colonic epithelial cells, improve the upregulation of colonic tight junction function, regulate the expression of MUC2, and promote the proliferation of intestinal stem cells, which may be related to the stable binding of isoliquiritigenin to TNF-α. Radiotherapy-induced bystander effect of lung cancer may be related to the abnormal expression of TNF-α. Isoliquiritigenin may downregulate the expression of TNF-α by binding to TNF-α, inhibit the apoptosis of colon cells, promote the proliferation of intestinal stem cells, and maintain the intestinal mucosal barrier to alleviate the colon injury induced by radiation bystander effect.

To examine the relationship between the Dietary Inflammatory Index (DII), abnormal bowel habits, and systemic serum inflammatory markers.

Data from 9,880 participants in the National Health and Nutrition Examination Survey (NHANES) 2005-2010 were analyzed. The DII was calculated from two 24-h dietary recalls. Bowel habits were assessed using the Bristol Stool Form Scale, and systemic inflammatory markers included AAPR, IBI, NLR, LMR, PNLR, LCR, LA, and PLR. Statistical analyses were performed using R, Zstats, and EmpowerStats to evaluate associations.

Higher DII scores were positively associated with abnormal bowel habits, including constipation [β (95% CI): 0.11 (0.01-0.22)] and diarrhea [β (95% CI): 0.42 (0.32-0.53)], and with PNLR [β (95% CI): 0.01 (0.01-0.01)], PNLRQ4 [β (95% CI): 0.13 (0.05-0.20)], IBI [β (95% CI): 0.02 (0.01-0.02)], and IBIQ4 [β (95% CI): 0.33 (0.25-0.42)] (p < 0.05). Negative associations were found with AAPR [β (95% CI): -0.33 (-0.60 - -0.06)] and AAPRQ4 [β (95% CI): -0.18 (-0.34 - -0.01)], while no significant associations were observed with LA, LCR, or LMR. Subgroup analyses confirmed stable associations between DII and both chronic diarrhea and constipation across seven subgroups. Smoothed curve fitting revealed nonlinear relationships. A J-shaped association between DII and chronic constipation was identified in BMI and IBI subgroups. For BMI >30, the breakpoint (K) was 1.89, with ORs of 1.228 (95% CI: 1.097-1.375) below and 3.318 (95% CI: 1.531-7.191) above this point. In the IBI Q4 subgroup, the breakpoint was 1.96, with ORs of 1.145 (95% CI: 1.013-1.294) below and 5.794 (95% CI: 2.359-14.228) above. In the diarrhea group, a U-shaped association was observed in the AAPR Q4 population, with a breakpoint of -1.312 and ORs of 0.657 (95% CI: 0.478-0.901) below and 1.266 (95% CI: 1.057-1.518) above.

Higher DII scores are linked to an increased risk of chronic constipation and diarrhea and are associated with systemic inflammatory markers and factors such as BMI.

Background: Hepatobiliary liver cancers (HBLCs) represent the sixth most common neoplasm in the world. Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) constitute the main HBLC types, with alarming epidemiological projections. Methods: In recent decades, alterations in gut microbiota, with mutual implications on the gut-liver axis and gut-biliary axis permeability status, have been massively investigated and proposed as HBLC pathogenetic deus ex machina. Results: In the HCC setting, elevated intestinal levels of Escherichia coli and other Gram-negative bacteria have been demonstrated, resulting in a close association with increased lipopolysaccharide (LPS) serum levels and, consequently, chronic systemic inflammation. In contrast, the intestinal microbiota of HCC individuals feature reduced levels of Lactobacillus spp., Bifidobacterium spp., and Enterococcus spp. In the CC setting, evidence has revealed an increased expression of Lactobacillus spp., with enhanced levels of Actynomices spp. and Alloscardovia spp. Besides impaired strains/species representation, gut-derived metabolites, including bile acids (BAs), short-chain fatty acids (SCFAs), and oxidative-stress-derived products, configure a network severely impacting the progression of HBLC. Conclusions: In the era of Precision Medicine, the clarification of microbiota composition and functioning in HCC and CC settings can contribute to the identification of individual signatures, potentially providing novel diagnostic markers, therapeutic approaches, and prognostic/predictive tools.

Nonsteroidal anti-inflammatory drug (NSAID) enteropathy is a serious clinical complication with no effective treatments available. Modulating the intestinal microbiota through dietary and nutritional targets is a promising strategy for preventing NSAID enteropathy. This study aimed to investigate the protective effect and underlying mechanisms of the probiotic Clostridium butyricum (CB) on indomethacin (IND)-induced enteropathy. C57BL/6J mice received CB treatment for 14 days along with concurrent IND gavage for the final 7 days. Caco2 cells were stimulated with IND to evaluate the effect of CB supernatant (CBS) on the intestinal barrier function, and LS174T cells were used to validate the modulatory action of CBS on the Notch signaling pathway. Our findings revealed that CB treatment prevented anorexia and weight loss, reduced the severity of enteropathy, and decreased the inflammatory response of the small intestine. CB also increased the expression of tight junction proteins and reduced permeability in mice and Caco2 cells. Additionally, CB suppressed apoptosis and promoted proliferation in the small intestine. Further research found that CB increased the number of goblet cells and MUC2 secretion. Mechanistically, CB may promote MUC2 secretion by suppressing the Notch signaling pathway, consistent with the results of intervention in LS174T cells with CBS. In conclusion, CB might prevent NSAID enteropathy by increasing MUC2 secretion through the inhibition of the Notch pathway. Our study identified the potential efficacy of CB as a preventive strategy against NSAID enteropathy and showed promising prospects for CB as a food supplement.

Irritable Bowel Syndrome (IBS) is a complex gastrointestinal disorder characterized by chronic abdominal pain and altered bowel habits, often linked to disruptions in intestinal barrier function. Increased intestinal permeability plays a key role in IBS pathogenesis, affecting immune responses, gut microbiota, and inflammation. This study conducts a bibliometric analysis to explore global research trends on intestinal permeability in IBS, focusing on key contributors, collaboration networks, and thematic shifts, particularly the interplay between the intestinal barrier, gut microbiota, and dietary components. A total of 411 articles were retrieved from Scopus, with 232 studies analyzed using Bibliometrix in R. To optimize screening, ASReview, a machine learning tool, was employed, utilizing the Naïve Bayes algorithm combined with Term Frequency-Inverse Document Frequency (TF-IDF) for adaptive ranking of articles by relevance. This approach significantly improved screening step efficacy. The analysis highlights growing research interest, with China and the USA as leading contributors. Key themes include the role of gut microbiota in modulating permeability, the impact of dietary components (fiber, probiotics, bioactive compounds) on tight junction integrity, and the exploration of therapeutic agents. Emerging studies suggest integrating gut barrier modulation with nutritional and microbiome-targeted strategies for IBS management. This study provides a comprehensive overview of research on intestinal permeability in IBS, mapping its evolution and identifying major trends. By highlighting key contributors and thematic areas, it offers insights to guide future investigations into the interplay between gut permeability, diet, and microbiota, advancing understanding of IBS pathophysiology and management.

Obesity is a prominent global health concern associated with chronic inflammation and metabolic disorders, such as insulin resistance, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD). Excessive consumption of saturated fats exacerbates these conditions by increasing intestinal barrier permeability and circulating endotoxins. This study aims to investigate, in a murine model of high-fat diet (HFD)-induced obesity, the potential beneficial effects of a grape pomace extract (GPE), rich in phenolic compounds, at mitigating endotoxemia, and liver steatosis. Underlying mechanisms were characterized in an in vitro model of intestinal inflammation and permeabilization, as induced by tumor necrosis factor alpha (TNFα) in Caco-2 cell monolayers. Consumption of a HFD (60% calories from fat) for 13 weeks induced obesity, insulin resistance, and liver damage, evidenced by higher levels of plasma alanine aminotransferase (ALT), hepatic triglycerides content, and steatosis. In addition, HFD caused metabolic endotoxemia, hepatic toll-like receptor 4 (TLR4) upregulation and inflammation. GPE supplementation significantly reduced body weight and subcutaneous and visceral adipose tissue weight, and attenuated metabolic dysregulation. Furthermore, GPE decreased circulating LPS levels and mitigated HFD-mediated hepatic TLR4 upregulation, nuclear factor kappa B (NF-κB) activation, and downstream expression of proteins involved in oxidative stress and inflammation (NOX4, TNFα, and F4/80). In Caco-2 cells, GPE mitigated TNFα-induced monolayer permeabilization, decreased tight junction (TJ) protein levels, enhanced cellular oxidant production, activated redox-sensitive signaling, i.e., NF-κB and ERK1/2, and increased NOX1 and MLCK mRNA levels, the latter being a key regulator of monolayer permeability. The above findings suggest that GPE may protect against HFD-induced obesity and associated metabolic dysfunction (insulin resistance and NAFLD) by modulating intestinal barrier integrity and related endotoxemia.

Chronic atrophic gastritis (CAG) is an important stage of precancerous lesions of gastric cancer. Effective treatment and regulation of CAG are essential to prevent its progression to malignancy. Traditional Chinese medicine (TCM) has shown multi-targeted efficacy in CAG treatment, with advantages in enhancing gastric mucosal barrier defense, improving microcirculation, modulating inflammatory and immune responses, and promoting lesion healing, etc. Clinical studies and meta-analyses indicate that TCM provides significant benefits, with specific Chinese herbal compounds and monomers demonstrating protective effects on the gastric mucosa through mechanisms including anti-inflammation, anti-oxidation, and regulation of cellular proliferation and apoptosis, etc. Finally, it is pointed out that the efficacy of TCM in the treatment of CAG requires standardized research and unified standards, and constantly clarifies and improves the evaluation criteria of each dimension of gastric mucosal barrier function.

This study investigated the protective effects and mechanisms of cow placenta peptides (CPP) on intestinal barrier damage in aging model mice. Forty-eight male ICR mice were assigned to four groups: a control group (N), an aging model group (M), a CPP treatment group (T), and a vitamin C treatment group (P). Groups T and P received oral administration of CPP (2000 mg/kg/day) and vitamin C (100 mg/kg/day), respectively, while groups M, T, and P were subjected to intraperitoneal injections of D-galactose (D-gal) (300 mg/kg/day). Group N received an equivalent volume of normal saline via intraperitoneal injection. Treatments were administered once daily for 8 weeks. The results demonstrated that CPP significantly alleviated D-galactose-induced intestinal structural damage, increasing the villus height-to-crypt depth ratio and reducing serum diamine oxidase (DAO) and lipopolysaccharide (LPS) levels. CPP notably alleviated intestinal oxidative stress and inflammation, restored tight junction expression, and enhanced intestinal barrier integrity. Transcriptome sequencing identified 1396 DEGs associated with CPP's effects, highlighting TLR4, IL-1β, and Mmp9 as core regulatory genes through protein-protein interaction network analysis. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses implicated the TLR4/NF-κB signaling pathway, which was further validated. Western blotting confirmed that CPP significantly down-regulated TLR4, IKKβ, and p-NF-κB p65 protein expression in the intestines of aging mice. In conclusion, CPP effectively alleviates D-gal-induced intestinal barrier damage in aging mice by enhancing antioxidant defense and inhibiting the TLR4/NF-κB signaling pathway, thereby diminishing inflammation and protecting intestinal barrier integrity.

Inflammatory bowel disease (IBD) is characterized by the upregulation of reactive oxygen species (ROS) and dysfunction of gut immune system, and microbiota. The conventional treatments mainly focus on symptom control with medication by overuse of drugs. There is an urgent need to develop a closed-loop strategy that combines in situ monitoring and precise treatment. Herein, we innovatively designed the 'cluster munition structure' theranostic microgels to realize the monitoring and therapy for ulcerative colitis (a subtype of IBD). The superoxide anion specific probe (tetraphenylethylene-coelenterazine, TPC) and ROS-responsive nanogels consisting of postbiotics urolithin A (UA) were loaded into alginate and ion-crosslinked to obtain the theranostic microgels. The theranostic microgels could be delivered to the inflammatory site, where the environment-triggered breakup of the microgels and release of the nanogels were achieved in sequence. The TPC-UA group had optimal results in reducing inflammation, repairing colonic epithelial tissue, and remodeling microbiota, leading to inflammation amelioration and recovery of tight junction between the colonic epithelium, and maintenance of gut microbiota. During the recovery process, the local chemiluminescence intensity, which is proportional to the degree of inflammation, was gradually inhibited. The cluster munition of theranostic microgels displayed promising outcomes in monitoring inflammation and precise therapy, and demonstrated the potential for inflammatory disease management.

Intestinal barrier function lies at a critical interface of a range of peripheral and central processes that influence disorders of gut-brain interactions (DGBI). Although rigorously tested, the role of barrier dysfunction in driving clinical phenotype of DGBI remains to be fully elucidated. In vitro, in vivo, and ex vivo strategies can test various aspects of the broader permeability and barrier mechanisms in the gut. Luminal mediators of host, bacterial, and dietary origin can influence the barrier function and a disrupted barrier can also influence the luminal milieu. Critical to our understanding is how barrier dysfunction is influenced by stress and other comorbidities that associate with DGBI and the crosstalk between barrier and neural, hormonal, and immune responses. Additionally, the microbiome's significant role in the communication between the brain and gut has led to the integrative model of a microbiome gut-brain axis with reciprocal interactions between brain networks and networks composed of multiple cells in the gut, including immune cells, enterochromaffin cells, gut microbiota and the derived luminal mediators. This review highlights the techniques for assessment of barrier function, appraises evidence for barrier dysfunction in DGBI including mechanistic studies in humans, as well as provides an overview of therapeutic strategies that can be used to directly or indirectly restore barrier function in DGBI patients.

Disorders of Gut-Brain Interaction (DGBI) are widely prevalent and commonly encountered in gastroenterology practice. While several peripheral and central mechanisms have been implicated in the pathogenesis of DGBI, a recent body of work suggests an important role for the gut microbiome. In this review, we highlight how gut microbiota and their metabolites affect physiologic changes underlying symptoms in DGBI, with a particular focus on their mechanistic influence on GI transit, visceral sensitivity, intestinal barrier function and secretion, and CNS processing. This review emphasizes the complexity of local and distant effects of microbial metabolites on physiological function, influenced by factors such as metabolite concentration, duration of metabolite exposure, receptor location, host genetics, and underlying disease state. Large-scale in vitro work has elucidated interactions between host receptors and the microbial metabolome but there is a need for future research to integrate such preclinical findings with clinical studies. The development of novel, targeted therapeutic strategies for DGBI hinges on a deeper understanding of these metabolite-host interactions, offering exciting possibilities for the future of treatment of DGBI.

Chronic stress and orthodontic treatment have been revealed to trigger systemic stress responses in rats. This study aimed to investigate the effects of restraint stress and orthodontic treatment on the intestinal epithelial structure, barrier function, flora, and metabolism in rats. Twenty 8-week-old male Wistar rats were randomly divided into four groups: sham-stressed non-orthodontic (CC), sham-stressed orthodontic (CO), stressed non-orthodontic (SC), and stressed orthodontic (SO). The stress intervention involved subjecting the rats to restraint stress for 21 days, while the orthodontic intervention consisted of maxillary first molar traction from days 8 to 21. Histological and immunohistochemical staining were used to observe the epithelial structure and barrier function of the colon. The intestinal flora and metabolite alterations were investigated by 16S rRNA high-throughput sequencing and untargeted metabolomics sequencing. Colonic epithelial tissue disruption, mucus cells reduction, and a decreased expression of intestinal tight junction proteins were observed in the CO, SC, and SO groups. Lactobacillus spp. abundance was significantly lower in the CO group than in the CC group. Prevotella spp. abundance was significantly lower in the SC and SO groups than in the CC and CO groups. The differential metabolite enrichment pathways between each inter-group comparison might all be related to amino acid biosynthesis, protein digestion and absorption, and cofactor biosynthesis. Both restraint stress and orthodontic treatment may adversely affect the colonic epithelial structure and barrier function of rats. The intestinal flora structure and types of metabolites were also affected cumulatively.

The human gut microbiota, consisting of trillions of microorganisms, plays a crucial role in gastrointestinal (GI) health and disease. Dysbiosis, an imbalance in microbial composition, has been linked to a range of GI disorders, including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease, and colorectal cancer. These conditions are influenced by the interactions between the gut microbiota, the host immune system, and the gut-brain axis. Recent research has highlighted the potential for microbiome-based therapeutic strategies, such as probiotics, prebiotics, fecal microbiota transplantation (FMT), and dietary modifications, to restore microbial balance and alleviate disease symptoms. This review examines the role of gut microbiota in the pathogenesis of common gastrointestinal diseases and explores emerging therapeutic approaches aimed at modulating the microbiome. We discuss the scientific foundations of these interventions, their clinical effectiveness, and the challenges in their implementation. The review underscores the therapeutic potential of microbiome-targeted treatments as a novel approach to managing GI disorders, offering personalized and alternative options to conventional therapies. As research in this field continues to evolve, microbiome-based interventions hold promise for improving the treatment and prevention of gastrointestinal diseases.