Since the description of postinfection irritable bowel syndrome (IBS), a role for gut microbes in the pathogenesis of IBS has been proposed. Molecular microbiological tools have now been applied to IBS, though data are largely derived from fecal samples with attendant limitations. Metagenomics, metabolomics, and other 'omics facilitate a comprehensive picture of the microbiome and its metabolic activity. Has a microbial signature characteristic of IBS been identified? The answer is no; this should not be a surprise given the heterogeneity of the phenotype and each individual's microbiome profile.

Diabetes has become a global health crisis, affecting over 800 million people, with serious complications such as vascular and neurological damage. While diabetes management has been extensively studied, the impact of environmental pollutants, particularly microplastics (PS), on diabetic health remains poorly understood. PS, defined as plastic particles smaller than 5 mm, are pervasive and can enter the body through inhalation or ingestion, posing potential risks. However, the effects of PS exposure, particularly in diabetes, have not been adequately explored. Most studies focus on high-concentration, long-term exposure, which does not reflect typical human exposure levels. This study investigates the effects of short-term PS exposure on diabetic SD rats, using histological, apoptotic, and omics techniques, including metabolomics, lipidomics, and 16S rDNA sequencing. Our results show that short-term PS exposure exacerbates lung and intestinal damage in diabetic rats, with significant alterations in the gut microbiome. We also observed correlations between differential metabolites and microbiota changes. These findings provide novel evidence that short-term PS exposure, at concentrations reflecting daily contact, worsens metabolic dysfunction and intestinal dysbiosis in diabetes. This study emphasizes the need to consider environmental pollutants in diabetes management and highlights potential strategies for prevention and therapy.

Breath testing to diagnose intestinal microbial overgrowth (MO) is being increasingly utilized, in part due to direct-to-consumer testing modalities. However, the concept of breath testing in the diagnosis of MO is controversial due to numerous limitations regarding optimal substrate, diagnostic thresholds, and confounding variables. We provide seven real-world cases which comprehensively illustrate the principles and nuances of the interpretation of breath testing.

We highlight recent studies which examine the optimal substrate for breath testing (glucose versus lactulose), the subtypes and clinical significance of breath test patterns including hydrogen, methane, and hydrogen-sulfide, elevated baseline gas levels, and confounders to breath test interpretation including transit time and diet. Reviewing the latest evidence, we provide recommendations for a personalized interpretation of breath tests utilizing unique patient factors. We conclude with an algorithm to assist clinicians in providing more accurate diagnoses.

Small intestinal bacterial overgrowth (SIBO) is a functional digestive disorder whose incidence has been acknowledged by several medical associations, such as the American Gastroenterological Association. It is estimated that between 14% and 40% of patients diagnosed with irritable bowel syndrome also have SIBO, highlighting the importance of accurate diagnosis to enable effective treatment plans. Nutrition and diet therapy play a pivotal role in SIBO management, not only in alleviating symptoms but also in preventing relapses. The objective of this review is to gather updated information on dietary management for SIBO to define the role of the dietitian and determine the most suitable nutritional therapy based on scientific evidence. The review will encompass various strategies, ranging from specific diets to dietary supplements, as well as the potential contribution of dietary treatment to improving SIBO.

Food-as-medicine (FAM) is an emerging trend among medical doctors, health insurers, startups, and governmental public-health and nongovernmental organizations. FAM implies using food as a part of an individual's health plan to prevent or help treat acute and chronic health conditions and diseases. We highlight trends and hurdles in the FAM intervention pyramid. Our viewpoint is to indicate how interventions might change the future demand for specific food groups, their transport in supply chains, and the technologies used to process them. On the basis of national guidelines, dietary interventions can help to prevent and treat many diseases, including cardiovascular disease, cancers, type 2 diabetes, and obesity. FAM R&D and services offer more individualized treatments. This is challenging given the interindividual variability and complexity of the body's response to food and related factors, such as dietary habits, genetics, lifestyle, and biosphere. Quantifying health improvements is essential to prove the added value of more individualized FAM interventions compared with adopting a general healthy diet. It is unclear which level of individualization of interventions produces the largest health benefits at the lowest costs for the patient, healthcare system, and climate. FAM interventions can support and complement conventional medical treatment. They will require a shift to producing more health-promoting foods, including whole foods, minimally processed foods, and selected processed foods. The food processing industry and supply chains must adapt to these new scenarios. Auxiliary technologies and methods are enablers, including delivery services, wearable technology, health-monitoring apps, and data-driven consumer behavior analysis.

Functional dyspepsia is common and classified as a disorder of gut-brain interaction (DGBI). The prevalence is estimated around 10 % of the population. Diagnosis is based on symptoms, which are based on the Rome IV criteria, in combination with diagnostic procedures that may include laboratory testing, Helicobacter pylori testing, upper gastrointestinal endoscopy, abdominal ultrasound, and other examinations, depending on the severity, duration and presence of alarming symptoms. Therapeutic procedures include psychoeducation, dietary counseling, mind-body procedures, psychotherapy and medication. The S1 guideline summarizes the current state of knowledge and allows a targeted approach based on the currently available medical evidence.

To explore the efficacy and mechanism of Pomegranate peel Ginger ultrafine powder (PG) in treating chronic enteritis in mice. Sixty SPF-grade mice were randomly divided into a blank group, a model group, loperamide hydrochloride group (5 mg/kg), a high-dose PG group (100 mg/kg), a medium-dose group (50 mg/kg), and a low-dose group (25 mg/kg), with 10 mice in each group and an equal number of males and females. A chronic enteritis mouse model was established using a multifactorial method of low temperature + ice water + castor oil. The blank group was given an equal amount of physiological saline intragastrically, while the other groups were intervened with corresponding drugs for 7 consecutive days. After 7 days, samples were collected, and Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of interleuckin 1β (IL-1β), IL-6, and Tumor necrosis factorα(TNF-α) in mouse serum. HE staining was used to examine the pathological changes in the small intestine. oxidative reagent kits were used to detect the content of total superoxide dismutase(T-SOD) and Malondialdehyde (MDA) in the small intestine. Western blot was used to detect the expression of Aquaporin 8(AQP8) proteins in the small intestine. Real time quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to detect the expression of AQP3, AQP4, AQP8, and Sodium/hydrogen exchanger 8 (NHE8) genes in the small intestine. metagenomics was used to detect the gut microbiota in mouse feces. Compared with the model group, all doses of PG groups reduced the levels of IL-1β, IL-6, and TNF-α in mouse serum (P<0.05), improved pathological changes in the small intestine, increased the content of T-SOD in the small intestine tissue, reduced the content of MDA, increased the expression of AQP4 and AQP8 mRNA, and decreased the expression of AQP3 and NHE8 mRNA (P<0.05), increased the expression of AQP8 protein. PG could improve the pathological changes of chronic enteritis in mice, enhance antioxidant capacity, and alleviate diarrhea caused by chronic enteritis by downregulating the expression of intestinal epithelial transport proteins and acute-phase proteins, and altering gut microbiota.

Non-communicable diseases (NCDs), such as type 2 diabetes (T2D) and metabolic dysfunction-associated fatty liver disease, have reached epidemic proportions worldwide. The global increase in dietary sugar consumption, which is largely attributed to the production and widespread use of cheap alternatives such as high-fructose corn syrup, is a major driving factor of NCDs. Therefore, a comprehensive understanding of sugar metabolism and its impact on host health is imperative to rise to the challenge of reducing NCDs. Notably, fructose appears to exert more pronounced deleterious effects than glucose, as hepatic fructose metabolism induces de novo lipogenesis and insulin resistance through distinct mechanisms. Furthermore, recent studies have demonstrated an intricate relationship between sugar metabolism and the small intestinal microbiota (SIM). In contrast to the beneficial role of colonic microbiota in complex carbohydrate metabolism, sugar metabolism by the SIM appears to be less beneficial to the host as it can generate toxic metabolites. These fermentation products can serve as a substrate for fatty acid synthesis, imposing negative health effects on the host. Nevertheless, due to the challenging accessibility of the small intestine, our knowledge of the SIM and its involvement in sugar metabolism remains limited. This review presents an overview of the current knowledge in this field along with implications for future research, ultimately offering potential therapeutic avenues for addressing NCDs.

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.

Functional dyspepsia (FD) is a prevalent functional gastrointestinal disorder associated with oxidative stress (OS) and dysbiosis. Chaihushugan powder (CHSGP) demonstrates efficacy in treating FD; however, the underlying therapeutic mechanism is not yet elucidated. This study aims to investigate the effects of CHSGP on OS and gut microbiota (GM) in FD rats, with a particular emphasis on the role of GM as a potential target for the antioxidant properties of CHSGP.

The FD rat model was established with a modified tail-clamp stimulation and the administration of the CHSGP decoction at a dosage of 9.6 g/kg via gavage for a duration of 4 weeks. The GM was depleted by the administration of a cocktail of metronidazole (200 mg/kg), ampicillin (200 mg/kg), neomycin sulfate (200 mg/kg), and vancomycin (100 mg/kg). Fecal microbiota transplantation (FMT) was performed with CHSGP-treated fecal supernatant at a dosage of 10 mL/kg. The gastrointestinal motility was measured using the rates of gastric emptying and small intestine propulsion. Hematoxylin and eosin staining was employed to elucidate the pathological changes, while the transmission electron microscope was used to examine the microstructures of the interstitial cells of Cajal (ICC). Chemiluminescence, colorimetric assay, immunofluorescence co-staining, and western blot assay were employed to identify the OS-related markers (ROS, SOD, NOX4, PRDX1, and TRX2). Sequencing of fecal microbiota was performed utilizing 16S rDNA.

The CHSGP decoction promoted gastrointestinal motility, protected the microstructure of ICC, and reduced OS in FD rats. The GM composition was also regulated by CHSGP. However, these effects disappeared after microbiota depletion. Fortunately, the FMT therapy reinstated them.

Chaihushugan powder decoction might regulate the GM to alleviate mitochondrial OS in the gastric tissues of FD rats.

Dysbiosis is a clinical condition marked by altered gut microbiota resulting from external and internal host factors. It is strongly associated with gastrointestinal and extraintestinal alterations, so its symptomatology is broad and nonspecific. To date, gaps remain that limit professionals from making a timely diagnosis and prescribing the appropriate treatment. We aim to synthesize existing literature regarding clinical parameters for the early detection of patients with intestinal dysbiosis and the clinical events in which the use of probiotics as adjuvant therapy is most frequently reported. A scoping review of the literature was conducted in PubMed, Embase, Cochrane, and BVS (Biblioteca Virtual en Salud in Spanish) databases for articles published in the last 5 years. Primary studies and literature reviews related to clinical presentation, dysbiosis screening, and probiotics as adjuvant therapy for adult and pediatric patients were included. Twenty-three articles were retrieved in which the most frequently reported symptoms were abdominal distension, abdominal pain, and diarrhea. Chronic and metabolic diseases where the conditions most strongly associated with dysbiosis. Depending on symptomatology and etiology, dysbiosis is often treated with probiotics. Dysbiosis, often linked to diarrhea, should be considered with other symptoms like abdominal distension and pain, along with predisposing conditions and patient risk factors. Probiotics are commonly used as co-adjuvant treatments for antibiotic-associated diarrhea, irritable bowel syndrome, and childhood allergic diseases. The most commonly used probiotics were Weizmannia coagulans (formerly B. coagulans), Alkalihalobacillus clausii (formerly Bacillus clausii), Lacticaseibacillus rhamnosus, Limosilactobacillus reuteri, and Saccharomyces boulardii.

The recognition and treatment of intestinal bacterial overgrowth syndrome are matters of controversy. The symptoms that have guided the search for the disorder suffer from lack of specificity, especially in the absence of well-defined predisposing factors. The accuracy of diagnostic procedures has been questioned and the proposed therapies achieve generally low effectiveness figures, with large differences between available studies. It is also unknown whether the normalization of tests is really a guarantee of cure. Within this framework of uncertainty, and in order to contribute to the guidance and homogenization of medical practice, a group of experts from the AEG and ASENEM have formulated the key questions on the management of this pathology and have provided answers to them, in accordance with the available scientific evidence. In addition, they have drawn up statements based on the conclusions of the review and have voted on them individually to reflect the degree of consensus for each statement.

Digestive disorders of gut-brain interaction (DGBI) are very common, predominant in females, and usually associated with intestinal barrier dysfunction, dysbiosis, and stress. We previously found that females have increased susceptibility to intestinal barrier dysfunction in response to acute stress. However, whether this is associated with changes in the small bowel microbiota remains unknown. We have evaluated changes in the small intestinal microbiota in response to acute stress to better understand stress-induced intestinal barrier dysfunction.

Jejunal biopsies were obtained at baseline and 90 min after cold pain or sham stress. Autonomic (blood pressure and heart rate), hormonal (plasma cortisol and adrenocorticotropic hormone) and psychological (Subjective Stress Rating Scale) responses to cold pain and sham stress were monitored. Microbial DNA from the biopsies was analyzed using a 16S metabarcoding approach before and after cold pain stress and sham stress. Differences in diversity and relative abundance of microbial taxa were examined.

Cold pain stress was associated with a significant decrease in alpha diversity (P = 0.015), which was more pronounced in females, along with significant sex differences in the abundance of specific taxa and the overall microbiota composition. Microbiota alterations significantly correlated with changes in psychological responses, hormones, and gene expression in the intestinal mucosal. Cold pain stress was also associated with activation of autonomic, hormonal and psychological response, with no differences between sexes.

Acute stress elicits rapid alterations in bacterial composition in the jejunum of healthy subjects and these changes are more pronounced in females. Our results may contribute to the understanding of female predominance in DGBI.

The small intestinal microbiota has a crucial role in gastrointestinal health, affecting digestion, immune function, bile acid homeostasis and nutrient metabolism. The challenges of accessibility at this site mean that our knowledge of the small intestinal microbiota is less developed than of the colonic or faecal microbiota. Here, we summarize the features and fluctuations of the microbiota along the small intestinal tract, focusing on humans, and discuss physicochemical factors and assessment methods, including the technical challenges of investigating the low microbial biomass of the proximal small bowel. We highlight the essential protective mechanisms of the small intestine, including motility, the paracellular barrier and mucus, and secretory immunity, to show their roles in limiting excessive exposure of host tissues to microbial metabolites. We address current knowledge gaps, particularly the variability among individuals, the effects of dysbiosis of the small intestinal microbiota on health and how different taxa in small intestinal microbiota could compensate for each other functionally.

Social and economic factors, such as food insecurity, contribute to long coronavirus disease (COVID). During the pandemic, a significant rise in food insecurity was observed, both in Brazil and worldwide. We aimed to investigate the association between food insecurity and long COVID in Brazilian adults.

Cross-sectional study nested within the Prospective study About Mental and Physical Health in Adults (PAMPA) Cohort. Participants completed an online questionnaire in June 2022. We assessed food insecurity using the Brazilian Scale of Food Insecurity. Long COVID was defined as any post-coronavirus disease 2019 symptoms that persisted for at least 3 months after infection.

A total of 956 participants were included (74.0% female, median age 36 (Interquartile Range [IQR] (29-45.7). The prevalence of food insecurity was 29.4%, and 77.8% had long COVID. Food insecurity was associated with an increased probability of long COVID (prevalence ratio [PR]: 1.15, 95% confidence interval [CI]: 1.08-1.22). Participants in food insecurity situations had a higher likelihood of experiencing neurological (PR: 1.19, 95% CI: 1.10-1.28), pulmonary (PR: 1.33, 95% CI: 1.17-1.52) and gastrointestinal (PR: 1.57, 95% CI: 1.31-1.88) symptoms after infection.

Food insecurity was associated with long COVID. Governments must plan public policies to mitigate the effects of long COVID and food insecurity.

Irritable bowel syndrome (IBS) and small intestinal bacterial overgrowth (SIBO) share similar abdominal symptoms; however, their differentiation remains controversial.

To illustrate the differences between the two conditions.

Patients and healthy controls completed questionnaires and provided stool samples for analysis.

IBS presented with the most severe symptoms and was specifically characterized by intense abdominal pain and frequent episodes of diarrhea. Patients with IBS displayed more dysregulated taxonomy within the fecal microbiota than SIBO. Opportunistic pathogens, including Lachnoclostridium, Escherichia-Shigella, and Enterobacter were enriched in the IBS group which contributed to increased bacterial pathogenicity and positively correlated with abdominal pain and bloating, meanwhile, Lachnoclostridium and Escherichia-Shigella were found to be associated with metabolites affiliated to bile acids, alcohols and derivatives. Bacteria enriched in SIBO group correlated with constipation. The bacterial co-occurrence network within the SIBO group was the most intricate. Ruminococcaceae Group were defined as core bacteria in SIBO. Differential metabolites affiliated to androstane steroids and phenylacetic acids were associated with core bacteria.

Our study elucidates the differences between IBS and SIBO in terms of symptoms, microbiota and functions, which provides insights into a better understanding of both diseases and evidence for different treatment strategies.

Breath testing for small intestinal bacterial overgrowth (SIBO) is typically performed using clinic-based equipment or single-use test kits.

This study aimed to evaluate the utility of a portable, point-of-care breath analysis device (AIRE®, FoodMarble) in patients suspected to have SIBO. A technical assessment including a comparison to existing mail-in kits was first performed. Then, postprandial breath hydrogen levels of patients before and after antibiotic treatment were gathered and compared to levels seen in a healthy cohort.

For the comparison, 50 patients suspected of having SIBO were provided with an AIRE device and performed concurrent LHBTs at-home with a mail-in breath test kit. For the postprandial analysis, twenty-four patients with chronic GI symptoms measured their postprandial hydrogen for 7 days prior to antibiotic treatment and for 7 days after treatment. 10 healthy controls also measured their postprandial hydrogen for 7 days.

Substantial agreement was demonstrated between AIRE and the mail-in kits for the performance of lactulose hydrogen breath tests (κ = 0.8). Prior to treatment, patients had significantly greater daily postprandial hydrogen than healthy controls (p < 0.001). The mean postprandial hydrogen of patients reduced significantly after treatment (p < 0.001).

Measuring postprandial hydrogen shows potential as a means of differentiating patients with chronic GI symptoms from healthy controls and may be useful in monitoring patients before, during, and after treatment. Future studies could help determine if pre-treatment breath gas levels are predictive of response to antibiotic treatment.

Irritable bowel syndrome (IBS) is a chronic disorder with an important impact on patients' quality of life. Although several data indicate that psychological symptoms are frequently reported by patients with IBS, few therapies have been evaluated regarding these issues.

A retrospective observational study was conducted to evaluate the effectiveness of a probiotic-based dietary supplement (Colicron®) in a group of patients with diarrhea-predominant IBS (IBS-D). We included patients treated with Colicron® (1 cps/day for 8 weeks). Primary endpoint was the gastrointestinal symptoms' remission evaluated by Visual Analogue Scale (VAS); secondary endpoint was the impact of the treatment on physical and mental health evaluated by Hospital Anxiety and Depression Score (HADS) and Short Form Health Survey 36 (SF-36). VAS was assessed at week 4 (T4), week 8 (T8) and week 12 (T12), whereas HADS and SF-36 were performed even at the start of the Colicron® treatment (T0).

An improvement of VAS Score was observed at T8 (P<0.001) and T12 (P<0.05) compared to T4. Lower HADS-A (anxiety subdomain) score was obtained at each time point versus T0 (P<0.01), and higher scores of all SF-36 domains were observed during the treatment (0.05

CONCLUSIONS

Colicron® could be useful in improving both gastrointestinal and psychological symptoms in IBS-D patients. Further prospective clinical trials are needed to confirm these preliminary data.

Collapse

Beside the respiratory tract, the skin and the gut represent the first defensive lines of our body against the external insults displaying many important biochemical features able to maintain the epithelial barrier integrity and to regulate the tissue immune responses. The human microbiome is essential in maintaining the tissue homeostasis and its dysregulation may lead to tissue conditions including inflammatory pathologies. Among all external insults, air pollutants have been shown to cause oxidative stress damage within the target tissues via an OxInflammatory response. Dysregulation of the gut microbiome (dysbiosis) by outdoor stressors, including air pollutants, may promote the exacerbation of the skin tissue damage via the interplay between the gut-skin axis. The intent of this review is to highlight the ability of exogenous stressors to modulate the human gut-skin axis via a redox regulated mechanism affecting the microbiome and therefore contributing to the development and aggravation of gut and skin conditions.

Antibiotics are safe, effective drugs and continue to save millions of lives and prevent long-term illness worldwide. A large body of epidemiological, interventional and experimental evidence shows that exposure to antibiotics has long-term negative effects on human health. We reviewed the literature data on the links between antibiotic exposure, gut dysbiosis, and chronic disease (notably with regard to the "developmental origins of health and disease" ("DOHaD") approach). Molecular biology studies show that the systemic administration of antibiotic to infants has a rapid onset but also often a long-lasting impact on the microbial composition of the gut. Along with other environmental factors (e.g., an unhealthy "Western" diet and sedentary behavior), antibiotics induce gut dysbiosis, which can be defined as the disruption of a previously stable, functionally complete microbiota. Gut dysbiosis many harmful long-term effects on health. Associations between early-life exposure to antibiotics have been reported for chronic diseases, including inflammatory bowel disease, celiac disease, some cancers, metabolic diseases (obesity and type 2 diabetes), allergic diseases, autoimmune disorders, atherosclerosis, arthritis, and neurodevelopmental, neurodegenerative and other neurological diseases. In mechanistic terms, gut dysbiosis influences chronic disease through direct effects on mucosal immune and inflammatory pathways, plus a wide array of direct or indirect effects of short-chain fatty acids, the enteric nervous system, peristaltic motility, the production of hormones and neurotransmitters, and the loss of intestinal barrier integrity (notably with leakage of the pro-inflammatory endotoxin lipopolysaccharide into the circulation). To mitigate dysbiosis, the administration of probiotics in patients with chronic disease is often (but not always) associated with positive effects on clinical markers (e.g., disease scores) and biomarkers of inflammation and immune activation. Meta-analyses are complicated by differences in probiotic composition, dose level, and treatment duration, and large, randomized, controlled clinical trials are lacking in many disease areas. In view of the critical importance of deciding whether or not to prescribe antibiotics (especially to children), we suggest that the DOHaD concept can be logically extended to "gastrointestinal origins of health and disease" ("GOHaD") or even "microbiotic origins of health and disease" ("MOHaD").

Glucose (GBT) and lactulose (LBT) breath tests have been recommended for the diagnosis of small intestinal bacterial overgrowth (SIBO). LBT may yield a higher prevalence of SIBO diagnosis, because of its limited small bowel absorption, and therefore colonic fermentation. The aim of this retrospective study was to confirm this hypothesis, in irritable bowel syndrome patients (IBS).

Among a cohort of 995 patients who underwent GBT or LBT, 287 with typical IBS according to Rome IV criteria, without past digestive surgery or significant medical comorbidities, were included.

155 IBS patients underwent GBT, and 132 LBT (71% women, mean age 45±15, mean BMI: 22.6±4.3 kg/m2). There were no difference between both groups in terms of demographics, IBS type and severity of symptoms. The prevalence of SIBO according to LBT was 47%, versus 4.5% only with GBT (p<0.001). The prevalence of methane values ≥ 10 ppm were similar in both groups (34%).

LBT is very frequently positive in IBS patients, as compared to GBT. The 2 tests are thus not interchangeable for the diagnosis of SIBO. Furthermore, the positivity of both tests was not correlated with symptoms, which may indicate a poor clinical interest of these tests in IBS.

Small intestinal bacterial overgrowth (SIBO) is a clinical entity recognized since ancient times; it represents the consequences of bacterial overgrowth in the small intestine associated with malabsorption. Recently, SIBO as a term has been popularized due to its high prevalence reported in various pathologies since the moment it is indirectly diagnosed with exhaled air tests. In the present article, the results of duodenal/jejunal aspirate culture testing as a reference diagnostic method, as well as the characteristics of the small intestinal microbiota described by culture-dependent and culture-independent techniques in SIBO, and their comparison with exhaled air testing are presented to argue about its overdiagnosis.

The intestine is populated by a complex and dynamic assortment of microbes, collectively called gut microbiota, that interact with the host and contribute to its metabolism and physiology. Diet is considered a key regulator of intestinal microbiota, as ingested nutrients interact with and shape the resident microbiota composition. Furthermore, recent studies underscore the interplay of dietary and microbiota-derived nutrients, which directly impinge on intestinal stem cells regulating their turnover to ensure a healthy gut barrier. Although advanced sequencing methodologies have allowed the characterization of the human gut microbiome, mechanistic studies assessing diet-microbiota-host interactions depend on the use of genetically tractable models, such as Drosophila melanogaster. In this review, we first discuss the similarities between the human and fly intestines and then we focus on the effects of diet and microbiota on nutrient-sensing signaling cascades controlling intestinal stem cell self-renewal and differentiation, as well as disease. Finally, we underline the use of the Drosophila model in assessing the role of microbiota in gut-related pathologies and in understanding the mechanisms that mediate different whole-body manifestations of gut dysfunction.

The small intestinal microbiota (SIM) is essential for gastrointestinal health, influencing digestion, immune modulation, and nutrient metabolism. Unlike the colonic microbiota, the SIM has been poorly characterized due to sampling challenges and ethical considerations. Current evidence suggests that the SIM consists of five core genera and additional segment-specific taxa. These bacteria closely interact with the human host, regulating nutrient absorption and metabolism. Recent work suggests the presence of two forms of small intestinal bacterial overgrowth, one dominated by oral bacteria (SIOBO) and a second dominated by coliform bacteria. Less invasive sampling techniques, omics approaches, and mechanistic studies will allow a more comprehensive understanding of the SIM, paving the way for interventions engineering the SIM towards better health.

Defining what constitutes a healthy microbiome throughout our lives remains an ongoing challenge. Understanding to what extent host and environmental factors can influence it has been the primary motivation for large population studies worldwide. Here, we describe the fecal microbiome of 3,746 individuals (0-87 years of age) in a nationwide study in the Netherlands, in association with extensive questionnaires. We validate previous findings, such as infant-adult trajectories, and explore the collective impact of our variables, which explain over 40% of the variation in microbiome composition. We identify associations with less explored factors, particularly those ethnic related, which show the largest impact on the adult microbiome composition, diversity, metabolic profiles, and CAZy (carbohydrate-active enzyme) repertoires. Understanding the sources of microbiome variability is crucial, given its potential as a modifiable target with therapeutic possibilities. With this work, we aim to serve as a foundational element for the design of health interventions and fundamental research.

Evodiamine (EVO) is one of the primary components of Evodia rutaecarpa and has been found to have a positive therapeutic effect on various digestive system diseases. However, no systematic review has been conducted on the research progress and mechanisms of EVO in relation to digestive system diseases, and its toxicity.

This study aimed to provide a reference for future research in this field.

A systematic review and meta-analysis of the research progress, mechanisms, and toxicity of EVO in the treatment of digestive system diseases.

Five electronic databases were utilized to search for relevant experiments. We conducted a comprehensive review and meta-analysis of the pertinent literature following the guidelines of Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA).

EVO's animal experiments in digestive system diseases primarily focus on colorectal cancer, gastric ulcers, liver cancer, liver fibrosis, ulcerative colitis, colitis-associated cancer, and functional gastrointestinal disorders. EVO also has positive effects on pancreatic cancer, radiation enteritis, gastric cancer, tongue squamous cancer, hepatitis B, oral cancer, and esophageal cancer in vivo. EVO's in cellular experiments primarily focus on SGC7901, HT29, HCT-116, and HepG2 cells. EVO also exhibits positive effects on SW480, LoVo, BGC-823, AGS, COLO-205, MKN45, SMMC-7721, Bel-7402, QGY7-701, PANC-1, SW1990, BxPC-3, HSC4, MC3, HONE1, and CNE1 cells in vitro. The potential common pathways include TGF-β, PI3K-AKT, Wnt, ErbB, mTOR, MAPK, HIF-1, NOD-like receptor, NF-κB, VEGF, JAK-STAT, AMPK, Toll-like receptor, EGFR, Ras, TNF, AGE-RAGE, Relaxin, FoxO, IL-17, Hippo, and cAMP. The mechanisms of EVO on ulcerative colitis, gastric cancer, and HCT116 cells are still controversial in vivo. EVO may have a bidirectional regulatory effect on functional gastrointestinal disorders through calcium signaling. The mechanisms of EVO on HCT116, HT29, SW480, AGS, COLO-205, and SW1990 cells are still controversial in vitro. The question of whether EVO has obvious toxicity is controversial.

In both cellular and animal experiments, EVO has demonstrated positive impacts on digestive system diseases. Nevertheless, additional in vivo and in vitro research is required to confirm the beneficial effects and mechanisms of EVO on digestive system diseases, as well as its potential toxicity.

Bile acids (BAs) play a crucial role in the human body's defense against infections caused by bacteria, fungi, and viruses. BAs counteract infections not only through interactions with intestinal bacteria exhibiting bile salt hydrolase (BSH) activity but they also directly combat infections. Building upon our research group's previous discoveries highlighting the role of BAs in combating infections, we have initiated an in-depth investigation into the interactions between BAs and intestinal microbiota. Leveraging the existing literature, we offer a comprehensive analysis of the relationships between BAs and 16 key microbiota. This investigation encompasses bacteria (e.g., Clostridioides difficile (C. difficile), Staphylococcus aureus (S. aureus), Escherichia coli, Enterococcus, Pseudomonas aeruginosa, Mycobacterium tuberculosis (M. tuberculosis), Bacteroides, Clostridium scindens (C. scindens), Streptococcus thermophilus, Clostridium butyricum (C. butyricum), and lactic acid bacteria), fungi (e.g., Candida albicans (C. albicans) and Saccharomyces boulardii), and viruses (e.g., coronavirus SARS-CoV-2, influenza virus, and norovirus). Our research found that Bacteroides, C. scindens, Streptococcus thermophilus, Saccharomyces boulardii, C. butyricum, and lactic acid bacteria can regulate the metabolism and function of BSHs and 7α-dehydroxylase. BSHs and 7α-dehydroxylase play crucial roles in the conversion of primary bile acid (PBA) to secondary bile acid (SBA). It is important to note that PBAs generally promote infections, while SBAs often exhibit distinct anti-infection roles. In the antimicrobial action of BAs, SBAs demonstrate antagonistic properties against a wide range of microbiota, with the exception of norovirus. Given the intricate interplay between BAs and intestinal microbiota, and their regulatory effects on infections, we assert that BAs hold significant potential as a novel approach for preventing and treating microbial infections.

Single nucleus RNA sequencing (snRNA-seq), an alternative to single cell RNA sequencing (scRNA-seq), encounters technical challenges in obtaining high-quality nuclei and RNA, persistently hindering its applications. Here, we present a robust technique for isolating nuclei across various tissue types, remarkably enhancing snRNA-seq data quality. Employing this approach, we comprehensively characterize the depot-dependent cellular dynamics of various cell types underlying adipose tissue remodeling during obesity. By integrating bulk nuclear RNA-seq from adipocyte nuclei of different sizes, we identify distinct adipocyte subpopulations categorized by size and functionality. These subpopulations follow two divergent trajectories, adaptive and pathological, with their prevalence varying by depot. Specifically, we identify a key molecular feature of dysfunctional hypertrophic adipocytes, a global shutdown in gene expression, along with elevated stress and inflammatory responses. Furthermore, our differential gene expression analysis reveals distinct contributions of adipocyte subpopulations to the overall pathophysiology of adipose tissue. Our study establishes a robust snRNA-seq method, providing novel insights into the biological processes involved in adipose tissue remodeling during obesity, with broader applicability across diverse biological systems.

The human microbiota is an intricate micro-ecosystem comprising a diverse range of dynamic microbial populations mainly consisting of bacteria, whose interactions with hosts strongly affect several physiological and pathological processes. The gut microbiota is being increasingly recognized as a critical player in maintaining homeostasis, contributing to the main functions of the intestine and distal organs such as the brain. However, gut dysbiosis, characterized by composition and function alterations of microbiota with intestinal barrier dysfunction has been linked to the development and progression of several pathologies, including intestinal inflammatory diseases, systemic autoimmune diseases, such as rheumatic arthritis, and neurodegenerative diseases, such as Alzheimer's disease. Moreover, oral microbiota research has gained significant interest in recent years due to its potential impact on overall health. Emerging evidence on the role of microbiota-host interactions in health and disease has triggered a marked interest on the functional role of bacterial extracellular vesicles (BEVs) as mediators of inter-kingdom communication. Accumulating evidence reveals that BEVs mediate host interactions by transporting and delivering into host cells effector molecules that modulate host signaling pathways and cell processes, influencing health and disease. This review discusses the critical role of BEVs from the gut, lung, skin and oral cavity in the epithelium, immune system, and CNS interactions.

The host microbiome can be considered an ecological community of microbes present inside a complex and dynamic host environment. The host is under selective pressure to ensure that its microbiome remains beneficial. The host can impose a range of ecological filters including the immune response that can influence the assembly and composition of the microbial community. How the host immune response interacts with the within-microbiome community dynamics to affect the assembly of the microbiome has been largely unexplored. We present here a mathematical framework to elucidate the role of host immune response and its interaction with the balance of ecological interactions types within the microbiome community. We find that highly mutualistic microbial communities characteristic of high community density are most susceptible to changes in immune control and become invasion prone as host immune control strength is increased. Whereas highly competitive communities remain relatively stable in resisting invasion to changing host immune control. Our model reveals that the host immune control can interact in unexpected ways with a microbial community depending on the prevalent ecological interactions types for that community. We stress the need to incorporate the role of host-control mechanisms to better understand microbiome community assembly and stability.

The prevalence of small intestinal bacterial overgrowth (SIBO) is rising worldwide, particularly in nations with high rates of urbanization. Irritable bowel syndrome, inflammatory bowel illnesses, and nonspecific dysmotility are strongly linked to SIBO. Moreover, repeated antibiotic therapy promotes microorganisms' overgrowth through the development of antibiotic resistance. The primary cause of excessive fermentation in the small intestine is a malfunctioning gastrointestinal motor complex, which results in the gut's longer retention of food residues. There are anatomical and physiological factors affecting the functioning of the myoelectric motor complex. Except for them, diet conditions the activity of gastrointestinal transit. Indisputably, the Western type of nutrition is unfavorable. Some food components have greater importance in the functioning of the gastrointestinal motor complex than others. Tryptophan, an essential amino acid and precursor of the serotonin hormone, accelerates intestinal transit, and gastric emptying, similarly to fiber and polyphenols. Additionally, the effect of food on the microbiome is important, and diet should prevent bacterial overgrowth and exhibit antimicrobial effects against pathogens. Therefore, knowledge about proper nutrition is essential to prevent the development and recurrence of SIBO. Since the scientific world was unsure whether there was a long-term or potential solution for SIBO until quite recently, research on a number of the topics included in the article should be performed. The article aimed to summarize current knowledge about proper nutrition after SIBO eradication and the prevention of recurrent bacterial overgrowth. Moreover, a connection was found between diet, gut dysmotility, and SIBO.

Neurodegenerative disorders are a group of diseases characterized by progressive degeneration of the nervous system, leading to a gradual loss of previously acquired motor, sensory and/or cognitive functions. Leukodystrophies are amongst the most frequent childhood-onset neurodegenerative diseases and primarily affect the white matter of the brain, often resulting in neuro-motor disability. Notably, gastrointestinal (GI) symptoms and complications, such as gastroesophageal reflux disease (GERD) and dysphagia, significantly impact patients' quality of life, highlighting the need for comprehensive management strategies. Gut dysbiosis, characterized by microbial imbalance, has been implicated in various GI disorders and neurodegenerative diseases. This narrative review explores the intricate relationship between GI symptoms, Gut Microbiota (GM), and neurodegeneration. Emerging evidence underscores the profound influence of GM on neurological functions via the microbiota gut-brain axis. Animal models have demonstrated alterations in GM composition associated with neuroinflammation and neurodegeneration. Our single-centre experience reveals a high prevalence of GI symptoms in leukodystrophy population, emphasizing the importance of gastroenterological assessment and nutritional intervention in affected children. The bidirectional relationship between GI disorders and neurodegeneration suggests a potential role of gut dysbiosis in disease progression. Prospective studies investigating the GM in leukodystrophies are essential to understand the role of gut-brain axis dysfunction in disease progression and identify novel therapeutic targets. In conclusion, elucidating the interplay between GI disorders, GM, and neurodegeneration holds promise for precision treatments aimed at improving patient outcomes and quality of life.

Small intestinal bacterial overgrowth (SIBO) is a pathology of the small intestine and may predispose individuals to various nutritional deficiencies. Little is known about whether specific subtypes of SIBO, such as the hydrogen-dominant (H+), methane-dominant (M+), or hydrogen/methane-dominant (H+/M+), impact nutritional status and dietary intake in SIBO patients. The aim of this study was to investigate possible correlations between biochemical parameters, dietary nutrient intake, and distinct SIBO subtypes. This observational study included 67 patients who were newly diagnosed with SIBO. Biochemical parameters and diet were studied utilizing laboratory tests and food records, respectively. The H+/M+ group was associated with low serum vitamin D (p < 0.001), low serum ferritin (p = 0.001) and low fiber intake (p = 0.001). The M+ group was correlated with high serum folic acid (p = 0.002) and low intakes of fiber (p = 0.001) and lactose (p = 0.002). The H+ group was associated with low lactose intake (p = 0.027). These results suggest that the subtype of SIBO may have varying effects on dietary intake, leading to a range of biochemical deficiencies. Conversely, specific dietary patterns may predispose one to the development of a SIBO subtype. The assessment of nutritional status and diet, along with the diagnosis of SIBO subtypes, are believed to be key components of SIBO therapy.

Although diabetic gastroenteropathy (DGE) is associated with small intestinal bacterial overgrowth (SIBO), most studies have evaluated SIBO with a hydrogen breath test, which may be affected by altered transit in DGE. The risk factors for the consequences of SIBO in DGE are poorly understood. We aimed to evaluate the prevalence of, risk factors for, and gastrointestinal symptoms associated with SIBO in patients with DGE.

In 75 patients with DGE and dyspepsia, we tested for SIBO (≥105 colony forming units /mL of aerobic and/or anaerobic bacteria in a duodenal aspirate) and assessed gastric emptying (GE) of solids, symptoms during a GE study and during an enteral lipid challenge (300 kcal/2 h), and daily symptoms with a Gastroparesis Cardinal Symptom Index diary for 2 weeks. Symptoms and GE were compared in patients with versus without SIBO.

Of 75 patients, 34 (45%) had SIBO, which was not associated with the use of proton pump inhibitors, daily symptoms, GE, or symptoms during a GE study. During enteral lipid challenge, severe nausea (p = 0.006), fullness (p = 0.02) and bloating (p = 0.009) were each associated with SIBO. Twenty patients (59%) with versus 13 (32%) without SIBO had at least one severe symptom during the lipid challenge (p = 0.006).

Among patients with DGE 45% had SIBO, which was associated with symptoms during enteral lipid challenge but not with delayed GE, symptoms during a GE study, or daily symptoms. Perhaps bacterial products and even fatty acids are recognized by and activate mast cells that drive the increased lipid sensitivity in SIBO.

Postprandial, or meal-related, symptoms, such as abdominal pain, early satiation, fullness or bloating, are often reported by patients with disorders of gut-brain interaction, including functional dyspepsia (FD) or irritable bowel syndrome (IBS). We propose that postprandial symptoms arise via a distinct pathophysiological process. A physiological or psychological insult, for example, acute enteric infection, leads to loss of tolerance to a previously tolerated oral food antigen. This enables interaction of both the microbiota and the food antigen itself with the immune system, causing a localised immunological response, with activation of eosinophils and mast cells, and release of inflammatory mediators, including histamine and cytokines. These have more widespread systemic effects, including triggering nociceptive nerves and altering mood. Dietary interventions, including a diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols, elimination of potential food antigens or gluten, IgG food sensitivity diets or salicylate restriction may benefit some patients with IBS or FD. This could be because the restriction of these foods or dietary components modulates this pathophysiological process. Similarly, drugs including proton pump inhibitors, histamine-receptor antagonists, mast cell stabilisers or even tricyclic or tetracyclic antidepressants, which have anti-histaminergic actions, all of which are potential treatments for FD and IBS, act on one or more of these mechanisms. It seems unlikely that food antigens driving intestinal immune activation are the entire explanation for postprandial symptoms in FD and IBS. In others, fermentation of intestinal carbohydrates, with gas release altering reflex responses, adverse reactions to food chemicals, central mechanisms or nocebo effects may dominate. However, if the concept that postprandial symptoms arise from food antigens driving an immune response in the gastrointestinal tract in a subset of patients is correct, it is paradigm-shifting, because if the choice of treatment were based on one or more of these therapeutic targets, patient outcomes may be improved.

Chronic visceral pain is one of the most common reasons for patients with gastrointestinal disorders, such as inflammatory bowel disease or disorders of brain-gut interaction, to seek medical attention. It represents a substantial burden to patients and is associated with anxiety, depression, reductions in quality of life, and impaired social functioning, as well as increased direct and indirect health care costs to society. Unfortunately, the diagnosis and treatment of chronic visceral pain is difficult, in part because our understanding of the underlying pathophysiologic basis is incomplete. In this review, we highlight recent advances in peripheral pain signaling and specific physiologic and pathophysiologic preclinical mechanisms that result in the sensitization of peripheral pain pathways. We focus on preclinical mechanisms that have been translated into treatment approaches and summarize the current evidence base for directing treatment toward these mechanisms of chronic visceral pain derived from clinical trials. The effective management of chronic visceral pain remains of critical importance for the quality of life of suffers. A deeper understanding of peripheral pain mechanisms is necessary and may provide the basis for novel therapeutic interventions.

There is compelling evidence that microbe-host interactions in the intestinal tract underlie many human disorders, including disorders of gut-brain interactions (previously termed functional bowel disorders), such as irritable bowel syndrome (IBS). Small intestinal bacterial overgrowth (SIBO) has been recognized for over a century in patients with predisposing conditions causing intestinal stasis, such as surgical alteration of the small bowel or chronic diseases, including scleroderma and is associated with diarrhea and signs of malabsorption. Over 20 years ago, it was hypothesized that increased numbers of small intestine bacteria might also account for symptoms in the absence of malabsorption in IBS and related disorders. This SIBO-IBS hypothesis stimulated significant research and helped focus the profession's attention on the importance of microbe-host interactions as a potential pathophysiological mechanism in IBS.

However, after two decades, this hypothesis remains unproven. Moreover, it has led to serious unintended consequences, namely the widespread use of unreliable and unvalidated breath tests as a diagnostic test for SIBO and a resultant injudicious use of antibiotics. In this review, we examine why the SIBO hypothesis remains unproven and, given the unintended consequences, discuss why it is time to reject this hypothesis and its reliance on breath testing. We also examine recent IBS studies of bacterial communities in the GI tract, their composition and functions, and their interactions with the host. While these studies provide important insights to guide future research, they highlight the need for further mechanistic studies of microbe-host interactions in IBS patients before we can understand their possible role in diagnosis and treatment of patient with IBS and related disorders.

Glucose breath test (GBT) is used for the diagnosis of small intestine bacterial overgrowth. A restrictive diet without fibers and/or fermentable food is recommended on the day before the test. The aim of our retrospective study was to evaluate the impact of two different restrictive diets on the results of GBT.

A change of the pretest restrictive diet was applied in our lab on September 1, 2020. The recommended diet was a fiber-free diet before this date, and a fiber-free diet plus restriction of all fermentable food afterward. We thus compared the results of GBT performed before (group A) and after (group B) this pretest diet modification. Demographics, reasons to perform GBT, digestive symptoms, and hydrogen and methane baseline values and variations after glucose ingestion were compared between the two groups.

269 patients underwent GBT in group A, and 316 patients in group B. The two groups were comparable in terms of demographics. Methane and hydrogen baseline values were significantly higher in group A (respectively 14 [18] vs. 8 [14] ppm, p < 0.01 and 11 [14] vs. 6 [8] ppm, p < 0.01). The percentage of positive tests was higher in group A for methane (43% vs. 28%, p < 0.05), and for hydrogen (18% vs. 12%, p = 0.03).

This retrospective study suggests the importance of the restrictive diet prior to GBT. A strict limitation of fibers and fermentable food decreased hydrogen and methane baseline values, and the prevalence of positive GBT. Thus a strict restrictive diet should be recommended on the day before the test, in order to limit the impact of food on hydrogen and methane breath levels, and possibly improve the diagnosis quality of GBT.

Small intestinal bacterial overgrowth (SIBO) is the presence of an abnormally excessive amount of bacterial colonization in the small bowel. Hydrogen and methane breath test has been widely applied as a non-invasive method for SIBO. However, the positive breath test representative of bacterial overgrowth could also be detected in asymptomatic individuals.

To explore the relationship between clinical symptoms and gut dysbiosis, and find potential fecal biomarkers for SIBO, we compared the microbial profiles between SIBO subjects with positive breath test but without abdominal symptoms (PBT) and healthy controls (HC) using 16S rRNA amplicon sequencing.

Fecal samples were collected from 63 SIBO who complained of diarrhea, distension, constipation, or abdominal pain, 36 PBT, and 55 HC. For alpha diversity, the Shannon index of community diversity on the genus level showed a tendency for a slight increase in SIBO, while the Shannon index on the predicted function was significantly decreased in SIBO. On the genus level, significantly decreased Bacteroides, increased Coprococcus_2, and unique Butyrivibrio were observed in SIBO. There was a significant positive correlation between saccharolytic Coprococcus_2 and the severity of abdominal symptoms. Differently, the unique Veillonella in the PBT group was related to amino acid fermentation. Interestingly, the co-occurrence network density of PBT was larger than SIBO, which indicates a complicated interaction of genera. Coprococcus_2 showed one of the largest betweenness centrality in both SIBO and PBT microbiota networks. Pathway analysis based on the Kyoto Encyclopedia of Genes and Genome (KEGG) database reflected that one carbon pool by folate and multiple amino acid metabolism were significantly down in SIBO.

This study provides valuable insights into the fecal microbiota composition and predicted metabolic functional changes in patients with SIBO. Butyrivibrio and Coprococcus_2, both renowned for their role in carbohydrate fermenters and gas production, contributed significantly to the symptoms of the patients. Coprococcus's abundance hints at its use as a SIBO marker. Asymptomatic PBT individuals show a different microbiome, rich in Veillonella. PBT's complex microbial interactions might stabilize the intestinal ecosystem, but further study is needed due to the core microbiota similarities with SIBO. Predicted folate and amino acid metabolism reductions in SIBO merit additional validation.

Irritable bowel syndrome (IBS), one of the most prevalent functional gastrointestinal disorders, is characterized by recurrent abdominal pain and abnormal defecation habits, resulting in a severe healthcare burden worldwide. The pathophysiological mechanisms of IBS are multi-factorially involved, including food antigens, visceral hypersensitivity reactions, and the brain-gut axis. Numerous studies have found that gut microbiota and intestinal mucosal immunity play an important role in the development of IBS in crosstalk with multiple mechanisms. Therefore, based on existing evidence, this paper elaborates that the damage and activation of intestinal mucosal immunity and the disturbance of gut microbiota are closely related to the progression of IBS. Combined with the application prospect, it also provides references for further in-depth exploration and clinical practice.

Our understanding of region-specific microbial function within the gut is limited due to reliance on stool. Using a recently developed capsule device, we exploit regional sampling from the human intestines to develop models for interrogating small intestine (SI) microbiota composition and function. In vitro culturing of human intestinal contents produced stable, representative communities that robustly colonize the SI of germ-free mice. During mouse colonization, the combination of SI and stool microbes altered gut microbiota composition, functional capacity, and response to diet, resulting in increased diversity and reproducibility of SI colonization relative to stool microbes alone. Using a diverse strain library representative of the human SI microbiota, we constructed defined communities with taxa that largely exhibited the expected regional preferences. Response to a fiber-deficient diet was region-specific and reflected strain-specific fiber-processing and host mucus-degrading capabilities, suggesting that dietary fiber is critical for maintaining SI microbiota homeostasis. These tools should advance mechanistic modeling of the human SI microbiota and its role in disease and dietary responses.