Correlation between the neuroendocrine axis, microbial species, inflammatory response, and gastrointestinal symptoms in irritable bowel syndrome.

BACKGROUND: This study examines the complex relationships among the neuroendocrine axis, gut microbiome, inflammatory responses, and gastrointestinal symptoms in patients with irritable bowel syndrome (IBS). The findings provide new insights into the pathophysiology of IBS and suggest potential therapeutic targets for improving patient outcomes. AIM: To investigate the interactions between the neuroendocrine axis, gut microbiome, inflammation, and gastrointestinal symptoms in patients with IBS. METHODS: Patients diagnosed with IBS between January 2022 and January 2023 were selected for the study. Healthy individuals undergoing routine check-ups during the same period served as the control group. Data were collected on neuroendocrine hormone levels, gut microbiome profiles, inflammatory biomarkers, and gastrointestinal symptomatology to analyze their interrelations and their potential roles in IBS pathogenesis. RESULTS: IBS patients exhibited significant dysregulation of the neuroendocrine axis, with altered levels of cortisol, serotonin, and neuropeptides compared to healthy controls. The gut microbiome of IBS patients showed reduced diversity and specific alterations in bacterial genera, including Bifidobacterium, Lactobacillus, and Faecalibacterium, which were associated with neuroendocrine disturbances. Additionally, elevated levels of inflammatory markers, such as C-reactive protein, interleukin-6, and tumor necrosis factor-α, were observed and correlated with the severity of gastrointestinal symptoms like abdominal pain, bloating, and altered bowel habits. CONCLUSION: The findings suggest that targeting the neuroendocrine axis, gut microbiome, and inflammatory pathways may offer novel therapeutic strategies to alleviate symptoms and improve the quality of life in IBS patients.

Suppression of certain intestinal microbiota metabolites may lead to gestational diabetes in mice fed a high-fat diet.

Background: We aim to establish a gestational diabetes mellitus (GDM) mouse model with mice fed with a high-fat diet (HFD) in comparison with pregnant mice with normal blood glucose levels to investigate the role of intestinal microbiota in the development of HFD-induced GDM. Methods: We divided healthy 6-week-old female C57BL mice into an HFD-induced GDM group and a normal diet group. Their bacterial flora and metabolites in intestinal fecal exosomes were co-analyzed using 16 s multi-region sequencing and compared. Findings: Alpha (α) diversity was lower within the model group compared to the control group. Beta (ß) diversity was significantly different between the two groups. The relative abundances of Lactobacillus, Actinomyces, Rothia, and Bacteroidetes were significantly different between the two groups. Fermentation and nitrate consumption were significantly higher in the GDM group. Multiple bacteria were associated with glycerophosphocholine, S-methyl-5'-thioadenosine, quinolinate, galactinol, deoxyadenosine, DL-arginine, and 2-oxoadenic acid. Interpretation: Imbalances in the production of Lactobacillus, Bacteroidetes, Actinomyces, and Rothia and their related metabolites may lead to metabolic disturbances in GDM. These indicators may be used to assess changes affecting the intestinal microbiota during pregnancy and thus help modulate diet and alter blood glucose.

[Induction and regulation of intestinal graft-versus-host disease by the intestinal microbiota].

The intestinal microbiota is an important prognostic factor for allogeneic hematopoietic stem cell transplantation (allo-HCT), and decreased diversity of the intestinal microbiota is linked to shorter overall survival, high transplant-related mortality, and acute graft-versus-host disease (GVHD). Major factors that alter the intestinal microbiota during allo-HCT are broad-spectrum antibiotics and intestinal GVHD. Broad-spectrum antibiotics dysregulate the immune system and impair intestinal epithelial regeneration by reducing beneficial commensal bacteria and activating mucus-degrading bacteria, which disrupts the colonic barrier function. Intestinal GVHD leads to decreased secretion of antimicrobial peptides into the intestinal lumen, as well as mitochondrial dysfunction in the intestinal epithelium, altering the intestinal microbiota. Various therapeutic approaches targeting the intestinal microbiota have been investigated in clinical trials. Protecting the intestinal microbiota may further enhance the safety and efficacy of allo-HCT by regulating intestinal immune responses, promoting intestinal epithelial regeneration, and facilitating the production of beneficial metabolites derived from commensal bacteria.

Glycaemic sugar metabolism and the gut microbiota: past, present and future.

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.

Correlation Analysis of Characteristics of Intestinal Microbiota and Cytokine Levels in Patients with Obstructive Sleep Apnea-Hypopnea Syndrome.

Objective: The aim of this study was to analyze the relationship between the characteristics of the intestinal microbiota and cytokine levels in individuals with different degrees of obstructive sleep apnea-hypopnea syndrome (OSAHS) as well as to investigate intestinal microbiota imbalances in patients with OSAHS and the associated mechanisms. Methods: Based on their sleep apnea hypopnea index (AHI), a total of 37 adults were assigned to a control group, a mild OSAHS group, or a moderate-to-severe OSAHS group. Fecal samples were collected to characterize the intestinal microbiota using metagenomic next-generation sequencing (mNGS), while blood samples were collected to detect levels of interleukin-17a (IL-17a), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) in each group. Results: 1. There was no significant difference in the Shannon index among the three groups (P > 0.05). The three groups showed significant difference in the relative abundance of Faecalibacterium prausnitzii and Bifidobacterium adolescentis (with F values of 3.955 and 7.24, respectively, P < 0.05), while showed no significant difference in the relative abundance of B. pseudocatenulatum, Bifidobacterium longum, Klebsiella pneumoniae, and Haemophilus parainfluenzae (P > 0.05). 2. The three groups showed significant difference in the expression of serum IL-17A and TNF-α levels (with F values of 18.119 and 10.691, respectively, P < 0.05), while showed no significant difference in the expression of IL-10, IL-6, and CRP levels (P > 0.05). 3. Multiple linear regression analysis revealed that the relative abundance of F. prausnitzii was correlated with changes in BMI and AHI (with ß values of 2.585 and -0.157, respectively, P < 0.05), while the relative abundance of B. adolescentis was correlated with changes in IL-17a (with ß value of -0.161, P < 0.05). Conclusion: The study revealed a significant correlation between intestinal microbiota abundance and cytokine levels, suggesting that gut microbiota disruption in OSAHS patients may be linked to systemic chronic inflammation.

Xiaobugan decoction prevents CCl4-induced acute liver injury by modulating gut microbiota and hepatic metabolism.

BACKGROUND: The liver plays a crucial role in detoxification and metabolism. When its capacity to metabolize foreign substances is exceeded, it can lead to acute liver injury (ALI). Therefore, preventing liver disease and maintaining daily liver health are of utmost importance. Xiaobugan Decoction (XBGD), a traditional Chinese medicine (TCM) formula, is recorded in 'Fuxingjue', is used in folk practice to promote liver health and regulate respiration. However, the hepatoprotective mechanisms of XBGD remained unclear. PURPOSE: We investigated the prophylactic and hepatoprotective effects of XBGD and explored its related molecular mechanisms using a mouse model of carbon tetrachloride (CCl4)-induced ALI. STUDY DESIGN AND METHODS: XBGD composition was determined using analytical methods, and the main compounds were identified using ultra-high-performance liquid chromatography coupled with Q-Exactive focus mass spectrum (UHPLC-QE-MS) and high-performance liquid chromatography (HPLC). A CCl4-induced L02 cell injury model was employed to explore the protective effects of XBGD on liver cells, and a CCl4-induced ALI mouse model was used to investigate the hepatoprotective effects of XBGD. RESULTS: Cellular experiments demonstrated that XBGD had a protective function against L02 cell damage by increasing cell viability, restoring alanine aminotransferase (ALT), aspartate aminotransferase (AST), and superoxide dismutase (SOD) levels, reducing malondialdehyde (MDA) content, and improving mitochondrial membrane potential (ΔΨm). In the mouse ALI model, XBGD prevented ALI by reducing ALT, AST, and alkaline phosphatase (ALP) levels and inhibiting oxidative stress. Quantitative real-time polymerase chain reaction (qPCR), immumohistochemical staining and western blotting results revealed that XBGD exerted hepatoprotective effects by reducing inflammatory responses and inhibiting cell apoptosis. Furthermore, 1H-NMR metabolomics indicated that XBGD regulates hepatic and intestinal metabolism, whereas 16S rDNA sequencing demonstrated the regulatory effects of XBGD on the gut microbiota. Correlation analysis highlighted the close relationship among gut microbiota, metabolites, and ALI indicators. CONCLUSIONS: XBGD is a promising TCM for the prevention of CCl4-induced ALI via regulation of microbiota and metabolism. This study provides a new perspective on the development of hepatoprotective measures and the prevention of liver disease in daily life.

Effects of cottonseed meal protein hydrolysate on intestinal microbiota of yellow-feather broilers.

We evaluated the effects of cottonseed meal protein hydrolysate (CPH) on the intestinal microbiota of yellow-feather broilers. We randomly divided 240 chicks into four groups with six replicates: basal diet with 0% (CON), 1% (LCPH), 3% (MCPH), or 5% (HCPH) CPH. The test lasted 63 days and included days 1-21, 22-42, and 43-63 phases. The ACE, Chao1, and Shannon indices in the MCPH and HCPH groups of 42-day-old broilers were higher than those in the CON group (p < 0.05), indicating that the cecum microbial diversity and richness were higher in these groups. Firmicutes and Bacteroidetes were the dominant phyla; however, the main genera varied during the different periods. The abundance of Lactobacillus in CPH treatment groups of 21-day-old broilers was high (p < 0.05); in the 42-day-old broilers, the abundances of Barnesiella, Clostridia_vadinBB60_group, and Parasutterella in the LCPH group, Desulfovibrio, Lactobacillus, Clostridia_vadinBB60_group, and Butyricicoccus in the MCPH group, and Megamonas and Streptococcus in the HCPH group increased; in the 63-day-old broilers, the abundance of Clostridia_UCG-014 and Synergistes in the LCPH and HCPH group, respectively, increased (p < 0.05), and that of Alistipes in the LCPH and MCPH groups decreased (p < 0.05). And changes in the abundance of probiotics were beneficial to improve the intestinal morphology and growth performance. In addition, the LCPH treatment increased the complexity of the microbial network, while the MCPH treatment had the same effect in 42-day-old broilers. Thus, CPH increased the relative abundance of beneficial intestinal microbiota and enhanced the richness and diversity of the bacterial microbiota in broilers aged <42 days; this effect was weakened after 42 days.

Dietary Clostridium butyricum metabolites mitigated the disturbances in growth, immune response and gut health status of Ctenopharyngodon idella subjected to high cottonseed and rapeseed meal diet.

Cottonseed meal and rapeseed meal exhibit a potential for fishmeal substitute in grass carp feed, while their excessive use contribute to growth decline and weakening immunity of aquatic animals. Clostridium butyricum metabolites (CBM) was recognized as a functional additive due to its antioxidant properties and maintenance of intestinal microbiota balance. CBM was added to a high of cottonseed and rapeseed meal diet to determine its effects on growth, immunity, and intestinal microbiota alterations of grass carp (Ctenopharyngodon idella) over 56 days. Eight hundred grass carp (mean weight, around 50 g) were randomized to five treatments and fed with the basic diet (CON), CBM0 diet (28 % cottonseed and 27 % rapeseed meal), and CBM diets (CBM0.5, CBM1, and CBM2, namely CBM0 diet supplemented with 500, 1000, and 2000 mg kg-1 CBM). The results indicated that compared to CBM0, The ingestion of 1000 mg kg-1 CBM diet by grass carp significantly promoted growth as measured by intestinal lipase activity, villus height, and muscle thickness. Moreover, accompanied by a decrease in intestine MDA content, and enhance antioxidant capacity by activating Keap1/Nrf2 signaling pathway to increase enzyme activities (SOD, CAT and T-AOC) and corresponding gene expression (mnsod, cat, gsto and gpx1) in the intestine of grass crap fed CBM1 diet. The dietary CBM1 diet increased serum levels of C3 and IgM, increased ACP activity and expression of the corresponding anti-inflammatory factors (tgf-ß1 and il-15), and suppressed the expression of pro-inflammatory factors (tnf-α and il-12ß), resulting in enhanced immunity. The dietary CBM1 diet up-regulates gene expression of tight junction proteins (zo-1, occludin, occludin7a and occludin-c), coupled with the decreases in DAO and D-lactate contents, implying that the decreased mucosal permeability could be observed in the gut. The dietary CBM1 diet largely altered the intestinal microbial community, especially reducing the relative abundance of intestinal pathogenic bacteria (Streptococcus and Actinomyces). And it significantly increased the content of short-chain fatty acids (acetic acid, butyric acid, isobutyric acid, propionic acid and isovaleric acid). Taken above, dietary CBM supplementation improved growth in grass carp and attenuated the intestinal oxidative stress, inflammation and microflora dysbacteriosis caused by high proportions of cottonseed and rapeseed meal diets.

Cogrowth advantage: Intestinal microbiota analysis of Bufo gargarizans and Rana chensinensis.

Intestinal microbiota has profound effects on host health and adaptation to environmental changes. Bufo gargarizans and Rana chensinensis coexist in the same habitat and have been paid much attention to economically because of their medicinal value. To date, no comparison of differences between single and mixed populations has been made. In our study, differences in the structure and function of the intestinal microbial of B. gargarizans and R. chensinensis in environments of single-species and mixed-species growth were investigated by high-throughput sequencing. Our results suggest that the cogrowth of B. gargarizans and R. chensinensis could lead to the decrease of the abundance of pathogenic bacteria (Bosea) and the introduction or increase of beneficial bacteria (Kaistia, Cetobacterium and Erysipelatoclostridium). The Tax4Fun-based functional predictions revealed that the level of pathways involved in the metabolism of R. chensinensis in mixed-species aquaria is greatly up-regulated. This study provides useful information for ecologists, ecosystem policy makers and wildlife conservationists to promote more effective conservation measures.

Impact of bariatric surgery on gut microbiota composition in obese patients compared to healthy controls.

Bariatric surgery is vital for sustainable weight loss and metabolic improvement in obese individuals, but its effects on gut microbiota and their role in these benefits require further investigation. Investigate the temporal changes in gut microbiota in obese patients undergoing bariatric surgery (gastric sleeve gastrectomy or Roux-en-Y Gastric Bypass (RYGB)) compared to healthy controls, aiming to understand their role in weight loss and metabolic health improvement. A case-control study included 30 obese patients aged 65-95 undergoing bariatric surgery, and 18 matched healthy controls. Selection criteria were based on age, race, BMI, history of antibiotics, probiotics, and prebiotics usage. Stool samples were collected at baseline, three months, and six months post-surgery for DNA extraction and quantitative real-time PCR analysis to assess gut microbiota changes. Physical activity and dietary intake were evaluated using standardized questionnaires. Statistical analyses were performed using R. Post-surgery, patients showed significant reductions in weight and BMI, with changes in dietary habits and physical activity. Quantitative real-time PCR analysis revealed substantial alterations in bacterial groups such as Bacteroides and Fusobacterium. However, some groups showed no significant changes, indicating a complex interaction between gut microbiota and bariatric surgery. Notable correlations were found between body weight, BMI, and specific bacterial groups like the C. cluster IV and Lactobacillus, particularly in RYGB patients. Bariatric surgery significantly alters gut microbiota, aiding weight loss and metabolic regulation in obese patients. Understanding these changes is crucial for developing effective obesity management strategies, requiring further research to optimize outcomes.

Metagenomics combined with untargeted metabolomics to study the mechanism of miRNA-150-5p on SiO2 -induced acute lung injury.

Acute lung injury is a significant global health issue, and its treatment is becoming a hot topic of the researchers. To investigate the feasibility of miRNA-150-5p tail vein injection in the treatment of SiO2-induced acute lung injury through the regulation of gut microbiota and serum metabolites based on multiomics technology. Twenty-four mice were randomly divided into the control, SiO2 and miRNA-150-5p intervention groups. The SiO2 and miRNA-150-5p intervention groups received a single intranasal dose of 100 µL 4 % SiO2 suspension. Meanwhile, the miRNA-150-5p intervention group was administered with two tail vein injections of miRNA-150-5p (15 nmol each per mouse) on the day of successful modelling and on the third day post modelling. Metagenomics and metabolomics techniques were used to measure gut microbiota and serum metabolites, respectively. Tail vein injection of miRNA-150-5p improved SiO2-induced acute lung injury and reduced the secretion of inflammatory factors interleukin (IL)-6, tumour necrosis factor-α and IL-1ß. These conditions altered the structure of gut microbiota, which resulted in the notable modulation of eight species at the species level. In addition, tail vein injection of miRNA-150-5p considerably reduced the levels of substances, such as phosphatidylethanolamine, phosphatidylcholine and phosphatidylinositol, in the glycerophospholipid metabolism and glycosylphosphatidylinositol-anchor biosynthesis pathways. Tail vein injection of miRNA-150-5p can alleviate acute lung injury. Combined metagenomics and untargeted metabolomics revealed the miRNA-150-5p-mitigated SiO2-induced acute lung injury that occurred through the regulation of gut microbiota and serum metabolites.

Intestinal microbiota composition in broilers fed protein-free or casein-based diets.

Growing broiler chickens of the Cobb500 strain were used to determine the effects on intestinal microbiota composition of a protein-free (PF) diet as compared to a diet based in casein (CAS) as the only protein source. CAS was formulated to contain the same amount of protein (190 g kg-1) as a commercial Maize-soy diet which was used as a practical reference. The ileal AA flow (g kg-1 dry matter intake) was significantly higher (P < 0.001) than PF in birds fed protein containing diets (CAS or Maize-soy). Taken as a whole (discriminant and ANOSIM analysis), the intestinal (ileal and caecal contents and ileal tissue) microbiota composition of PF and CAS were significantly (P < 0.001) different from Maize-soy and not different from each other in some cases. RT-qPCR and sequencing analysis of the ileal and caecal microbiota revealed significant (P < 0.05) differences in a number of bacterial groups between broilers fed PF, CAS or Maize-soy diets. The main result was that the lack of protein in the intestinal medium of PF birds resulted in a drop of Lactobacillus spp. counts (on average, 43 in PF vs 1,734 in the Maize-soy diet) and increased Enterobacteriaceae (on average, 419 in PF vs 172 in the Maize-soy diet) and other potentially pathogenic bacterial groups (in both intestinal contents and tissue). Thus, the lack of protein in the intestinal medium of PF birds resulted in a microbiota composition compatible with a pro-inflammatory state, and this effect was somewhat less marked in birds fed CAS. The results reported here suggest that the adverse effects on microbiota composition in broilers fed CAS were less marked than in those fed PF, which would be in line with a preferential use of a highly digestible protein containing diet to determine endogenous AA excretion instead of a PF diet.

Impact of Gut Microbiota and SCFAs in the Pathogenesis of PCOS and the Effect of Metformin Therapy.

Polycystic ovary syndrome (PCOS) is a complex disorder that impacts both the endocrine and metabolic systems, often resulting in infertility, obesity, insulin resistance, and cardiovascular complications. The aim of this study is to investigate the role of intestinal flora and its metabolites, particularly short-chain fatty acids (SCFAs), in the development of PCOS, and to assess the effects of metformin therapy on these components. SCFA levels in fecal and blood samples from women with PCOS (n=69) and healthy controls (n=18) were analyzed using Gas Chromatography-Mass Spectrometry (GC/MS) for precise measurement. Fecal microbiota were quantitatively detected by real-time polymerase chain reaction (PCR). To assess the efficacy of six months of metformin treatment, changes in the microbiota and SCFAs in the PCOS group (n=69) were also evaluated. The results revealed that women with PCOS exhibited a significant reduction in beneficial bacteria (namely, the C. leptum group and Prevotella spp.) alongside a notable overgrowth of opportunistic microorganisms (C. perfringens, C. difficile, Staphylococcus spp., and Streptococcus spp.). An overproduction of acetic acid (AA, FC=0.47, p<0.05) and valeric acid (VA, FC=0.54, p<0.05) suggests a link between elevated SCFAs and the development of obesity and PCOS. Interestingly, AA in the bloodstream might offer a protective effect against PCOS by ameliorating key symptoms such as high body mass index (r=-0.33, p=0.02), insulin resistance (r=-0.39, p=0.02), and chronic inflammation. Although serum SCFA levels showed non-significant changes following metformin treatment (p>0.05), the normalization of AA in the gut underscores that metformin exerts a more pronounced effect locally within the gastrointestinal tract. Furthermore, the study identified the most effective model for predicting the success of metformin therapy, based on serum concentrations of butyric acid (BA) and VA, achieving a 91% accuracy rate, 100% sensitivity, and 80% specificity. These promising findings highlight the potential for developing targeted interventions and personalized treatments, ultimately improving clinical outcomes for women with PCOS.

The characteristics of intestinal microbiota in patients with type 2 diabetes and the correlation with the percentage of T-helper cells.

Background: Type 2 diabetes (T2D) is related to intestinal microflora changes and immune inflammation. We aimed to investigate the pattern of intestinal flora-systematic T helper (Th) cell linkage in T2D patients. Methods: Participants with T2D diagnosed by physicians and healthy controls were enrolled in the study. The Th1, Th2, and Th17 cells from the peripheral blood were assessed by flow cytometry. The feces were collected. The V3-V4 variable region of 16S rRNA was sequenced and analyzed using bioinformatics. Principal coordinate analysis (PCoA) and non-metric multidimensional scaling (NMDS) analysis were performed to assess the beta diversity. The linear discriminant analysis (LDA) effect size (LEfSe) method was applied to identify amicrobial taxon specific to T2D. The Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was conducted to identify the metabolic pathways. A network analysis was conducted by constructing a co-occurrence network. Results: The percentages of the Th1 and Th17 cells in the peripheral blood were higher in patients with T2D than in controls. Among the top 30 genera of the intestinal microbiota, the levels of Lachnospiraceae_NK4A136_group, Ruminococcaceae_UCG002, and Eubacterium_hallii_group were lower in the patients with T2D than in controls. In the LEfSe analysis, it was observed that the Lachnospiraceae and Ruminococcaceae families were significantly different between patients with T2D and controls. Moreover, the Th1/Th2 ratio was positively correlated with the abundance of the Lachnoclostridium and Ruminococcus_torques_group genera. In the network analysis, the Th1/Th2 ratio, Ruminococcaceae_UCG-002, and Lachnospiraceae_NK4A136_group were the important nodes. Conclusion: This study provided a preliminary picture of the crosstalk between the intestinal microbiome and systematic Th cells in patients with T2D. The findings of the study suggested that the network relationship among the intestinal microbiota, metabolites, and CD4+T lymphocyte immunity was unbalanced in the patients with T2D, which might have promoted the development of T2D. This presents a therapeutic opportunity to modulate gut immune reaction and then chronic inflammation by manipulating microbiome-specific Th-cell response.

Research progress of traditional Chinese medicine on the treatment of diarrhea by regulating intestinal microbiota and its metabolites based on renal-intestinal axis.

Intestinal microbiota and its metabolites are involved in many physiological processes of the human body and play a vital role in maintaining human health. The occurrence of kidney disease can cause intestinal microbiota imbalance, resulting in diarrhea. The change of intestinal microbiota and its metabolites content can aggravate renal function injury, which has a bidirectional regulating effect. The theory of renal-intestinal axis further clarified that the impaired renal function is related to the imbalance of intestinal microorganisms, and the impaired intestinal barrier is related to the accumulation of toxin products. Because of its unique therapeutic advantages, Traditional Chinese Medicine can treat diarrhea by enhancing the growth of beneficial bacteria, inhibiting pathogenic bacteria and immune regulation, and slow down the continuous deterioration of kidney disease. This paper focuses on the relationship between intestinal microbiota and its metabolites and diarrhea, the influence of Traditional Chinese Medicine on intestinal microbiota in the treatment of diarrhea, and the role of intestinal microbiota and its metabolites in the renal-intestinal axis. It provides a theoretical basis for Traditional Chinese Medicine to regulate intestinal microbiota and its metabolites based on the renal-intestinal axis theory to treat nephrology-induced diarrhea, and also provides a new idea and method for Traitional Chinese Medicine to treat nephrology-induced diarrhea.

Bie Jia Jian pill ameliorates BDL-induced cholestatic hepatic fibrosis in rats by regulating intestinal microbial composition and TMAO-mediated PI3K/AKT signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: As a compound of traditional Chinese medicine (TCM), Bie Jia Jian pill (BJJP) is extensively used to treat the clinical chronic liver disease. Nevertheless, the specific mechanism through which BJJP affects hepatic fibrosis (HF) remains unknown. AIM OF THE STUDY: To explore the role and potential mechanism of BJJP involved in treating HF. MATERIALS AND METHODS: HF model of Sprague-Dawley (SD) rats was induced by a bile duct ligation (BDL). The function of BJJP involved in the intestinal microbiota (IM) and its metabolites in BDL-induced HF rats were explored through the 16S rRNA sequencing and untargeted metabolomics technologies. Network pharmacology was used to forecast mechanism underlying BJJP's anti-HF effects, which were validated in BDL-induced rats and trimethylamine N-oxide (TMAO)-induced LX-2 and HSC-T6 cells. RESULTS: BJJP effectively ameliorated pathological liver damage, inflammation, and fibrosis of the BDL-induced HF rats. BJJP regulated IM diversity and composition and interfered with trimethylamine (TMA)-flavin monooxygenase 3 (FMO3)-TMAO process. In vitro, BJJP significantly inhibited the TMAO-induced activation of hepatic stellate cells (HSCs) (rat HSC cell line, HSC-T6; human HSC cell line, LX-2). Network pharmacology results demonstrated that PI3K/AKT signal pathway is crucially involved in BJJP treatment of HF. Further research revealed that BJJP inhibited the PI3K/AKT signal pathway in BDL-induced HF rats. Moreover, TMAO activated the PI3K/AKT pathway, whereas BJJP suppressed TMAO-induced activation. Subsequent intervention with 740Y-P (the PI3K agonist) successfully neutralized the repression effect on PI3K/AKT signal pathway by BJJP. CONCLUSION: These results clearly show that BJJP attenuates HF by regulating the IM, as well as inhibiting PI3K/AKT pathway mediated by TMAO.

Intestinal microbiota dysbiosis contributes to the liver damage in subchronic arsenic-exposed mice.

There is an extensive amount of evidence that links changes in the intestinal microbiota structure to the progression and pathophysiology of many liver diseases. However, comprehensive analysis of gut flora dysbiosis in arsenic-induced hepatotoxicity is lacking. Herein, C57BL/6 mice are exposed to arsenic (1, 2, or 4 mg/kg) for 12 weeks, after which fecal microbiota transplantation (FMT) study is conducted to confirm the roles of the intestinal microbiome in pathology. Treatment with arsenic results in pathological and histological changes in the liver, such as inflammatory cell infiltration and decreased levels of TP and CHE but increased levels of ALP, GGT, TBA, AST, and ALT. Arsenic causes an increase in the relative abundance of Escherichia-Shigella, Klebsiella and Blautia, but a decrease in the relative abundance of Muribaculum and Lactobacillus. In arsenic-exposed mice, protein expressions of Occludin, ZO-1, and MUC2 are significantly decreased, but the level of FITC in serum is increased, and FITC fluorescence is extensively dispersed in the intestinal tract. Importantly, FMT experiments show that mice gavaged with stool from arsenic-treated mice exhibit severe inflammatory cell infiltration in liver tissues. Arsenic-manipulated gut microbiota transplantation markedly facilitates gut flora dysbiosis in the recipient mice, including an up-regulation in Escherichia-Shigella and Bacteroides, and a down-regulation in Lactobacillus and Desulfovibrio. In parallel with the intestinal microbiota wreck, protein expressions of Occludin, ZO-1, and MUC2 are decreased. Our findings suggest that subchronic exposure to arsenic can affect the homeostasis of the intestinal microbiota, induce intestinal barrier dysfunction, increase intestinal permeability, and cause damage to liver tissues in mice.

[Effect of low doses of active chlorine on commensal populations of intestinal bacteria in rats by oral ingestion].

Chlorine-containing substances are widely used as disinfectants for treating equipment surfaces and technological aids for antimicrobial treatment of a number of foodstuff in the food industry. The toxic and bactericidal effects of the active (free) chlorine they contain are well understood for the concentrations used in practice, whereas little is known about the effect of its residual (subinhibitory) amounts on the organism and on the microbiota, including the ability to induce antimicrobial resistance. The aim of the study was to investigate the effect of different doses of active chlorine at oral administration on the commensal bacteria of intestinal microbiota, body weight gain and micromorphological features of the liver in rats. Material and methods. The study was carried out on male Wistar rats, with an initial body weight of 90-100 g, which for 4 weeks received doses of active chlorine together with drinking water ad libitum, with the given concentration: subinhibitory (10 mg/L), threshold (50 mg/L) and aggravated (100 mg/L). Chloramine was used as a chlorinecontaining agent stable in aqueous solution. Body weight gain was monitored daily. After decapitation, the caecum was taken for microbiota examination as well as the liver. The phenotypic antimicrobial resistance characteristics of Enterobacteriaceae and Enterococci were studied by the disk diffusion method. Additionally, a micromorphologic study of liver slices was performed. Results. Insignificant negative deviations in the body weight gain of rats in the experimental groups receiving subinhibitory doses of active chlorine, combined with a reduced level of Enterococci and Enterobacteriaceae representatives, were revealed. No significant effect of chlorine on the levels of resistant Escherichia coli populations was found, but a tendency to exhibit antimicrobial resistance of Enterococci isolated from rats receiving low doses of active chlorine (10 and 50 mg/l) was detected. No signs of toxic effect on the liver tissue most sensitive to chlorine were detected, but some accumulations of inflammatory cells in the liver slice were revealed. Conclusion. Low doses of chlorine-containing substances at their oral consumption are not indifferent for rats' organism, causing negative phenomena in intestinal bacteria and in liver tissues at the level of tendency. It is expedient to continue studies in this direction.

Increased dietary protein rather than fiber supports key metabolic and intestinal tissue functions in pigs, without increasing post-weaning diarrhea.

The post-weaning period in pigs is a critical window where nutritional interventions are implemented to prevent post-weaning diarrhea (PWD) and antibiotic use. One common strategy is feeding of low protein diets immediately following weaning. This intervention may reduce protein fermentation and pathogen proliferation, therefore decreasing the incidence of post-weaning diarrhea. These effects may also be mitigated by providing dietary fiber. However, studies examining the role of protein and fiber on gastrointestinal microbiota and metabolism are complicated by the presence of other substrates, including polyphenols and antinutritional factors in complex ingredients. In this study, semi-purified diets formulated to meet nutrient requirements were fed to 40 weaned pigs (n = 10/diet) to examine the effects of high protein (HP), high fiber (HF), or both (HFHP) compared to a control (CON) diet with industry standard crude protein and fiber content. Critical alterations in host metabolism and cecal transcriptome were identified in response to the CON diet. Diets with lower protein levels (CON and HF) induced alteration in transcripts from the serine synthesis pathways and integrated stress response in cecal tissue alongside systemic increases in metabolic pathways related to lysine degradation. High protein diets did not induce increases in gastrointestinal pathogen abundance. These results challenge the practice of feeding low protein diets post-weaning, by demonstrating a detrimental effect on intestinal cell function and muscle accretion. This suggests that with careful ingredient selection, increased dietary protein post-weaning could better pig health and growth compared to a standard diet.

Parvimonas micra forms a distinct bacterial network with oral pathobionts in colorectal cancer patients.

BACKGROUND: Mounting evidence suggests a significant role of the gut microbiota in the development and progression of colorectal cancer (CRC). In particular, an over-representation of oral pathogens has been linked to CRC. The aim of this study was to further investigate the faecal microbial landscape of CRC patients, with a focus on the oral pathogens Parvimonas micra and Fusobacterium nucleatum. METHODS: In this study, 16S rRNA sequencing was conducted using faecal samples from CRC patients (n = 275) and controls without pathological findings (n = 95). RESULTS: We discovered a significant difference in microbial composition depending on tumour location and microsatellite instability (MSI) status, with P. micra, F. nucleatum, and Peptostreptococcus stomatis found to be more abundant in patients with MSI tumours. Moreover, P. micra and F. nucleatum were associated with a cluster of CRC-related bacteria including Bacteroides fragilis as well as with other oral pathogens such as P. stomatis and various Porphyromonas species. This cluster was distinctly different in the control group, suggesting its potential linkage with CRC. CONCLUSIONS: Our results suggest a similar distribution of several CRC-associated bacteria within CRC patients, underscoring the importance of considering the concomitant presence of bacterial species in studies investigating the mechanisms of CRC development and progression.