Effects of fermented milk containing Lacticaseibacillus paracasei strain Shirota on constipation and gut microbiota: A randomised pilot study inVietnam.

IntroductionThis study investigated whether probiotics alleviate Endometriosis (EMs)-related inflammation by modulating the gut microbiota and short-chain fatty acids (SCFAs).MethodsAn endometriosis model was established in SD rats, which were randomly divided into a normal diet group (NCD) and a probiotic group (NCD_Pro), with four rats per group. After a 4-week dietary intervention, serum and fecal samples were collected. Tumor Necrosis Factor (TNF)-α and Interleukin (IL)-6 levels were measured by ELISA, gut microbiota composition was analyzed via 16S rRNA sequencing, and fecal levels of nine SCFAs were quantified using GC–MS.ResultsProbiotic supplementation significantly reduced serum levels of TNF-α and IL-6 (P < 0.05), but did not significantly affect body weight, body length, or lesion volume. Beta diversity analysis revealed significant structural differences in gut microbiota between the two groups (P < 0.05), while alpha diversity showed no significant difference. At the phylum level, probiotic intervention decreased the relative abundance of Firmicutes and increased that of Bacteroidota and Proteobacteria. At the family level, certain bacterial families showed opposite abundance patterns between the two groups. At the genus level, Bifidobacterium and Lactobacillus were significantly enriched in the probiotic group. Microbial co-occurrence network analysis indicated increased node number and connectivity along with enhanced network stability in the probiotic group. SCFA profiling showed decreased levels of butyric acid (BA) and caproic acid (CA), and a significant increase in isocaproic acid (4-MVA) in the probiotic group. Correlation analysis revealed a significant negative association between specific differential microbiota and 4-MVA (r < −0.6, P < 0.01).ConclusionProbiotic intervention alleviates systemic inflammation in endometriosis by reshaping the gut microbiota structure, enhancing microbial network stability, and modulating the SCFA metabolism. Our findings underscore the role of the gut microbiota-metabolism-immunity axis in EMs pathophysiology and point to 4-MVA as a hypothesis-generating candidate metabolite that requires further validation.

Alterations in gut microbiota after colonoscopy have been observed. Moreover, there is limited consensus regarding the impact of the procedure on gut microbiota. We aim to evaluate whether the probiotic can treat gut microbiota and abdominal symptoms disturbance after colonoscopy. A total of 301 participants were randomized into probiotic and placebo groups. The probiotic group received live combined Bacillus Subtilis and Enterococcus Faecium-coated capsules (0.5 g thrice daily for 28 days) postcolonoscopy. The placebo group was given placebo in an identical manner. Fecal samples were collected from participants and symptoms were reported. The intestinal microbiota composition was assessed using 16S rRNA sequencing. Notable differences in α (p = 0.011) and β (p < 0.001) diversity were observed after colonoscopy. Bowel cleansing resulted in the proliferation of Pseudomonas and Klebsiella in the placebo group. However, the probiotic group exhibited a marked enrichment in beneficial probiotics such as Lactobacillales (p = 0.002). Gastrointestinal symptom rating scale (GSRS) showed significant improvements in the probiotic group within the initial week (p = 0.005). Patients in the probiotic group who exhibited symptoms experienced fewer days of abdominal discomfort postcolonoscopy (p = 0.034). Additionally, they exhibited enhanced glucose metabolism (p = 0.040) and a notable increase in Lactobacillales (p = 0.009). In the probiotic group, α and β diversities differed significantly in patients without GSRS improvements, and the concentration of Bacteroides was significantly elevated (p = 0.004). Gut microbiota was altered after colonoscopy, especially the proliferation of potentially pathogenic bacteria. Administering probiotics postcolonoscopy leads to beneficial alterations in gut microbiota and associated metabolic pathways, while abdominal discomfort symptoms were improved early.

Targeting the Gut Microbiota in Coronavirus Disease 2019: Hype or Hope?

Emerging evidence indicates a close relationship between gut microbiota and fatty liver disease. It has been suggested that gut microbiota modulation with probiotics ameliorates fatty liver disease in rodents and humans, yet it remains unclear whether the same results will also be obtained in poultry. The aim of this study was to investigate whether a mixture of probiotics supplemented after hatching can prevent CORT-induced fatty liver disease in broilers, and to determine how such effects, if any, are associated with hepatic de novo lipogenesis and gut microbiota composition. Ninety-six one-day-old green-legged chickens were divided into a control group (CON) and probiotic group (PB). At 28 days of age, fatty liver was induced in 16 broilers that were randomly selected from the CON or PB group. At the end of the experiment, broilers from four groups, (i) the control group (CON), (ii) corticosterone group (CORT), (iii) probiotic group (PB), and (iv) PB plus CORT group (CORT&PB), were slaughtered for sampling and analysis. The results showed that probiotic administration significantly prevented CORT-induced body weight loss (p < 0.05) but did not alleviate the weight loss of immune organs caused by CORT. Compared to CON, the broilers in the CORT group exhibited a significant increase in triglyceride (TG) levels in plasma and liver (p < 0.01), as well as severe hepatocytic steatosis and hepatocellular ballooning, which was accompanied by the upregulation of hepatic lipogenesis gene expression. However, probiotic supplementation markedly decreased the intrahepatic lipid accumulation and steatosis histological score, which was associated with the downregulation of sterol regulatory element-binding protein-1 (SREBP1) and acetyl-CoA carboxylase (ACC) mRNA (p < 0.05) and the expression of its protein (p = 0.06). The cecal microbiota composition was determined by 16S rRNA high-throughput sequencing. The results showed that CORT treatment induced distinct gut microbiota alterations with a decrease in microbial diversity and an increase in Proteobacteria abundance (p < 0.05). In contrast, probiotic supplementation increased the beta diversity, the community richness, and the diversity index (p > 0.05), as well as the abundance of Intestinimonas (p < 0.05). Our results indicate that CORT treatment induced severe fatty liver disease and altered the gut microbiota composition in broilers. However, post-hatching probiotic supplementation had a beneficial effect on alleviating fatty liver disease by regulating lipogenic gene expression and increasing gut microbiota diversity and the abundance of beneficial bacteria. We demonstrate for the first time that the supplementation of probiotics to chicks had a beneficial effect on preventing fatty liver disease through regulating lipogenic gene expression and improving the gut microbial balance. Thus, our results indicate that probiotics are a potential nutritional agent for preventing fatty liver disease in chickens.

BackgroundProbiotics are increasingly applied to prevent and treat a range of infectious, immune related and gastrointestinal diseases. Despite this, the mechanisms behind the putative effects of probiotics are poorly understood. One of the suggested modes of probiotic action is modulation of the endogenous gut microbiota, however probiotic intervention studies in adults have failed to show significant effects on gut microbiota composition. The gut microbiota of young children is known to be unstable and more responsive to external factors than that of adults. Therefore, potential effects of probiotic intervention on gut microbiota may be easier detectable in early life. We thus investigated the effects of a 6 month placebo-controlled probiotic intervention with Bifidobacterium animalis subsp. lactis (BB-12®) and Lactobacillus rhamnosus (LGG®) on gut microbiota composition and diversity in more than 200 Danish infants (N = 290 enrolled; N = 201 all samples analyzed), as assessed by 16S rRNA amplicon sequencing. Further, we evaluated probiotic presence and proliferation by use of specific quantitative polymerase chain reaction (qPCR).ResultsProbiotic administration did not significantly alter gut microbiota community structure or diversity as compared to placebo. The probiotic strains were detected in 91.3% of the fecal samples from children receiving probiotics and in 1% of the placebo treated children. Baseline gut microbiota was not found to predict the ability of probiotics to establish in the gut after the 6 month intervention. Within the probiotics group, proliferation of the strains LGG® and BB-12® in the gut was detected in 44.7% and 83.5% of the participants, respectively. A sub-analysis of the gut microbiota including only individuals with detected growth of the probiotics LGG® or BB-12® and comparing these to placebo revealed no differences in community structure or diversity.ConclusionSix months of probiotic administration during early life did not change gut microbiota community structure or diversity, despite active proliferation of the administered probiotic strains. Therefore, alteration of the healthy infant gut microbiota is not likely to be a prominent mechanism by which these specific probiotics works to exert beneficial effects on host health.Trial registrationNCT02180581. Registered 30 June 2014.

Effect of fermented milk containing Lactobacillus rhamnosus SD11 on oral microbiota of healthy volunteers: A randomized clinical trial

Few studies have examined the effects of smoking habit, the frequency of alcohol drinking, exercise, and fermented milk consumption on defecatory symptoms and gut microbiota composition, and particularly their interactive effects. We examined the effect of these lifestyle factors on bowel movements and gut microbiota composition in 366 healthy Japanese adults by analysis of covariance. Smoking did not affect defecatory symptoms but was negatively correlated with total bacteria and Enterococcus counts. Drinking frequency was significantly positively correlated with a feeling of incomplete evacuation and counts of the Bacteroides fragilis group and Acidaminococcus groups. Exercise frequency tended to be negatively correlated with the Bristol Stool Form Scale score and was significantly negatively correlated with the counts of Enterobacteriaceae and positively correlated with the Prevotella counts in the faeces. The frequency of fermented milk consumption was not significant but tended to be positively correlated with stool frequency. The frequency of fermented milk consumption was significantly positively correlated with the counts of the Atopobium cluster, Eubacterium cylindroides group, Acidaminococcus group, Clostridium ramosum subgroup, and Lactobacillus in the faeces. The frequency of consumption of probiotic Lactobacillus casei-containing fermented milk was significantly positively correlated with stool frequency. The counts of probiotic Lactobacillus casei in the stool was positively correlated with the counts of Bifidobacterium and total Lactobacillus. These results suggest that smoking, alcohol drinking, exercise, and consumption of fermented milk, particularly containing probiotic L. casei, differently affect bowel movements and gut microbiota composition in healthy Japanese adults.

Gastrointestinal symptoms are a common postoperative complication in patients with congenital heart disease (CHD), affecting their postoperative recovery. Probiotic intervention may be a promising therapeutic approach to alleviate postoperative gastrointestinal symptoms. This study aimed to evaluate the potential of Lactobacillus plantarum 24-7 (L. plantarum 24-7) in mitigating postoperative gastrointestinal symptoms and promoting patient recovery. Adult CHD patients scheduled for surgical intervention were recruited. One hundred and twenty patients were randomized and received L. plantarum or placebo intervention twice daily for ten days. Gastrointestinal symptoms were assessed utilizing the Gastrointestinal Symptom Rating Scale (GSRS). Various postoperative variables were analyzed across both groups. Alterations in gut microbiota were evaluated through 16S rRNA sequencing. 112 patients completed the study, with 55 in the probiotic group and 57 in the placebo group. While the disparity in overall postoperative GSRS scores between the two groups did not reach statistical significance (P = 0.067), marked differences were observed in bloating (P = 0.004) and hard stool (P = 0.030) scores. Furthermore, individuals within the probiotic group exhibited lower postoperative neutrophil counts (P = 0.007) and concurrently higher lymphocyte counts (P = 0.001). Variations in the diversity and composition of postoperative gut microbiota were discerned between the probiotic and placebo groups. Remarkably, no probiotic-related adverse events were documented. Supplementation with L. plantarum was well-tolerated and demonstrated partial efficacy in ameliorating gastrointestinal symptoms in postoperative CHD patients. Modulating the gut microbiota may be a potential mechanism by which L. plantarum exerts clinical benefits.

BACKGROUNDHealth maintenance in elderly houses includes management of the gut microbiota and the environment. Lacticaseibacillus paracasei Shirota (LcS) is a probiotic strain that positively affects the human gut. However, the evidence of its effects on the Indonesian population remains limited.AIMTo investigate the effect of LcS-fermented milk on the gut microbiota and environment of Indonesian elderly houses.METHODSThis double-blind, randomized, placebo-controlled trial involved 112 participants from Indonesian elderly houses, spanning a 2-week baseline and 24-week treatment. Participants were randomly assigned to probiotic or placebo groups, consuming fermented milk with or without LcS (> 6.5 × 109 colony-forming units). Fecal samples were collected every three months. Gut microbiota analysis was performed using 16S rRNA gene sequencing and reverse transcription quantitative polymerase chain reaction, while gut environment was assessed by measuring fecal organic acids, amino acid metabolites, and stool frequency.RESULTSAnalyses of 16S rRNA gene sequence data at the 3-month period revealed increased Bifidobacterium and Succinivibrio and decreased Rikenellaceae RC9 gut group in the probiotic group. These shifts were associated with significant differences in β-diversity metrics. The change in Bifidobacterium was confirmed by reverse transcription quantitative polymerase chain reaction, demonstrating higher abundance in the probiotic group than in the placebo group (8.5 ± 1.1 vs 8.0 ± 1.1, log10 bacterial cells/g; P = 0.044). At 6-month period, the differences in Succinivibrio and Rikenellaceae RC9 gut group persisted. The probiotic group showed higher butyrate levels than the placebo group at the 6-month period (5.04 ± 3.11 vs 3.95 ± 2.89, μmol/g; P = 0.048). The effect on amino acid metabolites and stool frequency was not significant.CONCLUSIONDaily intake of LcS positively affects the gut microbiota and environment of people living in Indonesian elderly houses.

To investigate the effect of metformin on gut microbiota imbalance in patients with type 2 diabetes mellitus (T2DM), and the value of probiotic supplementation. A total of 84 newly diagnosed T2DM patients were randomly divided into probiotics group, metformin group, and control group, with 28 patients in each group. The blood glucose control, islet function, gut microbiota, and inflammatory factors were compared between three groups. After 3 months of treatment, fasting plasma glucose (FPG), 2-h postprandial plasma glucose (2-h PG), and glycosylated hemoglobin A1c (HbA1c) were evidently decreased in both probiotics and metformin groups (P < 0.05) and were lower than that in the control group prior to treatment. Besides, FPG, 2-h PG, and HbA1c were lower in the metformin group than that in the control group. FPG, 2-h PG, and HbA1c were further lower in the probiotic group than in the metformin group (P < 0.05). Fasting insulin (FINS) and islet β cell (HOMA-β) -function were dramatically increased in the same group (P < 0.05), while insulin-resistant islet β cells (HOMA-IR) were significantly lower in the same group (P < 0.05); FINS and HOMA-β were significantly higher, while HOMA-IR was significantly lower (P < 0.05) in both groups than in the control group prior to treatment. HOMA-IR was also lower in the probiotic group than in the metformin group after treatment (P < 0.05); the number of lactobacilli and bifidobacteria increased (P < 0.05) in both probiotic and metformin groups than in the control group prior to treatment, and the number of Enterobacteriaceae and Enterococcus was lower in the control group prior to treatment (P < 0.05). In addition, the number of lactobacilli and bifidobacteria was higher and the number of enterobacteria and enterococci was lower in the probiotic group than that in the metformin group after treatment, and the differences were statistically significant (P < 0.05). Lipopolysaccharide (LPS), interleukin 6 (IL-6), and C-reactive protein (CRP) levels were lower in both probiotic and metformin groups (P < 0.05). The serum LPS, IL-6, and CRP levels were lower in both probiotic and metformin groups, compared to the control group prior to the treatment (P < 0.05). Metformin while treating T2DM assists in improving the imbalance of gut microbiota.

Introduction and Objective: Metformin, the first-line treatment for type 2 diabetes, exerts antidiabetic effects partly through gut microbiota modulation. However, it can also increase Escherichia species capable of inducing endotoxemia via lipopolysaccharide (LPS). This study investigated metabolic endotoxemia, represented by LPS-binding protein (LBP) and its antagonist bactericidal/permeability-increasing protein (BPI), in relation to therapeutic responses to metformin-based therapy. Methods: We recruited 87 subjects from a cohort of type 2 diabetes treated at a medical center in southern Taiwan (from 2016 to 2024). Subjects were stratified into three groups: (1) good control on metformin monotherapy (GM, HbA1c ≤7%), (2) good control with metformin plus dipeptidyl peptidase-4 inhibitors (DPP4i) (GC, HbA1c ≤7% after failure on metformin alone), and (3) poor control on metformin or metformin plus DPP4i (PC, HbA1c &amp;gt;7% but ≤9%). Plasma LBP and BPI levels were measured, and gut microbiota compositions were analyzed via 16S rRNA sequencing. Results: LBP levels were significantly higher in PC compared to GM, in parallel with the higher HOMA-IR in PC. Although BPI levels were similar across groups, elevated LBP in PC indicated greater metabolic endotoxemia. LBP also showed negative correlations with HDL-cholesterol and positive correlations with triglycerides, GPT, CRP, and HOMA-IR. Gut microbiota diversity (Shannon index, representing community evenness) was reduced in GM, with distinct clustering across groups by unweighted UniFrac analysis. Conclusion: Elevated LBP in poorly controlled diabetes highlighted the role of metabolic endotoxemia contributing to insulin resistance. Reduced gut microbiota diversity was observed in type 2 diabetes with durability to metformin monotherapy, suggesting microbial shifts critical to maintaining metformin efficacy. Further analysis of specific microbial changes is warranted. Disclosure W. Hung: None. W. Hung: None. Funding National Science and Technology Council (112-2314-B-037-070-)

Increased evidence shows that gut microbiota acts as the primary regulator of the liver; however, its role in sepsis-related liver injury (SLI) in the elderly is unclear. This study assessed whether metformin could attenuate SLI by modulating gut microbiota in septic-aged rats. Cecal ligation and puncture (CLP) was used to induce SLI in aged rats. Fecal microbiota transplantation (FMT) was used to validate the roles of gut microbiota in these pathologies. The composition of gut microbiota was analysed by 16S rRNA sequencing. Moreover, the liver and colon tissues were analysed by histopathology, immunofluorescence, immunohistochemistry, and reverse transcription polymerase chain reaction (RT–PCR). Metformin improved liver damage, colon barrier dysfunction in aged SLI rats. Moreover, metformin improved sepsis-induced liver inflammation and damage under gut microbiota. Importantly, FMT assay showed that rats gavaged with faeces from metformin-treated SLI rats displayed less severe liver damage and colon barrier dysfunctions than those gavaged with faeces from SLI rats. The gut microbiota composition among the sham-operated, CLP-operated and metformin-treated SLI rats was different. In particular, the proportion of Klebsiella and Escherichia_Shigella was higher in SLI rats than sham-operated and metformin-treated SLI rats; while metformin could increase the proportion of Bifidobacterium, Muribaculaceae, Parabacteroides_distasonis and Alloprevitella in aged SLI rats. Additionally, Klebsiella and Escherichia_Shigella correlated positively with the inflammatory factors in the liver. Our findings suggest that metformin may improve liver injury by regulating the gut microbiota and alleviating colon barrier dysfunction in septic-aged rats, which may be an effective therapy for SLI.

Sarcopenia, characterized by reduced skeletal muscle mass and function, is a common geriatric condition that impairs mobility and quality of life. Its causes include neuroendocrine dysregulation, chronic inflammation, malnutrition, and gut microbiota imbalance. The gut microbiota influences muscle metabolism and function via the gut-muscle axis, and aerobic exercise has been shown to improve both gut microbiota composition and muscle function. This study explores whether aerobic exercise can alleviate sarcopenia induced by gut microbiota dysbiosis through the gut-muscle axis, offering a basis for exercise interventions. The study employed the senescence-accelerated mouse strain P8 (SAMP8) model. Gut microbiota dysbiosis was induced via a one-week intraperitoneal injection of a broad-spectrum antibiotic cocktail (ABX). Eight-week-old male SAMP8 mice were divided into four groups: control (CON), ABX-treated (ABX), exercise-trained (EXE), and ABX-treated with exercise (ABX+EXE). The EXE and ABX+EXE groups underwent an 8-week aerobic exercise program with progressively increasing intensity. Post-intervention assessments included skeletal muscle mass (quadriceps and gastrocnemius weights), muscle strength (hanging and grip strength tests), muscle fiber type (HE staining and immunohistochemistry), oxidative stress markers (malondialdehyde and superoxide dismutase), gut microbiota composition (16S rRNA sequencing), intestinal barrier function (serum diamine oxidase and D-lactate levels), and neuromuscular junction protein expression (Western blot). Data were analyzed using SPSS 26.0, expressed as mean ± SD, and compared using one-way ANOVA. ABX treatment significantly reduced gut microbiota diversity (P &lt; 0.01), disrupted intestinal barrier function (elevated serum diamine oxidase and D-lactate, P&lt;0.05), and exacerbated sarcopenia (decreased muscle mass and strength, P &lt; 0.01). Aerobic exercise significantly improved muscle mass (P &lt; 0.01) and strength (P &lt; 0.01) in ABX-treated mice, increased fast-twitch muscle fiber proportion (P &lt; 0.05), and reduced oxidative stress (P &lt; 0.05). Exercise also modulated gut microbiota (increased diversity, P &lt; 0.01), enhanced intestinal barrier function (decreased diamine oxidase and D-lactate, P &lt; 0.05), and promoted neuromuscular junction protein expression (P &lt; 0.05). This study elucidates the mechanisms by which aerobic exercise ameliorates sarcopenia via the gut-muscle axis, underscoring the role of gut microbiota. However, the small sample size and single animal model limit the findings' generalizability. Future research should expand the sample size and incorporate diverse models or clinical studies to validate this mechanism. This study supports aerobic exercise as a non-pharmacological intervention for sarcopenia, potentially improving quality of life in the elderly.

Exploring the gut-kidney axis: Berberine's role in alleviating chronic kidney disease through microbiota and short-chain fatty acids.

Autoimmune thyroid diseases (AITDs) are among the most prevalent organ-specific autoimmune disorders, with thyroid hormones playing a pivotal role in the gastrointestinal system's structure and function. Emerging evidence suggests a link between AITDs and the gut microbiome, which is a diverse community of organisms that are essential for digestion, absorption, intestinal homeostasis, and immune defense. Recent studies using 16S rRNA and metagenomic sequencing of fecal samples from AITD patients have revealed a significant correlation between a gut microbiota imbalance and the severity of AITDs. Progress in animal models of autoimmune diseases has shown that intervention in the gut microbiota can significantly alter the disease severity. The gut microbiota influences T cell subgroup differentiation and modulates the pathological immune response to AITDs through mechanisms involving short-chain fatty acids (SCFAs), lipopolysaccharides (LPSs), and mucosal immunity. Conversely, thyroid hormones also influence gut function and microbiota composition. Thus, there is a bidirectional relationship between the thyroid and the gut ecosystem. This review explores the pathogenic mechanisms of the gut microbiota and its metabolites in AITDs, characterizes the gut microbiota in Graves' disease (GD) and Hashimoto's thyroiditis (HT), and examines the interactions between the gut microbiota, thyroid hormones, T cell differentiation, and trace elements. The review aims to enhance understanding of the gut microbiota-thyroid axis and proposes novel approaches to mitigate AITD severity through gut microbiota modulation.