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This article summarises the state of the science on the role of the gut microbiota (GM) in diabetes from a recent international expert forum organised by Diabetes, Diabetes Care, and Diabetologia, which was held at the European Association for the Study of Diabetes 2023 Annual Meeting in Hamburg, Germany. Forum participants included clinicians and basic scientists who are leading investigators in the field of the intestinal microbiome and metabolism. Their conclusions were as follows: (1) the GM may be involved in the pathophysiology of type 2 diabetes, as microbially produced metabolites associate both positively and negatively with the disease, and mechanistic links of GM functions (e.g. genes for butyrate production) with glucose metabolism have recently emerged through the use of Mendelian randomisation in humans; (2) the highly individualised nature of the GM poses a major research obstacle, and large cohorts and a deep-sequencing metagenomic approach are required for robust assessments of associations and causation; (3) because single time point sampling misses intraindividual GM dynamics, future studies with repeated measures within individuals are needed; and (4) much future research will be required to determine the applicability of this expanding knowledge to diabetes diagnosis and treatment, and novel technologies and improved computational tools will be important to achieve this goal.

BackgroundGut microbes produce short-chain fatty acids (SCFAs), which are associated with broad health benefits. However, it is not fully known how diet and/or the gut microbiome could be modulated to improve SCFA production.ObjectivesThe objective of this study was to identify dietary, inflammatory, and/or microbiome predictors of SCFAs in a cohort of healthy adults.MethodsSCFAs were measured in fecal and plasma samples from 359 healthy adults in the United States Department of Agriculture Nutritional Phenotyping Study. Habitual and recent diet was assessed using a food frequency questionnaire and automated self-administered 24-h dietary assessment tool dietary recalls. Markers of systemic and gut inflammation were measured in fecal and plasma samples. The gut microbiome was assessed using shotgun metagenomics. Using statistics and machine learning, we determined how the abundance and composition of SCFAs varied with measures of diet, inflammation, and the gut microbiome.ResultsWe show that fecal pH may be a good proxy for fecal SCFA abundance. A higher healthy eating index for a habitual diet was associated with a compositional increase in fecal butyrate relative to acetate and propionate. SCFAs were associated with markers of subclinical gastrointestinal (GI) inflammation. Fecal SCFA abundance was inversely related to plasma lipopolysaccharide-binding protein. When we analyzed hierarchically organized diet and microbiome data with taxonomy-aware algorithms, we observed that diet and microbiome features were far more predictive of fecal SCFA abundances compared to plasma SCFA abundances. The top diet and microbiome predictors of fecal butyrate included potatoes and the thiamine biosynthesis pathway, respectively.ConclusionsThese results suggest that resistant starch in the form of potatoes and microbially produced thiamine provide a substrate and essential cofactor, respectively, for butyrate synthesis. Thiamine may be a rate-limiting nutrient for butyrate production in adults. Overall, these findings illustrate the complex biology underpinning SCFA production in the gut. This trial was registered at clinicaltrials.gov as NCT02367287.

The complex role of the gut microbiome in the pathogenesis of gastrointestinal (GI) disorders is an emerging area of research, and there is considerable interest in understanding how diet can alter the composition and function of the microbiome. Prebiotics and probiotics have been shown to beneficially modulate the gut microbiome, which underlies their potential for benefit in GI conditions. Formulating specific recommendations for the public regarding these dietary supplements has been difficult due to the significant heterogeneity between strains, doses, and duration of treatment investigated across studies, as well as safety concerns with administering live organisms. This review aims to summarize the existing evidence for the use of prebiotics and probiotics in various GI disorders, paying special attention to strain-specific effects that emerged and any adverse effects noted.

Gut microbiota modulates host physiology and pathophysiology through the production of microbial metabolites. Diet is a crucial factor in shaping the microbiome, and gut microbes interact with the host by producing beneficial or detrimental diet-derived microbial metabolites. Evidence from our lab and others indicates that the interaction between diet and gut microbes plays a pivotal role in modulating vascular health. Diet-derived microbial metabolites such as short-chain fatty acids and metabolites of phenolic acids improve vascular health, whereas trimethylamine oxide and certain amino acid-derived microbial metabolites impair the vasculature. These metabolites have been shown to regulate blood pressure, vascular inflammation, and atherosclerosis by acting on multiple targets. Nonetheless, there are substantial gaps in knowledge within this field. The microbial enzymes essential for the production of diet-derived metabolites, the role of the food matrix in regulating the bioavailability of metabolites, and the structure-activity relationships between metabolites and biomolecules in the vasculature are largely unknown. Potential diet-derived metabolites to improve vascular health can be identified through future studies that investigate the causal relationship between dietary components, gut microbes, diet-derived metabolites, and vascular health by using radiolabeled compounds, metabolomics, transcriptomics, and proteomics techniques. [ABSTRACT FROM AUTHOR]

Citrus polyphenols can modulate gut microbiota and such bi-directional interaction that can yield metabolites such as short-chain fatty acids (SCFAs) to aid in gut homeostasis. Such interaction provides citrus polyphenols with powerful prebiotic potential, contributing to guts' health status and metabolic regulation. Citrus polyphenols encompass unique polymethoxy flavonoids imparting non-polar nature that improve their bioactivities and ability to penetrate the blood-brain barrier. Green extraction technology targeting recovery of these polyphenols has received increasing attention due to its advantages of high extraction yield, short extraction time, low solvent consumption, and environmental friendliness. However, the low bioavailability of citrus polyphenols limits their applications in extraction from citrus by-products. Meanwhile, nano-encapsulation technology may serve as a promising approach to improve citrus polyphenols' bioavailability. As citrus polyphenols encompass multiple hydroxyl groups, they are potential to interact with bio-macromolecules such as proteins and polysaccharides in nano-encapsulated systems that can improve their bioavailability. This multifaceted review provides a research basis for the green and efficient extraction techniques of citrus polyphenols, as well as integrated mechanisms for its anti-inflammation, alleviating metabolic syndrome, and regulating gut homeostasis, which is more capitalized upon using nano-delivery systems as discussed in that review to maximize their health and food applications. [ABSTRACT FROM AUTHOR]

Rationale: Stressors play a critical role in the progression of irritable bowel syndrome (IBS). Heterogenous stress causes alterations in our bowel movements which can further cause anxiety and depression-like symptoms, decreasing the ability of individuals worldwide to function in social, academic, and employment settings. Objectives: This study was aimed to investigate the effect of orally administered Nigella sativa (0.2 mL/kg b.wt.) seed oil (NSSO) on stress-induced IBS, anxiety, and depression-like symptoms in Wistar rats. Methods: In the present study, modelling IBS induced anxiety and depression-like symptoms in rodents have been employed to correlate the pathophysiological mechanisms behind this disorder. Moreover, evaluation of ameliorative potential of traditionally used NSSO in IBS was also carried out. Results: Present investigation indicated that acute stress of 1.5 h daily for 20 days induced hyper cortisol, gastrointestinal (GI) hypermotility, diarrhoea, altered levels of short chain fatty acids (SCFAs), and inflammation which are common symptoms of IBS. Furthermore, depression and anxiety-like symptoms were validated in test groups by various behavioral tests and decreased levels of 5-HT-Transporter mRNA gene expression, which are clear indicators of cognitive impairment. Conclusions: It is possible that these IBS-like symptoms may have contributed to the pathogenesis of cognitive deficits and depression. However, the anti-oxidative, anti-inflammatory, anti-spasmodic, and possibly the anti-anxiolytic properties of NSSO helped in the mitigation of altered gut-brain axis. Because the concurrent treatment of NSSO alleviated the symptoms of modified GI function and consequently, the anxious & depressive behavior of the animals. Overall, this research explored the protective efficacy of NSSO against stress-induced IBS and depression-like symptoms, shedding light on the potential of this natural compound as a therapeutic option in the field of gastroenterology and psychiatry. [ABSTRACT FROM AUTHOR]

Lactiplantibacillus plantarum Dad-13, Lactiplantibacillus plantarum FNCC-0250 and Lacticaseibacillus paracasei GMRMP-001 are probiotics strain isolated from Indonesian local and traditional fermented foods. This study aims to evaluate the administration of multi-strain probiotics at dose of 109 CFU/mL/day for 14 days against the diarrhea-causing bacteria Escherichia coli FNCC-0091 at a dose of 1011 CFU/mL/day. Thirty rats were randomized and the divided into 5 groups, including control group, skim milk group, single-strain group, multi-strain group and E. coli group. Antibacterial activity was analyzed in vitro, feed intake, body weight were analyzed, microbial analysis was carried out on feces and cecum, short chain fatty acids were analyzed and intestinal morphology was measured. The result showed that the single-strain and multi-strain inhibition zone in in vitro test produces a very strong inhibitory potential (> 9 mm). The number of L. plantarum and L. paracasei increased and the number of E. coli decreased significantly in the feces and cecum of Rat indicating the survival rate of the probiotic bacteria in the digestive tract and their ability to fight pathogenic bacteria. The concentration of acetic acid, propionic acid and butyric acid compounds also increased, indicating that the digestive tract is at a low pH so that it can inhibit the growth of pathogenic bacteria in rats. In addition, consumption of multi-strain probiotics does not have a negative effect on intestinal morphology. The conclusion is that multi-strain probiotics are able to inhibit pathogenic bacteria in vivo and in vitro. [ABSTRACT FROM AUTHOR]

BACKGROUND: Quercitrin is a dietary flavonoid widely found in plants with various physiological activities. However, whether quercitrin alters gut microbiota in vivo is not well understood. The aim of this study was to investigate metabolism of quercitrin in the colon and its regulation on gut microbiota in mice. RESULTS: Herein, 22 flavonoids related to quercitrin metabolism were identified based on ultra‐performance liquid chromatography‐electrospray ionization‐tandem mass spectrometry (UPLC‐ESI‐MS/MS). Gas chromatography and 16S rDNA gene sequencing were used to investigate short‐chain fatty acid (SCFA) content and diversity of composition of gut microbiota, respectively. The results showed that quercitrin significantly alters the beta‐diversity of the gut microbiota, probiotics such as Akkermansia and Lactococcus were significantly increased, and the production of propanoate, isovalerate and hexanoate of the quercitrin group were enhanced significantly. The Spearman's association analysis provided evidence that Gardnerella and Akkermansia have obvious correlations with most of quercitrin metabolites and SCFAs. CONCLUSION: Quercitrin and its metabolites in the colon altered the structure of the mice gut microbiota and increased the content of SCFAs. Our experiments provide valuable insights into quercitrin research and application. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Objective: The objective was to investigate growth performance, antioxidant enzyme activity, intestinal morphology, immune cell distribution, short chain fatty acid (SCFA) profile, and microbiota in broiler chickens fed a diet containing Lacticaseibacillus paracasei NSMJ15. Methods: A total of 120 1-day-old Ross 308 male broilers were allocated to 2 dietary treatments in a randomized complete block design. A control group was fed a corn-soybean meal control diet, and an NSMJ15-supplemented group was fed a control diet supplemented with 1 g/kg L. paracasei NSMJ15 at the expense of cornstarch. Each dietary treatment had 6 replicates with 10 birds per cage. Growth performance was recorded on day 9. On day 10, one bird representing median body weight was selected to collect serum for antioxidant enzyme activity, jejunal tissue for immune cell isolation and morphometric analysis, and cecal digesta for 16S rRNA gene sequencing and SCFA analysis. Results: Supplementation of L. paracasei NSMJ15 did not affect growth performance, serum antioxidant enzyme activity, and jejunal histomorphology compared to the control group. In the NSMJ15-supplemented group, the population of CD3+CD4+CD8− T cells increased (p = 0.010), while the population of CD3+CD8+TCRγδ+ T cells decreased (p = 0.022) compared to the control group. The L. paracasei NSMJ15 supplementation decreased (p = 0.022) acetate concentration in the cecal digesta compared to the control group. The 16S rRNA gene sequencing analysis showed that NSMJ15-supplemented group differentially expressed (p<0.05) 10 more amplicon sequence variants compared to control group without affecting alpha and beta diversity indices of the cecal microbiota. Genera Mediterraneibacter and Negativibacillus were positively (p<0.05) correlated with CD4+ T cells, while genera Gemmiger, Coprococcus, Sellimonas, Massilimicrobiota, and Blautia were negatively (p<0.05) correlated with SCFA concentration. Conclusion: The results of the present study suggest dietary L. paracasei NSMJ15 supplementation may increase percentage of CD4+ T cells and decrease acetate concentration in broiler chickens by increasing the differential expression of specific microbial genera. [ABSTRACT FROM AUTHOR]

Objective: The current study investigated the effects of mulberry 1-deoxynijirimycin (DNJ) on the digestion ability, intestinal morphology, and intestinal barrier of rabbits. Methods: A total of 36 New Zealand White rabbits (male) about 45 days old (mean body weight of 1.05±0.04 kg) were reared and commercial diets were employed, and afterwards divided into three groups (n = 12) with different levels of DNJ extract additive in feed: T0 (0 g/kg), T1 (0.35 g/kg), T2 (0.7 g/kg) for 28 d. Results: The results demonstrated that T2 decreased the average daily gain (p<0.05). T1 and T2 decreased villus height and inflammatory factor levels as compared with T0 (p<0.05). DNJ significantly decreased the content of valeric acid (p<0.05). The content of acetic acid, propionic acid, iso butyric acid, iso valeric acid in T1 were higher than those in T0 and T2 (p<0.05). The content of butyric acid in T2 was lower than it in T0 and T1 (p<0.05). The content of caproic acid was firstly improved then reduced as the DNJ concentration improved (p<0.05). T2 significantly increased the abundance of dgA-11_gut_group and Christensenellaceae_R-7_group while decreased Bacteroide and Ralstonia as compared with T0 (p<0.05). Compared with T0, T1, and T2 significantly improved the gene expression of JAM2, JAM3, mucin4, mucin6 (p<0.05), T1 significantly decreased the expression of occluding while T2 significantly increased (p<0.05), T2 significantly increased the expression of claudin1 and claudin2 (p<0.05). Conclusion: DNJ at high level changed microbiome compositions, inhibited inflammation, and improved intestinal barrier while it decreased the growth performance and shorted villus height in rabbit jejunum by regulating short chain fatty acid compositions in rabbits. [ABSTRACT FROM AUTHOR]

Resistant starch, also known as anti-digestion enzymatic starch, which cannot be digested or absorbed in the human small intestine. It can be fermented in the large intestine into short-chain fatty acids (SCFAs) and metabolites, which are advantageous to the human body. Starches can classify as rapidly digestible starch (RDS), slowly digestible starch (SDS), and resistant starch (RS), which possess high thermal stability, low water holding capacity, and emulsification characteristics. Resistant starch has excellent physiological functions such as stabilizing postprandial blood glucose levels, preventing type II diabetes, preventing intestinal inflammation, and regulating gut microbiota phenotype. It is extensively utilized in food processing, delivery system construction, and Pickering emulsion due to its processing properties. The resistant starches, with their higher resistance to enzymatic hydrolysis, support their suitability as a potential drug carrier. Therefore, this review focuses on resistant starch with structural features, modification characteristics, immunomodulatory functions, and delivery system applications. The objective was to provide theoretical guidance for applying of resistant starch to food health related industries. [ABSTRACT FROM AUTHOR]

Context: Diabetic kidney disease (DKD) affects nearly 40% of diabetic patients, often leading to end-stage renal disease that requires renal replacement therapies, such as dialysis and transplantation. the gut microbiota, an integral aspect of human evolution, plays a crucial role in this condition. Traditional chinese medicine (TCM) has shown promising outcomes in ameliorating DKD by addressing the gut microbiota. Objective: this review elucidates the modifications in gut microbiota observed in DKD and explores the impact of TCM interventions on correcting microbial dysregulation. Methods: we searched relevant articles from databases including web of Science, PubMed, ScienceDirect, wiley, and Springer Nature. the following keywords were used: diabetic kidney disease, diabetic nephropathy, gut microbiota, natural product, TCM, chinese herbal medicine, and chinese medicinal herbs. Rigorous criteria were applied to identify high-quality studies on tcM interventions against DKD. Results: Dysregulation of the gut microbiota, including Lactobacillus, Streptococcus, and Clostridium, has been observed in individuals with DKD. Key indicators of microbial dysregulation include increased uremic solutes and decreased short-chain fatty acids. various TCM therapies, such as formulas, tablets, granules, capsules, and decoctions, exhibit unique advantages in regulating the disordered microbiota to treat DKD. Conclusion: this review highlights the importance of targeting the gut-kidney axis to regulate microbial disorders, their metabolites, and associated signaling pathways in DKD. The Qing-Re-Xiao-Zheng formula, the Shenyan Kangfu tablet, the Huangkui capsule, and the Bekhogainsam decoction are potential candidates to address the gut-kidney axis. TCM interventions offer a significant therapeutic approach by targeting microbial dysregulation in patients with DKD. [ABSTRACT FROM AUTHOR]

The beneficial effects of gut flora on reducing nerve cell apoptosis and inflammation and improving epilepsy (EP) symptoms have been reported, but the specific mechanism of action is still unclear. A series of in vitro and in vivo experiments revealed the relationship between gut microbiota metabolites and the cGAS/STING axis and their role in EP. These results suggest that antibiotic-induced dysbiosis of gut microbiota exacerbated epileptic symptoms, probiotic supplements reduced epileptic symptoms in mice. Antibiotics and probiotics altered the diversity and composition of gut microbiota. The changes in gut bacteria composition, such as in the abundance of Firmicutes, Bacteroidetes, Lactobacillus and Ruminococcus, were associated with the production of short-chain fatty acids (SCFA) in the gut. The concentrations of propionate, butyrate and isovalerate were changed after feeding antibiotics and probiotics, and the increase in butyrate levels reduced the expression of cGAS/STING in nerve cell further reduced Bax protein expression. The reduction of Bax protein attenuated the hippocampal neuron cell apoptosis in PTZ-induced EP and EP progression. Our findings provide new insights into the roles and mechanisms of action of the gut microbiota in attenuating EP symptoms and progression. [ABSTRACT FROM AUTHOR]

The gut microbiome may be involved in the occurrence of dementia primarily through the molecular mechanisms of producing bioactive molecules and promoting inflammation. Epidemiological evidence linking gut microbiome molecules and inflammatory markers to dementia risk has been mixed, and the intricate interplay between these groups of biomarkers suggests that their joint investigation in the context of dementia is warranted. We aimed to simultaneously investigate the association of circulating levels of selected gut microbiome molecules and inflammatory markers with dementia risk. This case–cohort epidemiological study included 805 individuals (83 years, 66% women) free of dementia at baseline. Plasma levels of 19 selected gut microbiome molecules comprising lipopolysaccharide, short-chain fatty acids, and indole-containing tryptophan metabolites as well as four inflammatory markers measured at baseline were linked to incident all-cause (ACD) and Alzheimer's disease dementia (AD) in binary outcomes and time-to-dementia analyses. Independent of several covariates, seven gut microbiome molecules, 5-hydroxyindole-3-acetic acid, indole-3-butyric acid, indole-3-acryloylglycine, indole-3-lactic acid, indole-3-acetic acid methyl ester, isobutyric acid, and 2-methylbutyric acid, but no inflammatory markers discriminated incident dementia cases from non-cases. Furthermore, 5-hydroxyindole-3-acetic acid (hazard ratio: 0.58; 0.36–0.94, P = 0.025) was associated with time-to-ACD. These molecules underpin gut microbiome-host interactions in the development of dementia and they may be crucial in its prevention and intervention strategies. Future larger epidemiological studies are needed to confirm our findings, specifically in exploring the repeatedly measured circulating levels of these molecules and investigating their causal relationship with dementia risk. [ABSTRACT FROM AUTHOR]

Probiotics are widely recognized for their ability to prevent and therapy antibiotic-associated diarrhea (AAD). This study was designed to evaluate Lactiplantibacillus plantarum ELF051 ability to prevent colon inflammation and its effect on gut microbial composition in a mouse model of AAD. The mice were intragastrically administered triple antibiotics for 7 days and then subjected to L. plantarum ELF051 for 14 days. The administration of L. plantarum ELF051 ameliorated the pathological changes in the colon tissue, downregulated interleukin (IL)-1β and tumor necrosis factor (TNF)-α, and upregulated IL-10, and increased the intestinal short-chain fatty acids (SCFAs) level. Lactiplantibacillus plantarum ELF051 also regulated the Toll-like receptor/myeloid differentiation primary response 88/nuclear factor kappa light chain enhancer of activated B cells (TLR4/MyD88/NF-κB) and the phosphatidylinositol 3-kinase/protein kinase B/ NF-κB (PI3K/AKT/ NF-κB) inflammatory signaling pathways. 16S rRNA analyses showed that L. plantarum ELF051 increased the abundance and diversity of gut bacteria, restoring gut microbiota imbalance. A Spearman's rank correlation analysis showed that lactobacilli are closely associated with inflammatory markers and SCFAs. This work demonstrated that L. plantarum ELF051 can attenuate antibiotic-induced intestinal inflammation in a mouse AAD model by suppressing the pro-inflammatory response and modulating the gut microbiota. [ABSTRACT FROM AUTHOR]

Background: Gastrectomy is one of the main treatment modalities for gastric cancer (GC) and induces pathophysiological changes that significantly affect patients' postoperative recovery. In this study, we investigated the relationships between altered insulin resistance (IR), inflammation, and gut microbiota associated with gastrectomy. Patients and Methods: This study was a single-center prospective cohort investigation involving 60 patients with GC who underwent gastrectomy between May 2023 and April 2024. Monitoring encompassed IR, inflammation, and nutrition-related markers via blood assays, while gut microbiota analysis employed high-throughput sequencing, and short-chain fatty acids (SCFAs) were examined through targeted metabolomics. The study is registered under the number ChiCTR2300075653. Results: The patients exhibited a significant increase in post-gastrectomy IR markers (P < 0.001), accompanied by elevated inflammation markers (P < 0.001), and also showed decreased nutrition-related indicators (P < 0.001). Notable alterations were observed in the gut microbiota, including reductions in Bifidobacterium and Faecalibacterium, an increase in Streptococcus, and a noteworthy decrease in fecal butyrate. Patients with postoperative IR exhibited poorer inflammation markers (P < 0.05), nutritional indicators (P < 0.05), and postoperative recovery parameters (P < 0.05). Furthermore, significant negative correlations were observed between IR and Bifidobacterium, Faecalibacterium, as well as butyrate. Conclusions: Patients with GC post-gastrectomy displayed heightened IR, exacerbated inflammation, and compromised nutritional status. Disturbed gut microbiota and reduced fecal butyrate were observed. Gut microbiota and metabolite butyrate production may be predictors of postoperative IR and short-term outcomes in patients with GC. [ABSTRACT FROM AUTHOR]

Gut microbiota dysbiosis is associated with inflammation and many chronic diseases. The present study investigated the efficacy of mung bean seed coat extract (MSE) on gut microbiome modulation and the attenuation of inflammatory markers in high-fat diet (HFD)-fed rats. The high-throughput sequencing of the 16S rRNA showed the low dose (0.3%) of MSE improved HFD-induced gut microbiota dysbiosis and enhanced the gut microbiota richness. The low dose of MSE showed a significant increase in the abundance of beneficial bacteria, particularly Blautia and Lactobacillus, and decreased abundance of potentially pathogenic bacteria (Escherichia-Shigella). The low dose of MSE also significantly decreased IL-1β mRNA expression and tended to lower IL-6, TNF-α, and LPS levels. In conclusion, this study suggested that the MSE could modulate gut microbiota and reduce inflammatory responses in HFD-fed rats and this indicated the potential health properties of mung bean seed coat. This research provides informative support for the application of mung bean seed coat as functional ingredients. [ABSTRACT FROM AUTHOR]

Background: Human Immunodeficiency Virus (HIV)/Simian Immunodeficiency Virus (SIV) infection is associated with significant gut damage, similar to that observed in patients with inflammatory bowel disease (IBD). This pathology includes loss of epithelial integrity, microbial translocation, dysbiosis, and resultant chronic immune activation. Additionally, the levels of all-trans-retinoic acid (atRA) are dramatically attenuated. Data on the therapeutic use of anti-α4β7 antibodies has shown promise in patients with ulcerative colitis and Crohn's disease. Recent evidence has suggested that the microbiome and short-chain fatty acid (SCFA) metabolites it generates may be critical for anti-α4β7 efficacy and maintaining intestinal homeostasis. Materials and Methods: To determine whether the microbiome contributes to gut homeostasis after anti-α4β7 antibody administered to SIV-infected rhesus macaques, faecal SCFA concentrations were determined, 16S rRNA sequencing was performed, plasma viral loads were determined, plasma retinoids were measured longitudinally, and gut retinoid synthesis/response gene expression was quantified. Results: Our results suggest that anti-α4β7 antibody facilitates the return of retinoid metabolism to baseline levels after SIV infection. Furthermore, faecal SCFAs were shown to be associated with retinoid synthesis gene expression and rebound viral loads after therapy interruption. Conclusions: Taken together, these data demonstrate the therapeutic advantages of anti-α4β7 antibody administration during HIV/SIV infection and that the efficacy of anti-α4β7 antibody may depend on microbiome composition and SCFA generation. [ABSTRACT FROM AUTHOR]

Background: Trimethylamine-N-Oxide (TMAO) is believed to be linked to increased likelihood of cardiovascular disease. While probiotics have shown limited effectiveness in reducing TMAO levels, the potential of postbiotics remains underexplored. This study aimed to evaluate the impact of Akkermansia muciniphila (A. muciniphila) postbiotic administration on choline-induced TMAO production in mice by modifying the gut microbiota. Methods: Female C57BL/6J mice were divided into six groups, including a control group, high-choline diet group, live A. muciniphila probiotic group, pasteurized A. muciniphila postbiotic group, sodium butyrate group, and sodium propionate group. Various measurements and analyses were conducted, including TMAO and TMA levels in serum, urine, and cecal contents, as well as the expression of FXR and FMO3 in liver tissues. Additionally, metabolic parameters, body weight, serum lipid profile, hepatic protein expression (FMO3, FXR, CutC, and CutD), and gut microbiota composition were assessed. Results: Administration of A. muciniphila postbiotic significantly reduced choline-induced plasma TMAO levels in mice. Furthermore, improvements in serum lipid profiles and liver enzyme levels suggested potential enhancements in lipid metabolism and liver function. The study also observed modulation of specific proteins related to TMAO production and metabolism, including CutC and CutD. Conclusion: The findings highlight the potential of A. muciniphila postbiotics as a dietary strategy for mitigating cardiovascular disease risk by modulating the gut-TMAO axis. Postbiotics, particularly A. muciniphila, offer advantages over probiotics and warrant further investigation for their therapeutic applications in gastrointestinal and metabolic disorders. [ABSTRACT FROM AUTHOR]

Background: Individuals with obesity often experience elevated blood lipid levels, leading to a chronic low-grade inflammatory state, exacerbating liver oxidative stress, and increasing the risk of various metabolic diseases. Recent evidence suggests that intestinal microbiota and short-chain fatty acids (SCFAs) play crucial roles in the development and progression of obesity. While the mechanisms by which Lingguizhugan decoction (LGZGD) intervenes in obesity by improving lipid metabolism, enhancing insulin sensitivity, and reducing inflammatory responses are well-documented, its potential in intestinal microbiota and SCFAs remains unclear. This study aims to explore the impact of LGZGD on high-fat diet (HFD) induced obesity in rats and its regulatory effects on intestinal microbiota and SCFAs, providing new insights for obesity prevention and treatment. Methods: Fifty-one male SD rats were randomly divided into groups, with six in the normal control group (NC) receiving a ddH2O treatment and a standard diet. The remaining 45 rats were fed a high-fat diet (HFD) using D12451 feed. After 10 weeks, the rats on the HFD gained 20% more weight than the NC group, confirming the successful modeling of obesity. These rats were then randomly divided into the following groups: ddH2O high-fat diet model group (MC), 20 mg/kg/day Orlistat positive control group (Orlistat), 1.62 g/kg/day low-dose LGZGD group (LGZGL), and 3.24 g/kg/day high-dose LGZGD group (LGZGH) for 8 weeks. We evaluated changes in body weight, serum total cholesterol (TC), total triacylglycerol (TG), low-density lipoprotein cholesterol (LDL), and high-density lipoprotein cholesterol (HDL) levels. Fat and liver tissues were collected for pathological analysis. Intestinal contents were aseptically collected for 16S rRNA gene sequencing and gas chromatography–mass spectrometry (GC–MS) to assess gut microbiota and SCFA levels. Results: LGZGD reduces body weight, TC, TG, LDL, and HDL levels, significantly reducing hepatic steatosis. Besides, it restored the richness and diversity of gut microbiota, which was reduced by HFD, altering the overall structure. Specifically, LGZGD significantly promoted the growth of Muribaculaceae and Dubosiella while inhibiting the growth of Christensenellaceae_R_7_group and UCG_005. It also restricts the production of caproic acid. Correlation analysis indicated positive correlations: Muribaculaceae with Butyric acid and Isovaleric acid; UCG_005 with TC, LDL, and HDL; and Christensenellaceae_R_7_group with TC and LDL. Conclusion: LGZGD increased the abundance of beneficial gut microbiota in HFD-induced obese rats, improved gut microbiota dysbiosis, and inhibited the increase in caproic acid content. These results suggest that LGZGD can mitigate HFD-induced obesity, and its active components warrant further investigation. [ABSTRACT FROM AUTHOR]

Background: Disturbances in the gut microbiota may act as mechanisms influencing the interplay between dietary factors and metabolic disorders. Studies have demonstrated that these alterations are associated with the diagnosis of polycystic ovary syndrome (PCOS). Within this context, we aimed to investigate associations between gut microbiota, gut-derived metabolites (short-chain fatty acids [SCFAs] and indole-3-propionic acid [IPA]), and dietary intake in women with PCOS. Methods: We conducted a cross-sectional study of 24 women with PCOS, previously recruited for two studies at our research center, compared with 14 age-matched healthy controls. The mean (SD) age of all 38 participants was 33.3 (7.5) years, and the mean (SD) body mass index was 29.5 (4.8) kg/m2. Primary outcomes included gut microbiota analysis by sequencing the V4 region of the 16 S rRNA gene, serum IPA levels measured by liquid chromatography/triple-quadrupole mass spectrometry (LC-QqQ-MS), and fecal and plasma SCFA levels measured by LC-MS/MS. Results: Gut microbiota diversity, composition, and metabolic pathways differed between the PCOS and control groups. A higher abundance of two operational taxonomic units specializing in complex carbohydrate metabolism was observed in healthy control women. The PCOS group exhibited a less favorable dietary intake than the control group, and a significant correlation was observed between gut microbiota composition and dietary glycemic load in PCOS (r = 0.314, P = 0.03 in Mantel test). Multivariable-adjusted linear regression models indicated that lower levels of IPA and higher circulating levels of two SCFAs (acetic acid and propionic acid) were independently associated with the diagnosis of PCOS. Conclusions: Our data support the differentiation between women with PCOS and healthy controls based on gut microbiota analysis. Furthermore, changes in gut bacteria and their metabolites could be, at least in part, the biological mechanism by which a low glycemic load diet may potentially improve PCOS-related reproductive and cardiometabolic outcomes. [ABSTRACT FROM AUTHOR]

Background: The association between alterations in the oral microbiome and hand, foot, and mouth disease (HFMD) has been observed in previous studies. Our study, therefore, aimed to identify the structural changes in the oral microbiota and biomarkers in children with HFMD caused by enterovirus A 71 (EV-A71). Methods: Children diagnosed with EV-A71 HFMD and healthy children recruited from April 2021 to September 2023 were included in the present study, and were categorized into EV-A71 and control groups, respectively. Oral swabs were collected and microbiota information was obtained using 16 S rRNA gene sequencing technology. Alpha-diversity and partial least squares discriminant analyses were conducted to compare microbial diversity, richness, and similarity between the two groups. Linear discriminant analysis effect size was employed to identify microbial taxa with significant differences, and determined the key genera among them. Results: The study included a total of 80 children, with 50 assigned to the EV-A71 group and 30 to the control group. No significant differences were found between the two groups in terms of age (2.2 ± 1.2 vs. 2.7 ± 1.2 years; age range: 1–5 years; P = 0.114) or sex (56% vs. 60% boys, P = 0.726). The oral microbiota structure in the EV-A71 group differed from that in the control group. The EV-A71 group showed significant reductions in both the Shannon index (P = 0.037) and the abundance-based coverage estimator (ACE) index (P < 0.001). The key genus changes were marked by a significant decrease in the abundance of Capnocytophaga (P = 0.002) and Leptotrichia (P = 0.033) in the EV-A71 group. Conclusion: In children with EV-A71 HFMD, the oral microbiota showed changes in composition, with a significant reduction in diversity and richness. The changes in key genera were a marked decrease in the abundance of Capnocytophaga and Leptotrichia. [ABSTRACT FROM AUTHOR]

Background: Research has demonstrated that obesity may be associated with rheumatoid arthritis (RA). In addition, Dysbiosis of intestinal microbiota and their metabolites has been linked to the occurrence and development of RA and obesity. However, the mechanism by which obesity affects RA remains unclear.In this study, we explored the impact of high fat diet(HFD) on collagen-induced arthritis (CIA) rats and revealed its mechanisms based on gut microbiota and metabolomics. Methods: Based on diet and modeling, rats were divided into normal group (Con), CIA model group, HFD group (HFD), and HFD + CIA group (HCIA). The effect of HFD on arthritis in CIA rats were investigated based on the arthritis index (AI), weight, blood lipid levels, and inflammatory cytokines. Moreover, HE staining and micro-CT were performed to evaluated the effect of HFD on the pathology of joints and synovial tissues in CIA rats.16S rRNA amplicon sequencing and liquid chromatography-mass spectrometry (LC–MS) were employed to explore changes in gut microbiota and short-chain fatty acids (SCFAs). Results: The AI scores, inflammatory cytokines and bone destruction parameters in the HCIA group were significantly higher than those in the other three groups. The results of 16S rRNA amplicon sequencing and metabolomics showed that compared with the other three groups, the expression of g_Muribaculaceae and butyric acid were reduced in the HCIA group. Spearman and linear correlation analyses revealed a positive correlation between g_Muribaculaceae abundance and butyric acid levels. Conclusions: HFD stimulated butyric acid metabolism dysbiosis, altered microbiota, and aggravated inflammatory response in CIA rats. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) and schizophrenia (SCH) are common and severe mental disorders that are mainly diagnosed depending on the subjective identification by psychiatrists. Finding potential objective biomarkers that can distinguish these two diseases is still meaningful. Methods: In the present study, we investigate the differences in plasma inflammatory cytokines and short-chain fatty acids (SCFAs) among patients with MDD (n = 24) and SCH (n = 24), and gender- and age-matched healthy controls (HC, n = 27) and identify potential plasma biomarkers. Results: We found that the concentrations of pro-inflammatory cytokines were increased, whereas the anti-inflammatory cytokines were decreased in both MDD and SCH. Meanwhile, except for an increase in 4-Methylvaleric acid, other SCFAs with statistical differences were reduced in both MDD and SCH. Moreover, potential biomarker panels were developed that can effectively discriminate MDD from HC (AUC = 0.997), SCH from HC (AUC = 0.999), and from each other (MDD from SCH, AUC = 0.983). Conclusions: These data suggest that alterations in plasma cytokines and SCFAs might be one of the potential features for distinguishing MDD and SCH. Trial registration: Chinese Clinical Trial Registry: ChiCTR2100051243, registration date: 2021/09/16. [ABSTRACT FROM AUTHOR]

Phenolic compounds show promise in treating obesity and enhancing intestinal health. This systematic review addressed the following question: "What are the effects of polyphenols on intestinal health in preclinical studies with diet-induced obesity?". The review followed PRISMA guidelines and was registered in PROSPERO(CRD42021262445). Studies published until April 2024 were selected from Medline(PubMed), Web of Science, Scopus, Embase, and ScienceDirect using terms related to polyphenols, obesity, and microbiota in rats and mice. Thirty papers meeting PICOS criteria were included. Bias risk was assessed with the SYRCLE tool, yielding scores between 4.5 and 7.0 out of 10. Findings indicated that 22 phenolic compounds improved gut microbiota diversity, reduced the Firmicutes/Bacteroides ratio, and modulated microbiota at various taxonomic levels. They also increased short-chain fatty acids, tight-junction expression, enhanced intestinal morphology, and reduced endotoxemia and inflammatory cytokines. These results suggest phenolic compounds may help treat obesity by modifying the microbiota and improving intestinal health. However, further research is needed to standardize data and facilitate meta-analyses. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to gain deeper insights into the hepatotoxicity mechanisms of valproic acid (VPA), as well as to identify potential risk markers for VPA-induced hepatotoxicity. Methods: Twenty-two children with epilepsy treated with VPA monotherapy were divided into a normal liver function (NLF) group, a mild abnormal liver function (ANLF1) group, and a serious abnormal liver function (ANLF2) group based on their liver function indicator levels. The full quantitative targeted metabolomics technique was used to systematically investigate how the differential endogenous metabolic components change with the development of liver injury. Results: A total of 195 metabolic components were quantitatively analyzed. Nineteen identified metabolites, including five organic acids, four short-chain fatty acids, four amino acids, three fatty acids, and three benzenoids, differed significantly among the three groups, showing a strong association with VPA-induced hepatotoxicity. Only three bile acid metabolites, taurodeoxycholic acid, taurochenodeoxycholic acid, and deoxycholic acid, were significantly different between the ANLF1 and ANLF2 groups, increasing at first and then decreasing with the aggravation of liver injury. The mechanistic evaluation showed that SRT1720 activation could alleviate the severity of liver function abnormalities induced by VPA. Immunocoprecipitation indicated that VPA significantly increased the acetylation level of FXR, and the application of agonist SRT1720 can antagonize the acetylation of FXR by VPA. Conclusion: Nineteen identified metabolites showed a strong association with hepatotoxicity and three bile acid metabolites changed with the development of liver injury. The SIRT1–FXR pathway was firstly proposed to participate in VPA-induced hepatotoxicity. [ABSTRACT FROM AUTHOR]

The present study was designed to investigate the effects of supplementation with freeze-dried Clostridium butyricum (CB) powder on the growth, immune function and intestinal health of Litopenaeus vannamei after replacing fishmeal in the diet with cottonseed protein concentrate (CPC). Six treatment groups were designed, namely the control group (CON, 25% fish meal) and five alternative groups (CPC replacing 40% fishmeal protein in the control group). Based on the alternative group, 0%, 0.065%, 0.26%, 1.04%, and 4.16% of freeze-dried CB bacterial powder (4.6 × 108 CFU/g) were added, recorded as CB 0, CB 0.065, CB 0.26, CB 1.04, and CB 4.16, respectively. Each treatment had 3 replicates of 40 shrimps (0.29 ± 0.01 g) each and breeding for 8 weeks. After the experiment, serum enzyme activities, muscle amino acids, and intestinal parameters (short-chain fatty acids, digestive enzymes, gene expression, and microbiota) were tested to explore the effects of freeze-dried CB powder in shrimp aquaculture. The results showed that the CB1.04 group had the highest final body weight, weight gain rate, and specific growth ratio (P > 0.05). Freeze-dried CB powder increased the activity of serum superoxide dismutase, glutathione peroxidase, complement 3, and complement 4. Muscle tyrosine, proline, and total essential amino acids were remarkably increased in the CB 1.04 group (P < 0.05). Propionic acid levels were elevated in the CB 1.04 and CB4.16 groups (P < 0.001). The relative expression of Dorsal, Relish, and Target of Rapamycin (TOR) genes was significantly increased in the CB 1.04 group (P < 0.01). Actinobacteria and Demequina abundance was significantly higher in the CB 1.04 group (P < 0.01). The results of the Vibrio parahaemolyticus challenge test showed the highest cumulative mortality rate (43.33%) in the CB0 group and the lowest cumulative mortality rate (20%) in the CB1.04 group. This study confirmed that freeze-dried CB powder alleviated the negative effects of CPC replacement of fish meal protein in Litopenaeus vannamei, and the optimum additive level was 2.11% (9.71 × 109 CFU/kg) as indicated by binary regression analysis of specific growth ratio. [ABSTRACT FROM AUTHOR]

BACKGROUND: Studies have shown that short-chain fatty acids (SCFAs) are a potential regulator of skeletal muscle energy metabolism, but the exact mechanism is unclear. OBJECTIVE: To observe the effect of SCFAs on aged rats with sarcopenia and to explore the underlying mechanism. METHODS: Sprague-Dawley rats were randomly divided into control group, sarcopenia group, and sarcopenia + SCFAs group (SCFAs group). In the latter two groups, rat models of sarcopenia were established using ovariectomized rats injected with 5 mg/kg dexamethasone for 7 days. In the control group, the abdominal cavity was only exposed but not removed, and then sutured. Rats in the SCFAs group were administered drinking water containing 150 mmol/L short-chain fatty acids, 600 mg/kg sodium acetate, 200 mg/kg sodium propionate, and 200 mg/kg sodium butyrate for 4 weeks. Rats in the control and sarcopenia groups were given the same volume of normal saline. Successful modeling was assessed by measuring the bilateral gastrocnemius muscle mass and body mass to calculate the gastrocnemius index after modeling. Food intake, body mass and grip strength of rats were measured at 0, 1, 2 and 4 weeks after successful modeling; morphological changes of gastrocnemius muscle were observed by hematoxylin-eosin staining; and the expression of p-AMPK and p-ULK1 proteins in gastrocnemius muscle was detected by western blot. RESULTS AND CONCLUSION: Compared with the control group, the sarcopenia group showed significantly decreased body mass, food intake, forelimb grip strength (P < 0.05), wet mass of gastrocnemius muscle (P < 0.05), and protein levels of p-AMPK and p-ULK1 (P < 0.05). Compared with the sarcopenia group, the SCFAs group showed a significant increase in food intake, body mass, grip strength, wet mass of gastrocnemius muscle, and protein levels of p-AMPK and p-ULK1 in gastrocnemius muscle (P < 0.05). All these findings indicate that SCFAs improve symptoms of sarcopenia in the elderly and may be associated with the upregulation of AMPK and ULK1 proteins in skeletal muscle. [ABSTRACT FROM AUTHOR]

Background: Gut microbiome dysbiosis and related immune dysfunction have been associated with the pathogenesis of Human Cytomegalovirus (HCMV) infection in infants with neonatal cholestasis (NC) as previously reported by us. However, the interaction of a perturbed microbiome, HCMV infection, and dysregulated immunity leading to exacerbation of disease severity has not been investigated so far. In this study, we examined the association of gut microbiome, host inflammatory and homeostatic markers that are likely to govern increased pathogenesis of NC in HCMV infected IgM positive infants (N = 15) compared to IgM negative (N = 15) individuals. Stool samples of HCMV infected infants and age-matched healthy controls (N = 10) were assessed for gut bacteria-derived metabolites like short-chain fatty acids (SCFAs), Lipopolysaccharide (LPS), cytokines and markers of gut barrier integrity. Data were correlated with previously determined gut microbiome composition and frequency of immune cell subsets. Finally, validation of clinical potential was undertaken by principal component analysis (PCA) of integrated data to delineate the spectrum of clinical pathology. Results: Significantly lower levels of SCFAs and elevated fecal levels of soluble inflammatory mediators were observed in IgM positive HCMV infected infants. Further, increased plasma LPS levels and markers of gut permeability, suggestive of microbial translocation due to a 'leaky gut' were observed in HCMV infected IgM positive group. PCA of integrated data revealed clearly disparate profiles representative of IgM positive, IgM negative, and uninfected healthy states. Conclusion: Our results suggest the utility of an integrated approach involving dysregulated microbiome-immune axis for gaining a better understanding of pathogenesis associated with HCMV infection in NC. [ABSTRACT FROM AUTHOR]

One of the emerging non-digestible oligosaccharide prebiotics is β-mannooligosaccharides (β-MOS). β-MOS are β-mannan derived oligosaccharides, they are selectively fermented by gut microbiota, promoting the growth of beneficial microorganisms (probiotics), whereas the growth of enteric pathogens remains unaffected or gets inhibited in their presence, along with production of metabolites such as short-chain fatty acids. β-MOS also exhibit several other bioactive properties and health-promoting effects. Production of β-MOS using the enzymes such as β-mannanases is the most effective and eco-friendly approach. For the application of β-MOS on a large scale, their production needs to be standardized using low-cost substrates, efficient enzymes and optimization of the production conditions. Moreover, for their application, detailed in-vivo and clinical studies are required. For this, a thorough information of various studies in this regard is needed. The current review provides a comprehensive account of the enzymatic production of β-MOS along with an evaluation of their prebiotic and other bioactive properties. Their characterization, structural-functional relationship and in-vivo studies have also been summarized. Research gaps and future prospects have also been discussed, which will help in conducting further research for the commercialization of β-MOS as prebiotics, functional food ingredients and therapeutic agents. [ABSTRACT FROM AUTHOR]

Glucocorticoids (GCs) are key inducers of osteonecrosis, yet not all patients treated with GCs develop glucocorticoid-associated osteonecrosis (GAON). The factors mediating this relationship are unclear. Studies have shown that gut microbiota and their metabolites influence bone metabolism, but their role in GAON is unclear. This study aimed to explore the connection between GAON and gut microbiota. Through bidirectional Mendelian randomization analysis, we identified 14 gut microbial taxa, including Lachnospiraceae (IVW, P = 0.011), associated with GAON. RNA-seq analysis revealed that GAON differentially expressed genes (DEGs) were enriched for intestinal inflammatory response mechanisms. We then compared patients who developed GAON (17 cases), those who did not (GAnON, 15 cases), and those untreated with GCs (Blank, 15 cases) for gut microbiota composition, short-chain fatty acids (SCFAs), and serum inflammatory factors. Our findings indicated a decrease in Lachnospiraceae abundance (GAON 17.13%, GAnON 12.51%, Blank 24.52%) in GC-treated patients. Serum inflammatory factors (IL-17 A, IL-33, and TNF-α) associated with GAON (59.603 ± 12.147, 89.337 ± 20.714, 42.584 ± 9.185) showed significant differences between Blank (1.446 ± 0.683, 11.534 ± 4.705, 4.682 ± 1.48) and GAnON (25.353 ± 8.181, 32.527 ± 7.352, 12.49 ± 3.217) groups, with a negative correlation between these factors and Lachnospiraceae levels. Butyric acid levels in SCFAs varied among groups (P<0.01) and correlated with Lachnospiraceae and inflammatory factors. Controlled experiments in GAON rats demonstrated butyric acid's osteoprotective role in GAON development (P<0.01). In conclusion, our study suggests that reduced Lachnospiraceae and butyric acid levels, along with increased inflammation due to GCs use, contribute to GAON. Butyric acid may mediate the effects of Lachnospiraceae and inflammation. Butyrate supplementation could potentially reduce GAON incidence, offering a novel approach for its clinical management. [ABSTRACT FROM AUTHOR]

Oxidative stress is closely linked to aging. Probiotics, whether viable or heat-inactivated, have shown antioxidant properties; however, their effect and mechanism of action in reducing oxidative stress during aging remains underexplored. This study examined the effects of viable and heat-inactivated Lactiplantibacillus plantarum TY-Y10 (L. plantarum TY-Y10) on D-galactose (D-gal)-induced aging in mice, aiming to uncover potential anti-aging mechanisms. Mice were induced to age with D-gal injections, then treated with sodium ascorbate (positive control) or varying doses of L. plantarum TY-Y10 for eight weeks. After treatment, oxidative stress markers, gut microbiota, and liver health were analyzed. Results showed that L. plantarum TY-Y10 decreased malondialdehyde (MDA) and inflammatory markers while increasing antioxidant levels (glutathione, superoxide dismutase, catalase and glutathione peroxidase). Liver damage was reduced, and expression of Nrf2 and related antioxidant enzymes improved. Additionally, L. plantarum TY-Y10 enhanced the abundance of short-chain fatty acid-producing bacteria, boosting fecal short-chain fatty acid levels. In short, both viable and heat-inactivated L. plantarum TY-Y10 mitigated oxidative stress in aging mice by modulating gut microbiota and activating liver antioxidant pathways through the gut-liver axis. [ABSTRACT FROM AUTHOR]

Background: Numerous studies have established that probiotics or prebiotics can relieve the symptoms of allergic rhinitis (AR), but their mechanism of action remain underexplored. This study aimed to observe the clinical efficacy of probiotics combined with prebiotics in seasonal AR patients and explore their underlying mechanisms. Methods: We conducted a prospective, randomized, double-blind, placebo-controlled clinical trial. The test group was given probiotics combined with prebiotics, whereas the placebo group was administered simulated preparation for 90 days. Outcome measures included total nasal symptom score (TNSS), visual analog scale, rhinitis quality of life questionnaire, fractional exhaled nitric oxide, and the rate and intensity of Loratadine use. Serum TNF-α, INF-γ, IL-4, IL-17, and IgE levels were measured by enzyme-linked immunosorbent assay. Intestinal microbiota was detected by 16S rRNA gene sequencing and quantitative PCR. Short-chain fatty acids were analyzed by gas chromatography-mass spectrometry. Results: 106 participants (N = 53 for both test group and placebo group) completed the study. From baseline to day 91, mean difference between groups (MDBG) in the reduction of TNSS was -1.1 (-2.2, -0.1) (P = 0.04); MDBG in the increment of TNF-α was 7.1 pg/ml (95% CI: 0.8, 13.4, P = 0.03); the INF-γ level was significantly increased (P = 0.01), whereas that of IL-17 (P = 0.005) was significantly decreased in the test group, whilst mean difference within groups was not statistically significant in the placebo group; MDBG in the increment of acetate was 12.4% (95% CI: 7.1%, 17.6%, P <0.001). After the administration of probiotics and prebiotics, the composition and metabolic function of the intestinal microbiota were significantly altered and positively related to the beneficial effect on seasonal AR patients. Conclusion: Probiotics combined with prebiotics administered for 90 days significantly attenuated the symptoms of seasonal AR patients, which may related to fluctuations in the composition and metabolic function of the intestinal microbiota and further ameliorating host immunity. [ABSTRACT FROM AUTHOR]

Background: Despite the growing number of studies investigating the connection between host genetics and the rumen microbiota, there remains a dearth of systematic research exploring the composition, function, and metabolic traits of highly heritable rumen microbiota influenced by host genetics. Furthermore, the impact of these highly heritable subsets on lactation performance in cows remains unknown. To address this gap, we collected and analyzed whole-genome resequencing data, rumen metagenomes, rumen metabolomes and short-chain fatty acids (SCFAs) content, and lactation performance phenotypes from a cohort of 304 dairy cows. Results: The results indicated that the proportions of highly heritable subsets (h2 ≥ 0.2) of the rumen microbial composition (55%), function (39% KEGG and 28% CAZy), and metabolites (18%) decreased sequentially. Moreover, the highly heritable microbes can increase energy-corrected milk (ECM) production by reducing the rumen acetate/propionate ratio, according to the structural equation model (SEM) analysis (CFI = 0.898). Furthermore, the highly heritable enzymes involved in the SCFA synthesis metabolic pathway can promote the synthesis of propionate and inhibit the acetate synthesis. Next, the same significant SNP variants were used to integrate information from genome-wide association studies (GWASs), microbiome-GWASs, metabolome-GWASs, and microbiome-wide association studies (mWASs). The identified single nucleotide polymorphisms (SNPs) of rs43470227 and rs43472732 on SLC30A9 (Zn2+ transport) (P < 0.05/nSNPs) can affect the abundance of rumen microbes such as Prevotella_sp., Prevotella_sp._E15-22, Prevotella_sp._E13-27, which have the oligosaccharide-degradation enzymes genes, including the GH10, GH13, GH43, GH95, and GH115 families. The identified SNPs of chr25:11,177 on 5s_rRNA (small ribosomal RNA) (P < 0.05/nSNPs) were linked to ECM, the abundance alteration of Pseudobutyrivibrio_sp. (a genus that was also showed to be linked to the ECM production via the mWASs analysis), GH24 (lysozyme), and 9,10,13-TriHOME (linoleic acid metabolism). Moreover, ECM, and the abundances of Pseudobutyrivibrio sp., GH24, and 9,10,13-TRIHOME were significantly greater in the GG genotype than in the AG genotype at chr25:11,177 (P < 0.05). By further the SEM analysis, GH24 was positively correlated with Pseudobutyrivibrio sp., which was positively correlated with 9,10,13-triHOME and subsequently positively correlated with ECM (CFI = 0.942). Conclusion: Our comprehensive study revealed the distinct heritability patterns of rumen microbial composition, function, and metabolism. Additionally, we shed light on the influence of host SNP variants on the rumen microbes with carbohydrate metabolism and their subsequent effects on lactation performance. Collectively, these findings offer compelling evidence for the host-microbe interactions, wherein cows actively modulate their rumen microbiota through SNP variants to regulate their own lactation performance. C1VA69ck9huqCRa2wNrTKW Video Abstract [ABSTRACT FROM AUTHOR]

Recent research suggests that microbial molecules translocated from the intestinal lumen into the host's internal environment may play a role in various physiological functions, including sleep. Previously, we identified that butyrate, a short-chain fatty acid produced by intestinal bacteria, and lipoteichoic acid, a cell wall component of gram-positive bacteria, induce sleep when their naturally occurring translocation is mimicked by direct delivery into the portal vein. Building upon these findings, we aimed to explore the sleep signaling potential of intraportally administered lipopolysaccharide (LPS), a primary component of gram-negative bacterial cell walls, in rats. Low dose of LPS (1 μg/kg) increased sleep duration and prolonged fever, without affecting systemic LPS levels. Interestingly, administering LPS systemically outside the portal region at a dose 20 times higher did not affect sleep, indicating a localized sensitivity within the hepatoportal region for the sleep and febrile effects of LPS. Furthermore, both the sleep- and fever-inducing effects of LPS were inhibited by indomethacin, a prostaglandin synthesis inhibitor, and replicated by intraportal administration of prostaglandin E2 or arachidonic acid, suggesting the involvement of the prostaglandin system in mediating these actions. [ABSTRACT FROM AUTHOR]

The gut microbiome primarily generates short-chain fatty acids (SCFAs) by fermenting dietary fibers. Though previous studies have linked SCFAs to blood pressure, there remains a lack of research on the relationship between SCFAs levels in the serum of elderly individuals and blood pressure. Based on this, we investigated the associations of serum SCFAs with blood pressure in Chinese older adults in a cross-sectional study. In this report, we recruited 1013 older adults over 60 years of age from June to September 2016 in Lu 'an City, China. Using Ultra High Performance Liquid Chromatography-Quadrupole-Exactive-Orbitrap-Mass Spectrometry (UHPLC-QE-Orbitrap MS), we measured the level of various SCFAs, including acetic acid (AA), propanoic acid (PA), butyric acid (BA), isobutyric acid (iso-BA), valeric acid (VA), isovaleric acid (iso-VA), and caproic acid (CA), in serum samples collected from Chinese elderly adults. The study recruited 1013 older adults in total. Multiple logistic regression analysis shows that AA (OR = 0.696, 95%CI: 0.501–0.966) and VA (OR = 0.713, 95%CI: 0.516–0.985) are negatively associated with hypertension. Linear regression analysis shows a negative correlation between AA (β = -3.89, 95% CI: -7.12 – -0.66) and the systolic blood pressure (SBP) levels, and a significant negative association between iso-VA (β = -2.11, 95% CI: -3.94 – -0.29) and diastolic blood pressure (DBP) levels. Whether in unadjusted or adjusted linear regression models, we all observe significant positive associations between CA and blood pressure levels. In the Bayesian kernel-machine regression (BKMR) models, the trends between the mixture of SCFAs and hypertension, SBP are inverse, but not significant; we also observe a significant negative correlation between AA and SBP, and a significant negative association between iso-VA and DBP levels, while CA is significantly positively correlated with SBP and DBP. Collectively, our results advocate for considering SCFA as a potential intervention to lower blood pressure, and especially AA may be a possible target for research. This may provide new perspectives for understanding the role of SCFAs in hypertension. [ABSTRACT FROM AUTHOR]

Background: Chronic ethanol exposure (CEE) is recognized as an important risk factor for depression, and the gut-brain axis has emerged as a key mechanism underlying chronic ethanol exposure-induced anxiety and depression-like behaviors. Short-chain fatty acids (SCFAs), which are the key metabolites generated by gut microbiota from insoluble dietary fiber, exert protective roles on the central nervous system, including the reduction of neuroinflammation. However, the link between gut microbial disturbances caused by chronic ethanol exposure, production of SCFAs, and anxiety and depression-like behaviors remains unclear. Methods: Initially, a 90-day chronic ethanol exposure model was established, followed by fecal microbiota transplantation model, which was supplemented with SCFAs via gavage. Anxiety and depression-like behaviors were determined by open field test, forced swim test, and elevated plus-maze. Serum and intestinal SCFAs levels were quantified using GC-MS. Changes in related indicators, including the intestinal barrier, intestinal inflammation, neuroinflammation, neurotrophy, and nerve damage, were detected using Western blotting, immunofluorescence, and Nissl staining. Results: Chronic ethanol exposure disrupted with gut microbial homeostasis, reduced the production of SCFAs, and led to anxiety and depression-like behaviors. Recipient mice transplanted with fecal microbiota that had been affected by chronic ethanol exposure exhibited impaired intestinal structure and function, low levels of SCFAs, intestinal inflammation, activation of neuroinflammation, a compromised blood-brain barrier, neurotrophic defects, alterations in the GABA system, anxiety and depression-like behaviors. Notably, the negative effects observed in these recipient mice were significantly alleviated through the supplementation of SCFAs. Conclusion: SCFAs not only mitigate damage to intestinal structure and function but also alleviate various lesions in the central nervous system, such as neuroinflammation, and reduce anxiety and depression-like behaviors, which were triggered by transplantation with fecal microbiota that had been affected by chronic ethanol exposure, adding more support that SCFAs serve as a bridge between the gut and the brain. [ABSTRACT FROM AUTHOR]

Objective: NOTES gallbladder‐preserving surgery (N‐GPS) has been heralded as a new paradigm shift in minimally invasive surgery for chronic cholecystitis patients. The objective of this research was to evaluate the impact of N‐GPS on the intestinal microbiota of patients. Methods: The study selected patients with benign gallbladder disease (BG group) within 1 week preoperative (BG_DPR stage) and followed up over 1 year postoperative (BG_YPO stage) and selected healthy controls (HC group) whose sex, age, and BMI index matched with patients at BG_YPO stage, too. Accordingly, stool samples from healthy controls and two stages of patients with benign gallbladder disease were collected; among them, the selected samples were sent for 16S rDNA sequencing with Illumina MiSeq platform, and then, the combined samples were sent for short‐chain fatty acid (SCFA) analysis with GC‐MS platform. Results: The result of alpha diversity of Shannon index showed that the difference among the two stages of BG group and HC group wasn't statistically significant, while the result of beta diversity based on the weighted UniFrac distance suggested that the structure of intestinal microbiota of BG group at YPO stage was closer to HC group. LEfSe analysis suggested that BG_YPO stage enriched genus, such as Enterocloster and Hungatella_A_128155, which improved bile acid metabolism. Compared with BG_DPR stage, BG_YPO stage and HC group enriched Faecalibacterium and Roseburia, but depleted Streptococcus, while fecal SCFA concentrations increased. Conclusion: Patients with benign gallbladder disease and chronic cholecystitis after N‐GPS treatment for over 1 year improved gut microbial community structure. With the improving bile acid metabolism, SCFA‐producing bacteria increased and pathobionts decreased, which helped the intestinal microbiota structure of BG group at YPO stage restore and close to HC group. Trial Registration: Chinese Clinical Trial Registry identifier: ChiCTR1900028267. [ABSTRACT FROM AUTHOR]

Practical Application Hyperlipidemia is a metabolic disorder resulted from unhealthy dietary and lifestyle habits. Its pathogenesis is possibly linked to gut microbiota dysbiosis. This study investigates the preventive effects of chitosan self‐assembled coconut residue dietary fiber (CRFSC) on hyperlipidemia induced by a high‐fat diet (HFD) and gut microbiota. CRFSC resulted in a significant weight loss of 7.9% in HFD rats and had a preventive effect on all four lipid parameter abnormalities. HFD supplemented with oat group resulted in a weight loss of 3.8% in HFD rats and had no preventive effect on low‐density lipoprotein cholesterol (LDL‐C) abnormalities. Prevention was achieved not only through the modulation of gut microbiota composition and the increase of short‐chain fatty acids (SCFAs) levels, but also through the activation of superoxide dismutase enzyme and the inhibition of malondialdehyde accumulation, all of which are the factors leading to the controlling of lipid abnormalities and oxidative damage. The prevention of lipid parameters by chitosan self‐assembled coconut residue dietary fiber (CRFSC) may be attributed to its richness in chitosan and insoluble dietary fiber, as well as its ability to enrich beneficial bacteria such as Akkermansia, Roseburia, and Ruminococcus. Correlation analysis demonstrated that key bacterial species producing SCFAs, which are rich in the CRFSC diet, had a positive impact on controlling hyperlipidemia. Hence, consumption of a CRFSC diet could serve as an effective strategy for preventing and controlling the development of hyperlipidemia due to its potential ability to regulate gut microbiota and SCFAs.This study showed that dietary fiber from coconut residue after chitosan self‐assembly had preventive effects on overweight, dyslipidemia, and oxidative damage in rats. In addition, CRFSC also increased the content of short‐chain fatty acids in the gut. And improve gut health by affecting gut microbiota. This finding suggests that CRFSC can be used as a dietary strategy to prevent hyperlipidemia and has practical significance in developing new healthy foods. [ABSTRACT FROM AUTHOR]

The incidence of insulin resistance (IR) and hepatic steatosis is increasing, with dietary fiber playing a protective role against these disorders. Ocimum basilicum L., widely used in food, pharmaceutical, and cosmetic industries, but their health-promoting properties remain underexplored. This study evaluated the effects of a fiber-rich fraction of partially defatted basil seeds (BSF) on IR, hepatic steatosis, and polyunsaturated fatty acid and short-chain fatty acid (SCFA) profiles in high-fat diet (HFD)-fed C57BL/6 J male mice. Mice were assigned to four groups and fed either a control diet or HFD, supplemented with BSF or oat flour for 4 weeks. HFD induced IR, hepatic steatosis, proinflammatory state, and a significant decreased in SCFA production. In contrast, supplementation with BSF attenuated IR, steatosis, liver damage, oxidative stress, and inflammation, while increasing n-3 polyunsaturated fatty acids in liver, adipocytes, and erythrocytes, and enhancing SCFA production, suggesting potential therapeutic benefits in managing these conditions. [ABSTRACT FROM AUTHOR]

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the most efficient therapeutic options available to cure many hematological malignancies. However, severe complications derived from this procedure, including graft-versus-host disease (GVHD) and infections, can limit its success and negatively impact survival. Previous studies have shown that alterations in the microbiome are associated with the development of allo-HSCT-derived complications. However, most studies relied on single techniques that can only analyze a unique aspect of the microbiome, which hinders our ability to understand how microbiome alterations drive allo-HSCT-associated diseases. Results: Here, we have applied multiple "omic" techniques (16S rRNA and shotgun sequencing, targeted and un-targeted metabolomics) in combination with machine learning approaches to define the most significant microbiome changes following allo-HSCT at multiple modalities (bacterial taxa, encoded functions, and derived metabolites). In addition, multivariate approaches were applied to study interactions among the various microbiome modalities (the interactome). Our results show that the microbiome of transplanted patients exhibits substantial changes in all studied modalities. These include depletion of beneficial microbes, mainly from the Clostridiales order, loss of their bacterial encoded functions required for the synthesis of key metabolites, and a reduction in metabolic end products such as short chain fatty acids (SCFAs). These changes were followed by an expansion of bacteria that frequently cause infections after allo-HSCT, including several Staphylococcus species, which benefit from the reduction of bacteriostatic SCFAs. Additionally, we found specific alterations in all microbiome modalities that distinguished those patients who subsequently developed GVHD, including depletion of anti-inflammatory commensals, protective reactive oxygen detoxifying enzymes, and immunoregulatory metabolites such as acetate or malonate. Moreover, extensive shifts in the homeostatic relationship between bacteria and their metabolic products (e.g., Faecalibacterium and butyrate) were detected mainly in patients who later developed GVHD. Conclusions: We have identified specific microbiome changes at different modalities (microbial taxa, their encoded genes, and synthetized metabolites) and at the interface between them (the interactome) that precede the development of complications associated with allo-HSCT. These identified microbial features provide novel targets for the design of microbiome-based strategies to prevent diseases associated with stem cell transplantation. Bx_7phuTozz8yFUTR9cZV4 Video Abstract [ABSTRACT FROM AUTHOR]

This paper reviews the effects of gut microbiota in regulating neurodegenerative diseases through controlling gut-brain axis. Specific microbial populations and their metabolites (short-chain fatty acids and tryptophan derivatives) regulate neuroinflammation, neurogenesis and neural barrier integrity. We then discuss ways by which these insights lead to possible interventions - probiotics, prebiotics, dietary modification, and fecal microbiota transplantation (FMT). We also describe what epidemiological and clinical studies have related certain microbiota profiles with the courses of neurodegenerative diseases and how these impact the establishment of microbiome-based diagnostics and individualized treatment options. We aim to guide microbial ecology research on this key link to neurodegenerative disorders and also to highlight collaborative approaches to manage neurological health by targeting microbiome-related factors. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD) is a refractory inflammatory disorder of the intestine, which is probably triggered by dysfunction of the intestinal epithelial barrier. Secretory leukocyte protease inhibitor (SLPI) secreted by colon epithelial cells protects against intestinal inflammation by exerting anti-protease and anti-microbial activities. Daikenchuto (DKT) is one of the most commonly prescribed Japanese traditional herbal medicines for various digestive diseases. Although several animal studies have revealed that DKT exerts anti-inflammatory effects, its detailed molecular mechanism is unclear. This study aimed to clarify the anti-inflammatory mechanism of DKT using a murine colitis model, and to evaluate its potential as a therapeutic agent for IBD. Methods: Experimental colitis was induced in wild-type (WT) mice and SLPI-deficient (KO) mice by dextran sulfate sodium (DSS) after oral administration of DKT. The resultant clinical symptoms, histological changes, and pro-inflammatory cytokine levels in the colon were assessed. Expression of SLPI in the colon was detected by Western blotting and immunohistochemistry. Composition of the gut microbiota was analyzed by 16S rRNA metagenome sequencing and intestinal metabolites were measured by gas chromatography-mass spectrometry analysis. Intestinal epithelial barrier function was assessed by oral administration of FITC-dextran and immunostaining of tight junction proteins (TJPs). Results: Oral administration of DKT increased the number of butyrate-producing bacteria, such as Parabacteroides , Allobaculum , and Akkermansia , enhanced the levels of short-chain fatty acids, including butyrate, in the colon, induced SLPI expression, and ameliorated DSS-induced colitis in WT mice. We found that mouse colon carcinoma cell line treatment with either DKT or butyrate significantly enhanced the expression of SLPI. Moreover, supplementation of DKT protected the intestinal epithelial barrier with augmented expression of TJPs in WT mice, but not in KO mice. Finally, the composition of the gut microbiota was changed by DKT in WT mice, but not in KO mice, suggesting that DKT alters the colonic bacterial community in an SLPI-dependent manner. Conclusion: These results indicate that DKT exerts anti-inflammatory effects on the intestinal epithelial barrier by SLPI induction, due, at least in part, to increased butyrate-producing bacteria and enhanced butyrate levels in the colon. These results provide insight into the mechanism of the therapeutic effects of DKT on IBD. [ABSTRACT FROM AUTHOR]

The great potential of polysaccharides in immunological regulation has recently been highlighted in pharmacological and clinical studies. Polysaccharides can trigger immunostimulatory responses through molecular identification, intra- and intercellular communication via direct or indirect interactions with the immune system. Various immunostimulatory polysaccharides or their derivative compounds interacts at cellular level to boost the immune system, including arabinogalactans, fucoidans, mannans, xylans, galactans, hyaluronans, fructans, pectin and arabinogalactans, etc. These natural polysaccharides are derived from various plants, animals and microbes. A unique structural diversity has been identified in polysaccharides, while monosaccharides and glucosidic bonds mainly confer diverse biological activities. These natural polysaccharides improve antioxidant capacity, reduce the production of pro-inflammatory mediators, strengthen the intestinal barrier, influence the composition of intestinal microbial populations and promote the synthesis of short-chain fatty acids. These natural polysaccharides are also known to reduce excessive inflammatory responses. It is crucial to develop polysaccharide-based immunomodulators that could be used to prevent or treat certain diseases. This review highlights the structural features, immunomodulatory properties, underlying immunomodulatory mechanisms of naturally occurring polysaccharides, and activities related to immune effects by elucidating a complex relationship between polysaccharides and immunity. In addition, the future of these molecules as potential immunomodulatory components that could transform pharmaceutical applications at clinical level will also be highlighted. [ABSTRACT FROM AUTHOR]

Sleep disorders are becoming more and more common, leading to many health problems. However, most of current available medications to treat sleep disorders are addictive and even impair cognitive abilities. Therefore, it is important to find a natural and safe alternative to treat sleep disorders. In this study, twenty-four 8-week-old male ICR mice (25 ± 2 g) were equally divided into three groups: the control group (gavage of 0.9% saline), the eucalyptus essential oil (EEO) group (10 mg/kg B.W.), and the diazepam group (1 mg/kg B.W.). Firstly, open field test and sleep induction test were used to determine the sedative-hypnotic effect of EEO. Secondly, the effect of EEO on neurotransmitters in the mice brain was determined. Finally, based on the gut microbiota-brain axis (GMBA), the effect of EEO on the intestinal flora of mice was explored. It was found that EEO significantly reduce the activity and prolong the sleep duration of mice, exhibiting a good sedative-hypnotic effect. In the brain, EEO could increase the levels of sleep-promoting neurotransmitters, such as glutamine, Gamma-aminobutyric acid (GABA), glycine, tryptophan, N-acetylserotonin, and 5-hydroxyindoleacetic acid (5-HIAA). In the intestine, EEO was found to increase the diversity of gut microbes, the abundance of short chain fatty acid (SCFA) producing flora, and the abundance of functional flora synthesizing GABA and glycine neurotransmitters. These studies suggested that EEO exerted a sedative-hypnotic effect by acting on gut microbes and neurotransmitters in the brain. EEO has the potential to become a natural and safe alternative to traditional hypnotic sedative drugs. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD) increases the risk of colorectal cancer, and it has the potential to diminish the quality of life. Clinical and experimental evidence demonstrate protective aspects of parasitic helminth infection against IBD. However, studies on the inhibition of inflammation by helminth infection have overlooked a key determinant of health: the gut microbiota. Although infection with helminths induces alterations in the host microbiota composition, the potential influence and mechanism of helminth infections induced changes in the gut microbiota on the development of IBD has not yet been elucidated. In this study, we analyzed the intersection of helminth Trichinella spiralis and gut bacteria in the regulation of colitis and related mechanisms. Methodology/Principal findings: T. spiralis infected mice were treated with antibiotics or cohoused with wild type mice, then challenged with dextran sodium sulfate (DSS)-colitis and disease severity, immune responses and goblet cells assessed. Gut bacteria composition was assessed by 16S rRNA sequencing and short-chain fatty acids (SCFAs) were measured. We found that protection against disease by infection with T. spiralis was abrogated by antibiotic treatment, and cohousing with T. spiralis- infected mice suppressed DSS-colitis in wild type mice. Bacterial community profiling revealed an increase in the abundance of the bacterial genus Muribaculum and unclassified_Muribaculaceae in mice with T. spiralis infection or mice cohoused with T. spiralis- infected mice. Metabolomic analysis demonstrated significantly increased propionic acid in feces from T. spiralis- infected mice. Data also showed that the gut microbiome modulated by T. spiralis exhibited enhanced goblet cell differentiation and elevated IL-10 levels in mice. Conclusions: These findings identify the gut microbiome as a critical component of the anti- colitic effect of T. spiralis and gives beneficial insights into the processes by which helminth alleviates colitis. Author summary: IBD encompasses Crohn's Disease and Ulcerative Colitis. It affects both children and adults. Reports have highlighted the potential use of helminths or their byproducts as a possible treatment for IBD. Accumulating evidence also suggests that the gut microbiota is a key factor in modulating IBD. In this study, we revealed the protective effect of a prior infection with T. spiralis on DSS- induced colitis in mice. Specifically, T. spiralis infection reshaped the gut microbiome of mice, resulting in an increased abundance of SCFA-producing bacteria Muribaculum and unclassified_Muribaculaceae and thereby producing a larger amount of propionic acid. Furthermore, the gut microbiome modulated by T. spiralis exhibited enhanced goblet cell differentiation and elevated IL-10 levels, ultimately ameliorating experimental colitis. These findings suggest that the modulation of host microbiota during T. spiralis infection plays a crucial role in the suppression of colitis, and any intention-to-treat with helminth therapy should be based on the patient's immunological and microbiological response to the helminth. [ABSTRACT FROM AUTHOR]

The gut microbiota may help mitigate bone loss linked to postmenopausal osteoporosis by affecting the immune and inflammatory responses and the gut-bone axis. Dihydromyricetin (DMY), a natural flavonoid, has some anti-inflammatory and antioxidant properties. This study aimed to investigate the mechanisms underlying the amelioration of bone loss in ovariectomized (OVX) mice treated with various doses of DMY. Eight-week-old C57/BL6 mice underwent ovariectomy and received varying DMY doses over 8 weeks. Thereafter, femoral bone microarchitecture, serum biomarker levels, and colon samples were analyzed to assess bone metabolism and inflammatory and hormonal responses. Fecal samples were subjected to 16S rDNA sequencing, and short-chain fatty acids were quantified. An untargeted metabolomics approach was applied to both serum and fecal samples to investigate alterations in the intestinal microbiota and metabolic profiles following DMY treatment in the OVX mice. The results show high-dose DMY has anti-osteoporotic effects. Compared to the OVX group, the DMY-treated group showed enhanced bone mineral density and reduced inflammation and colonic damage levels. The DMY treatment altered the gut microbiota composition, including the relative abundances at both the phylum and genus levels. In addition, DMY treatment increased the production of acetate and propionate. Metabolomic analysis revealed differential regulation of 37 and 70 metabolites in the serum and feces samples, respectively, in the DMY-treated group compared to those in the OVX group, affecting the serotonergic signaling, arachidonic acid metabolism, and unsaturated fatty acid biosynthesis pathways. In conclusion, these findings indicate that DMY can ameliorate bone loss in OVX mice via the gut-bone axis. DMY can ameliorate bone loss in OVX mice via the gut-bone axis. [ABSTRACT FROM AUTHOR]

Cancer remains a multifactorial disease with an increased mortality rate around the world for the past several decades. Despite advancements in treatment strategies, lower survival rates, drug-associated side effects, and drug resistance create a need for novel anticancer agents. Ample evidence shows that imbalances in the gut microbiota are associated with the formation of cancer and its progression. Altering the gut microbiota via probiotics and their metabolites has gained attention among the research community as an alternative therapy to treat cancer. Probiotics exhibit health benefits as well as modulate the immunological and cellular responses in the host. Apart from probiotics, their secreted products like bacteriocins, exopolysaccharides, short-chain fatty acids, conjugated linoleic acid, peptidoglycan, and other metabolites are found to possess anticancer activity. The beneficiary role of these postbiotic compounds is widely studied for characterizing their mechanism and mode of action that reduces cancer growth. The present review mainly focuses on the postbiotic components that are employed against cancer with their reported mechanism of action. It also describes recent research works carried out so far with specific strain and anticancer activity of derived compounds both in vitro and in vivo , validating that the probiotic approach would pave an alternative way to reduce the burden of cancer. [ABSTRACT FROM AUTHOR]

Flagella is a well-known bacterial structure crucial for motility, which also plays pivotal roles in pathogenesis. Arcobacter butzleri, an enteropathogen, possesses a distinctive polar flagellum whose functional aspects remain largely unexplored. Upon investigating the factors influencing A. butzleri motility, we uncovered that environmental conditions like temperature, oxygen levels, and nutrient availability play a significant role. Furthermore, compounds that are found in human gut, such as short-chain fatty acids, mucins and bile salts, have a role in modulating the motility, and in turn, the pathogenicity of A. butzleri. Further investigation demonstrated that A. butzleri ΔflaA mutant showed a reduction in motility with a close to null average velocity, as well as a reduction on biofilm formation. In addition, compared with the wild-type, the ΔflaA mutant showed a decreased ability to invade Caco-2 cells and to adhere to mucins. Taken together, our findings support the role of environmental conditions and gut host associated compounds influencing key physiological aspects of the gastrointestinal pathogen A. butzleri, such as motility, and support the role of the flagellum on bacterial virulence. [ABSTRACT FROM AUTHOR]