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Background Age‐related muscle dysfunctions are common disorders resulting in poor quality of life in the elderly. Probiotic supplementation is a potential strategy for preventing age‐related sarcopenia as evidence suggests that probiotics can enhance muscle function via the gut–muscle axis. However, the effects and mechanisms of probiotics in age‐related sarcopenia are currently unknown. In this study, we examined the effects of Lactobacillus casei Shirota (LcS), a probiotic previously reported to improve muscle function in young adult mice. Methods We administered LcS (1 × 108 or 1 × 109 CFU/mouse/day) by oral gavage to senescence‐accelerated mouse prone‐8 mice for 12 weeks (16‐ to 28‐week‐old). Sixteen‐week‐old and 28‐week‐old SMAP8 mice were included as non‐aged and aged controls, respectively. Muscle condition was evaluated using dual‐energy X‐ray absorptiometry for muscle mass, holding impulse and grip strength tests for muscle strength, and oxygen consumption rate, gene expressions of mitochondrial biogenesis, and mitochondrial number assays for mitochondria function. Inflammatory cytokines were determined using enzyme‐linked immunosorbent assay. Gas chromatography–mass spectrometry was utilized to measure the short‐chain fatty acid levels. The gut microbiota was analysed based on the data of 16S rRNA gene sequencing of mouse stool. Results The LcS supplementation reduced age‐related declines in muscle mass (>94.6%, P 66% in holding impulse and >96.3% in grip strength, P 65.9% in the mice given high dose of LcS, P 89.4%, P 2.0] were positively correlated with healthy muscle and physiological condition (P 2.0) were negatively associated with healthy muscle and physiological condition (P

OBJECTIVE. To test the hypothesis that an altered gut microbiota (dysbiosis) plays a role in obesity-associated osteoarthritis (OA). METHODS. Stool and blood samples were collected from 92 participants with BMI ≥ 30 kg/m(2) recruited from the Johnston County Osteoarthritis Project. OA cases (n=50) had hand plus knee OA (Kellgren-Lawrence [KL] grade ≥2 or arthroplasty). Controls (N=42) had no hand OA and KL grade 0–1 knees. Compositional analysis of stool samples was carried out by 16S rRNA amplicon sequencing. Alpha and beta diversity and differences in taxa relative abundances were determined. Blood samples were used for multiplex cytokine analysis and measures of lipopolysaccharide (LPS) and LPS binding protein. Germ-free mice were gavaged with case or control pooled fecal samples and placed on a 40% fat, high sucrose diet for 40 weeks. Knee OA was evaluated histologically. RESULTS. OA cases were slightly older with more females and higher BMI, WOMAC pain and KL grades than controls. There were no significant differences in alpha or beta diversity or genus level composition between cases and controls. Cases had higher plasma levels of osteopontin (p=0.01) and serum LPS (p

Streptococcus uberis is a common cause of mastitis. The pathogenicity among different strains of S. uberis and the resultant host immune responses remain to be elucidated. Herein, we document immune responses among 3 strains of S. uberis, and preliminary explore whether and how intestinal immunity play a role in host anti-infection processes. Mice have been proved to be effective experimental animals for bovine mastitis, so utilizing a mouse intramammary infection model, we assay immune responses and gut flora changes of 3 S. uberis strains by histopathologic examination, RT-PCR, Western blot and 16s rDNA sequencing. We find that the immune responses among the 3 sequence type (ST) S. uberis strains may be linked to the hasA/B and lbp virulence genes, and the beta diversity of the intestinal may be independent of the ST type of S. uberis. Twenty phyla and 30 genera of intestinal flora are identified, Verrucomicrobia and Akkermansia being the most prominent phylum and genus respectively. These bacteria have strong anti-inflammatory and protective effects against S. uberis challenge. These datas provide a foundation for further studies to elucidate gut flora function and exploration of therapeutic targets for mastitis. This article is protected by copyright. All rights reserved.

Summary Heat acclimation (HA) is the best strategy to improve heat stress tolerance by inducing positive physiological adaptations. Evidence indicates that the gut microbiome plays a fundamental role in the development of HA, and modulation of gut microbiota can improve tolerance to heat exposure and decrease the risks of heat illness. In this study, for the first time, we applied 16S rRNA gene sequencing and untargeted liquid chromatography–mass spectrometry (LC‐MS) metabolomics to explore variations in the gut microbiome and faecal metabolic profiles in rats after HA. The gut microbiota of HA subjects exhibited higher diversity and richer microbes. HA altered the gut microbiota composition with significant increases in the genera Lactobacillus (a major probiotic) and Oscillospira alongside significant decreases in the genera Blautia and Allobaculum. The faecal metabolome was also significantly changed after HA, and among the 13 perturbed metabolites, (S)‐AL 8810 and celastrol were increased. Moreover, the two increased genera were positively correlated with the two upregulated metabolites and negatively correlated with the other 11 downregulated metabolites, while the correlations between the two decreased genera and the upregulated/downregulated metabolites were completely contrary. In summary, both the structure of the gut microbiome community and the faecal metabolome were improved after 28 days of HA. These findings provide novel insights regarding the improvement of the gut microbiome and its functions as a potential mechanism by which HA confers protection against heat stress., Evidence indicates that the gut microbiome plays a fundamental role in the development of HA. In this study, we applied 16S rRNA gene sequencing and untargeted liquid chromatography‐mass spectrometry (LC‐MS) metabolomics to explore variations in the gut microbiome and fecal metabolic profiles in rats after HA. Our study demonstrates for the first time that HA has a significant effect on the gut microbiome and fecal metabolome, and this may be a potential mechanism by which HA confers protection against heat stress.

Summary Intestinal flora provides an important contribution to the development of pulmonary tuberculosis (PTB). We performed a cross‐sectional study in 52 healthy controls (HCs) and 83 patients with untreated active PTB to assess the differences in their microbiomic and metabolic profiles in faeces via V3‐V4 16S rRNA gene sequencing and gas chromatography–mass spectrometry. Patients with PTB had considerable reductions in phylogenetic alpha diversity and the production of short‐chain fatty acids, dysbiosis of the intestinal flora and alterations in the faecal metabolomics composition compared with HCs. Significant alterations in faecal metabolites were associated with changes in the relative abundance of specific genera. Our study describes the imbalance of the gut microbiota and altered faecal metabolomics profiles in patients with PTB; the results indicate that the gut microbiota and faecal metabolomic profiles can be used as potential preventive and therapeutic targets for PTB., The imbalance of the gut microbiota and altered faecal metabolomics profiles in patients with PTB;Mtb infection decreased the production of SCFAs in faeces.

Response to cardiovascular drugs can vary greatly between individuals, and the role of the microbiome in this variability is being increasingly appreciated. Recent evidence indicates that bacteria and other microbes are responsible for direct and indirect effects on drug efficacy and toxicity. Pharmacomicrobiomics aims to uncover variability in drug response due to microbes in the human body, which may alter drug disposition through microbial metabolism, interference by microbial metabolites, or modification of host enzymes. In this review, we present recent advances in our understanding of the interplay between microbes, host metabolism, and cardiovascular drugs. We report numerous cardiovascular drugs with evidence of, or potential for, gut-microbe interactions. However, the effects of gut microbiota on many cardiovascular drugs are yet uninvestigated. Finally, we consider potential clinical applications for the described findings.

Western-style high-fat/high-sucrose diet (HFHSD) changes gut microbiota and bile acid (BA) profiles. Because gut microbiota and BAs could influence each other, the mechanism of changes in both by HFHSD is complicated and remains unclear. We first aimed to clarify the roles of BAs in the HFHSD-induced change of gut microbiota. Then, we studied the effects of the changed gut microbiota on BA composition and liver function. Male wild-type (WT) and human-like Cyp2a12/Cyp2c70 double knockout (DKO) mice derived from C57BL/6J were fed with normal chow or HFHSD for 4 weeks. Gut microbiomes were analyzed by fecal 16S ribosomal RNA gene sequencing, and BA composition was determined by liquid chromatography-tandem mass spectrometry. The DKO mice exhibited significantly reduced fecal BA concentration, lacked muricholic acids, and increased proportions of chenodeoxycholic and lithocholic acids. Despite the marked difference in the fecal BA composition, the profiles of gut microbiota in the two mouse models were quite similar. An HFHSD resulted in a significant increase in the BA pool and fecal BA excretion in WT mice but not in DKO mice. However, microbial composition in the two mouse models was drastically but similarly changed by the HFHSD. In addition, the HFHSD-induced change of gut microbiota inhibited BA deconjugation and 7α-dehydroxylation in both types of mice, which improved chronic liver injury observed in DKO mice. Conclusion: The HFHSD itself causes the change of gut microbiota due to HFHSD, and the altered composition or concentration of BAs by HFHSD is not the primary factor. On the contrary, the gut microbiota formed by HFHSD affects BA composition and ameliorates liver injury in the mouse model with human-like hydrophobic BA composition.

Background Cancer cachexia is a multifactorial metabolic syndrome in which bile acid (BA) metabolism might be involved. The aim of the present study was to clarify the contribution of liver and gut microbiota to BA metabolism disturbance in cancer cachexia and to check the possibility of targeting BA metabolism using agents such as tauroursodeoxycholic acid (TUDCA) for cancer cachexia therapy. Methods The BA profiles in liver, intestine, and serum of mice with cancer cachexia induced by inoculation of colon C26 tumour cells were analysed using metabolomics methods and compared with that of control mice. Proteomic analysis of liver protein expression profile and 16S rRNA gene sequencing analysis of gut microbiota composition in cancer cachexia mice were conducted. Expression levels of genes related to farnesoid X receptor (FXR) signalling pathway in the intestine and liver tissues were analysed using RT–PCR analysis. The BA profiles in serum of clinical colon cancer patients with or without cachexia were also analysed and compared with that of healthy volunteers. The effects of TUDCA in treating cancer cachexia mice were observed. Results In the liver of cancer cachexia mice, expression of BA synthesis enzymes was inhibited while the amount of total BAs increased (P

Background Gut microbiota dysbiosis and sarcopenia commonly occur in the elderly. Although the concept of the gut–muscle axis has been raised, the casual relationship is still unclear. This systematic review analyses the current evidence of gut microbiota effects on muscle/sarcopenia. Methods A systematic review was performed in PubMed, Embase, Web of Science, and The Cochrane Library databases using the keywords (microbiota* OR microbiome*) AND (sarcopen* OR muscle). Studies reporting the alterations of gut microbiota and muscle/physical performance were analysed. Results A total of 26 pre‐clinical and 10 clinical studies were included. For animal studies, three revealed age‐related changes and relationships between gut microbiota and muscle. Three studies focused on muscle characteristics of germ‐free mice. Seventy‐five per cent of eight faecal microbiota transplantation studies showed that the recipient mice successfully replicated the muscle phenotype of donors. There were positive effects on muscle from seven probiotics, two prebiotics, and short‐chain fatty acids (SCFAs). Ten studies investigated on other dietary supplements, antibiotics, exercise, and food withdrawal that affected both muscle and gut microbiota. Twelve studies explored the potential mechanisms of the gut–muscle axis. For clinical studies, 6 studies recruited 676 elderly people (72.8 ± 5.6 years, 57.8% female), while 4 studies focused on 244 young adults (29.7 ± 7.8 years, 55.4% female). The associations of gut microbiota and muscle had been shown in four observational studies. Probiotics, prebiotics, synbiotics, fermented milk, caloric restriction, and exercise in six studies displayed inconsistent effects on muscle mass, function, and gut microbiota. Conclusions Altering the gut microbiota through bacteria depletion, faecal transplantation, and various supplements was shown to directly affect muscle phenotypes. Probiotics, prebiotics, SCFAs, and bacterial products are potential novel therapies to enhance muscle mass and physical performance. Lactobacillus and Bifidobacterium strains restored age‐related muscle loss. Potential mechanisms of microbiome modulating muscle mainly include protein, energy, lipid, and glucose metabolism, inflammation level, neuromuscular junction, and mitochondrial function. The role of the gut microbiota in the development of muscle loss during aging is a crucial area that requires further studies for translation to patients.

Obesity is closely related to dyslipidaemia, diabetes and other metabolic syndromes. Long-term consumption of a high-fat diet (HFD) is an important risk factor that can lead to obesity. In the current research, three Lactobacillus strains, namely, Loigolactobacillus coryniformis subsp. torquens T3 (T3), Lacticasebacillus paracasei subsp. paracasei M5 (M5), and Lacticaseibacillus paracasei subsp. paracasei X12 (X12), were tested to determine their inhibitory effects on HFD-induced obesity. The results showed that M5, T3, and X12 significantly decreased the body weight gain, Lee's index and adipose index. T3 showed significant effects on reducing serum TG levels to 0.92 mmol/ml and increasing HDL-C levels to 2.18 mmol/ml. The M5 treatment significantly reduced the serum TG level and leptin content to 1.11 mmol/ml and 3.7 ng/ml, respectively, and it increased the HDL-C level and adiponectin content to 2.35 mmol/ml and 7 ng/ml, respectively. M5 and T3 dramatically ameliorated hepatic steatosis in HFD-treated mice by reducing the liver index, lipid droplet number in the liver and TC levels in the liver. Gene expression of PPAR-γ and TNF-α was notably downregulated and FAS was upregulated by T3 and M5 treatment. Additionally, administration of M5 and T3 modified the diversity of the gut microbiota with increased OTU number, ACE index, and Chao1, and decreased the Shannon index and the Bacteroidetes /Firmicutes ratio. Overall, our results indicate that Lactobacillus may be used to prevent obesity and gut dysbiosis. PRACTICAL APPLICATION: Lactobacillus from traditional Chinese foods showed strong anti-obesity effects on high-fat diet-fed mice through the regulation of adipocytokines. Additionally, administration of certain Lactobacilli modified the diversity of the gut microbiota. The results indicate that Lactobacillus may be promising functional materials in healthy foods.

Background: High sodium intake is an important risk factor for hypertension and cardiovascular disease. However, the association between gut microbiota composition and metabolomic profiles with dietary sodium intake and blood pressure (BP) is not well-understood. The metabolome, microbiome, and dietary salt intervention (MetaSalt) study aimed to investigate microbial and metabolomic profiles related to dietary sodium intake and BP regulation. Methods: This family-based intervention study was conducted in four communities across three provinces in rural northern China in 2019. Probands with untreated prehypertension or stage-1 hypertension were identified through community-based BP screening, and family members including siblings, offspring, spouses, and parents were subsequently included. All participants participated in a 3-day baseline examination with usual diet consumption, followed by a 10-day low-salt diet (3 g/d of salt or 51.3 mmol/d of sodium) and a 10-day high-salt diet (18 g/d of salt or 307.8 mmol/d of sodium). Differences in mean BP levels were compared according to the intervention phases using a paired Student's t-test. Results: A total of 528 participants were included in this study, with a mean age of 48.1 years, 36.7% of whom were male, 76.8% had a middle school (69.7%) or higher (7.1%) diploma, 23.4% had a history of smoking, and 24.4% were current drinkers. The mean arterial pressure at baseline was 97.2 ± 10.5 mm Hg for all participants, and significantly decreased during the low-salt intervention (93.8 ± 9.3, P

Aim Previous research has shown that individuals with inflammatory bowel disease avoid specific food items, such as fibre rich foods, in order to manage symptoms. Dietary fibre and the traditional Mediterranean diet are both associated with reduced mucosal and systemic inflammation, gut barrier integrity, and microbiota diversity. There is limited data on the diet composition of individuals with inflammatory bowel disease. The aim of this study was to evaluate how it compares to the traditional Mediterranean diet and national dietary guidelines. Methods Outpatients with inflammatory bowel disease were recruited to the study between February and August 2019. Demographic and medical information was obtained for consenting participants. All participants completed a dietary assessment of usual intake (24-h diet recall and 17-point ready reckoner) from which a Mediterranean diet adherence score was calculated. Dietary intake of core food groups was compared to the recommended number of serves outlined in the Australian Guide to Healthy Eating. Results 100 participants were recruited. The mean Mediterranean diet adherence score was 5.1 ± 1.3 (maximum 14 points), 4% of participants scored ≥9 (commonly agreed criteria for Mediterranean diet adherence). Participants also consumed considerably less grains and vegetables than national dietary guidelines recommendations. Conclusions The diet of outpatients with inflammatory bowel disease did not align with Mediterranean diet characteristics. Participants consumed significantly less grains and vegetables than national guidelines, suggesting a low fibre intake. These findings suggest that dietary interventions focusing on improving the diet of individuals with inflammatory bowel disease to align with Mediterranean diet characteristics are warranted.

Background The gut microbiota has been implicated in the pathogenesis of inflammatory bowel disease (IBD), with Faecalibacterium prausnitizii associated with protection, and certain genera (including Shigella and Escherichia) associated with adverse features. The variability of patient response to medical therapies in IBD is incompletely understood. Given the recognised contribution of the microbiota to treatment efficacy in other conditions, there may be interplay between the gut microbiota, IBD medical therapy and IBD phenotype. Aims To evaluate the bidirectional relationship between IBD medical therapies and the gut microbiota. Methods We conducted a systematic search of MEDLINE and EMBASE. All original studies analysing interactions between the gut microbiota and established IBD medical therapies were included. Results We screened 1296 records; 19 studies were eligible. There was heterogeneity in terms of sample analysis, treatment protocols, and outcome reporting. Increased baseline α-diversity was observed in responders versus non-responders treated with exclusive enteral nutrition (EEN), infliximab, ustekinumab or vedolizumab. Higher baseline Faecalibacterium predicted response to infliximab and ustekinumab. A post-treatment increase in Faecalibacterium prausnitzii was noted in responders to aminosalicylates, anti-TNF medications and ustekinumab; conversely, this species decreased in responders to EEN. Escherichia was a consistent marker of unfavourable drug response, and its presence in the gut mucosa correlated with inflammation in aminosalicylate-treated patients. Conclusions Both gut microbiota diversity and specific taxonomic features (including high abundance of Faecalibacterium) are associated with the efficacy of a range of IBD therapies. These findings hold promise for a potential role for the gut microbiota in explaining the heterogeneity of patient response to IBD treatments.

Current studies regarding the effect of different nitrogen sources on gut microbiota have thus far disregarded the ability of probiotics and coliforms to compete for protein. This study aimed to investigate the differences in the utilization of soybean protein (SPro) and its derived peptides (SPep) by the gut microbiota of Sprague Dawley (SD) rats. The SPro and SPep prepared in this study showed extensive SPro molecular weight distribution, while that of SPep was minimal, ranging between 150 and 1000 Da and primarily consisting of two to five amino acids. The cecum microflora composition of the rats was determined via 16S rDNA amplicon sequencing, showing that the SPro and SPep significantly increased the abundance and uniformity of the gut microbiota after 35 days of feeding. The Firmicutes/Bacteroidetes (F/B) ratios of the SPep, SPro, and casein groups were 2.49 ± 0.60, 2.98 ± 1.12, and 2.59 ± 0.74, respectively. Although the rats fed with SPro and SPep displayed similar gut microbiome structures, SPep significantly promoted Lactobacillus and Phascolarctobacterium growth. The results showed that SPep significantly increased the diversity of the gut microbiota and elevated the probiotic proportion. PRACTICAL APPLICATION: SPro and SPep are two nutritious and high-quality nitrogen sources. The results showed that SPro and SPep regulated the structure of gut microbiota in rats, and the effect of SPep was better. This study provides a theoretical basis for developing SPep functional foods able to regulate gut microbiota and maintain health.

Inflammatory bowel disease (IBD) develop as a result of a combination of genetic predisposition, dysbiosis of the gut microbiota, and environmental influences, which is mainly represented by ulcerative colitis (UC) and Crohn's disease (CD). IBDs can result in inflammatory hypoxia by causing intestinal inflammation and vascular damage. The hypoxia inducible factor 1-alpha (HIF-1α), as a transcription factor, can regulate the cellular adaptation to low oxygen levels and support the development and function of the gut barrier. HIF-αplays its functions through translocating into the nucleus, dimerizing with HIF-1β, and binding to hypoxia-responsive elements of HIF-1 target genes. So far, most studies have addressed the function of HIF-1α in murine models of IBD. In this review, we aim to outline the major roles of HIF-1α in the IBD. This article is protected by copyright. All rights reserved.

BACKGROUND Intestinal failure-associated liver disease (IFALD) increases mortality of patients with intestinal failure (IF), but lacks effective prevention or treatment approaches. Bile acids, gut microbiota and the host have close and complex interactions, which play a central role in modulating host immune and metabolic homeostasis. Increasing evidence suggests that derangement of the bile acid-gut microbiota (BA-GM) axis contributes to the development of IFALD. AIMS To review the BA-GM axis in the pathogenesis and clinical applications of IFALD, and to explore future directions for effective disease management. METHODS We conducted a literature search on bile acid and gut microbiota in IF and liver diseases. RESULTS The BA-GM axis demonstrates a unique IF signature manifesting as an increase in primary-to-secondary bile acids ratio, disturbed enterohepatic circulation, blunted bile acid signalling pathways, gut microbial dysbiosis, and altered microbial metabolic outputs. Bile acids and gut microbiota shape the compositional and functional alterations of each other in IF; collaboratively, they promote immune dysfunction and metabolic aberration in the liver. Diagnostic markers and treatments targeting the BA-GM axis showed promising potential in the management of IFALD. CONCLUSIONS Bile acids and gut microbiota play a central role in the development of IFALD and make attractive biomarkers as well as therapeutic targets. A multitarget, individualised therapy aiming at different parts of the BA-GM axis may provide optimal clinical benefits and requires future investigation.

The gut microbiome is increasingly recognized for its impact on host fitness, but it remains poorly understood how naturally variable environments influence gut microbiome diversity and composition. We studied changes in the gut microbiome of ten genotypes of water fleas Daphnia magna in submerged mesocosm enclosures in a eutrophic lake over a period of 16 weeks, from early summer to autumn. The microbial diversity increased when Daphnia were reintroduced from the laboratory to the lake, and the composition of gut microbes drastically changed. Both gut microbiome diversity and composition continued to change over the 16-week period, with alpha diversity peaking in late summer. The gut microbiome community was clearly distinct from that of the surrounding water, and temporal changes in the two communities were independent of each other. There were no consistent differences in the gut microbiomes among Daphnia genotypes in the lake environment. The change in gut microbiome over the season was accompanied by a decline in reproductive output and survival. There were weak, but statistically supported, effects of microbiota composition on Daphnia fitness, but there was no evidence that natural variation in microbiome diversity or composition was associated with tolerance to the cyanotoxin microcystin. We conclude that the gut microbiome of Daphnia is highly dynamic in a natural lake environment, but that host genetic effects on microbiome diversity and composition between genotypes within a population can be vanishingly small. These results emphasize that establishing the ecological effects of gut microbiota will require large-scale experiments under natural conditions. (Less)

It has been shown that whole grains and dietary fiber are important for their fermentation characteristics in the large intestine, drawing more and more attention to quinoa and quinoa polysaccharides. In this study, we evaluated the prebiotic effect of quinoa seeds and quinoa polysaccharides after human simulated digestion. The modulatory effect of the quinoa and quinoa polysaccharides (QPs) on the gut microbiota was evaluated by the in vitro fermentation using human fecal microbiota. The yield of polysaccharides extraction was 15.45%. The digestibility of the cooked and uncooked quinoa after simulation of human digestion was 69.04% and 64.09%, respectively. The effect on the microbiota composition and their metabolic products was determined by the assessment of pH, short‐chain fatty acids (SCFAs), and changes in the bacterial population. After 24 hr anaerobic incubation, the total SCFAs of cooked, uncooked quinoa, and quinoa polysaccharides were 82.99, 77.11, and 82.73 mM, respectively with a pH decrease. At the phylum, genus, and class level, it has been found that the quinoa substrates enhance the growth of certain beneficial bacteria such as Prevotella and Bacteroides. Quinoa polysaccharides can be considered prebiotic due to their ability to increase Bifidobacterium and Collinsella. Principal component analysis (PCA) showed that there was a distinct modulating effect on the fecal microbiota which represents different distribution. Our research suggests that quinoa and quinoa polysaccharides have a prebiotic potential due to their association with the positive shifts in microbiota composition and short‐chain fatty acids production, which highlights the importance of further studies around this topic., Quinoa and quinoa polysaccharides can modulate the gut microbiota. Quinoa and quinoa polysaccharides have a prebiotic effects.

The gut microbiota has a key role in the maintenance of good health, and in the pathogenesis of gastrointestinal diseases. These conditions include the inflammatory bowel diseases, colorectal cancer, coeliac disease and metabolic liver disease. Although the nature of the microbial disturbance in these conditions has not been fully characterised, this has not prevented the development of microbially based therapies. Microbial-changing therapies may address newly recognised pathophysiological contributors of disease and have the potential to replace or supplement standard therapies. Antibiotics play a role in initial Clostridiodes difficile disease and some specific inflammatory disorders. Probiotics have a more limited proven role. Faecal microbiota transplantation is of proven therapeutic benefit in recurrent C. difficile disease and ulcerative colitis. We review the current literature for microbiota-targeted therapies in gut disorders.

Aging induces significant shifts in the composition of gut microbiota associated with decreased microbial diversity. Age-related changes in gut microbiota include a loss of commensals and an increase in disease-associated pathobionts. These alterations are accelerated by lifestyle factors, such as poor nutritional habits, physical inactivity, and medications. Given that diet is one of the main drivers shaping the gut microbiota, nutritional interventions for restoring gut homeostasis are of great importance to the overall health of older adults. Polyphenols, ubiquitously present in fruits and vegetables, have emerged as promising anti-aging candidates because of their ability to modulate some of the common denominators of aging, including gut dysbiosis. These compounds can influence the composition of the gut microbiota, and gut bacteria metabolize polyphenols into bioactive compounds that produce relevant health effects. Although the role of polyphenols on the aging gut has not been fully characterized, accumulating evidence suggests that these compounds exert selective effects on the gut microbial community. Here, we discuss the reciprocal interactions between polyphenols and gut microbiota and summarize the latest findings on the effects of polyphenols on modulating intestinal bacteria during aging.

Vitamin D and its receptor are involved in health and diseases through multiple mechanisms including the immune system and gut microbiota modulations. Gut microbiota variations have huge implications in intestinal and extra-intestinal disorders such as colorectal cancer (CRC). This review highlights the preventive role of vitamin D in colorectal tumorigenesis through the effects on the immune system and gut microbiota modulation. The different associations between vitamin D, gut microbial homeostasis, immune system, and CRC, are dissected. Vitamin D is supposed to exert several chemopreventive effects on CRC including direct antineoplastic mechanisms, the effects on the immune system, and gut microbiota modulation. Large clinical studies with a randomized design, are required to confirm the role of vitamin D in CRC, confirming its key role in the complex interplay between the gut immune system and microbiota.

BACKGROUND Pomegranate is a rich source of polyphenols and has been used as a dietary supplement and pharmaceutical ingredient. This study aimed to investigate the pomegranate fruit pulp polyphenols (PFP) with regard to their anti-obesity activity and gut microbiota-modulating effect in mice. Thirty-six 4-week-old specific pathogen-free C57BL/6J mice (weight: 17.7-20.8 g) were randomly divided into three groups and fed with low-fat diet (10% fat energy), high-fat diet (HFD) (45% fat energy), or HFD supplemented with PFP by intragastric administration for 14 weeks. The obesity-related clinical indicators were investigated, and the composition of fecal microbiota was analyzed by 16S rRNA sequencing. RESULTS Our results showed that PFP treatment reduced HFD-induced body weight gain by 35.23% (P

BACKGROUND The pathophysiology of the prostate enlargement underlying lower urinary tract symptoms is unknown. Meanwhile, the gut microbiota can contribute to various host conditions. We hypothesized that the gut microbiota plays a role in prostate enlargement. METHODS We included 128 patients who underwent prostate biopsies at our hospitals between December 2018 and March 2020, excluding those who had used antibiotics within the past 6 months and those who were diagnosed with prostate cancer of cT3 or higher. Patients with prostate volumes ≥30 ml were defined as the prostate-enlargement (PE) group; those with prostate volumes

Elevated blood pressure (BP), or hypertension, is the main risk factor for cardiovascular disease. As a multifactorial and systemic disease that involves multiple organs and systems, hypertension remains a challenging disease to study. Models of hypertension are invaluable to support the discovery of the specific genetic, cellular and molecular mechanisms underlying essential hypertension, as well as to test new possible treatments to lower BP. Rodent models have proven to be an invaluable tool for advancing the field. In this review, we discuss the strengths and weaknesses of rodent models of hypertension through a systems approach. We highlight the ways how target organs and systems including the kidneys, vasculature, the sympathetic nervous system (SNS), immune system and the gut microbiota influence BP in each rodent model. We also discuss often overlooked hypertensive conditions such as pulmonary hypertension and hypertensive-pregnancy disorders, providing an important resource for researchers. LINKED ARTICLES: This article is part of a themed issue on Preclinical Models for Cardiovascular disease research (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.5/issuetoc.

Background & aims Preoperative obstructive jaundice is usually associated with higher post-operative mortality. Although external biliary drainage (EBD) has been widely used to relieve obstructive jaundice, the role of bile reinfusion after EBD is still controversial. The aim of our study was to study the effects of biliary obstruction, biliary drainage and bile reinfusion on bile acid metabolism and gut microbiota. Methods Firstly, we created a mice bile drainage collection (BDC) model to simulate the process of biliary obstruction, drainage and bile reinfusion. Then, we analysed the faecal, serum, liver and bile samples to investigate the effects of the process on bile acid profiles and gut microbiota. Finally, we evaluated the clinical effects of bile reinfusion. Results We evaluated the bile acid profiles of faeces, serum, liver and bile of normal mice. During biliary obstruction, secondary bile acids can still be produced, and increased in the liver and serum of mice. Compared with no bile reinfusion, bile reinfusion was beneficial to the recovery of T-ωMCA in the liver and bile, and can restore the colon crypt length shortened by biliary obstruction. Only Ruminococcus_1 proliferated when the biliary obstruction lasted for 12 days. In the clinic, bile reinfusion cannot accelerate the patient's perioperative recovery or prolong long-term survival. Conclusion We have successfully created a mice bile drainage collection model. Short-term bile reinfusion can partially benefit the recovery of the secondary bile acids in the liver and bile, but hardly benefit the patient's perioperative recovery or long-term survival. (247 words).

Summary As global warming intensifies, emerging evidence has demonstrated high ambient temperature during pregnancy negatively affects maternal physiology with compromised pregnant outcomes; however, little is known about the roles of gut microbiota and its underlying mechanisms in this process. Here, for the first time, we explored the potential mechanisms of gut microbiota involved in the disrupted glycolipid metabolism via hepatic mitochondrial function. Our results indicate heat stress (HS) reduces fat and protein contents and serum levels of insulin and triglyceride (TG), while increases that of non‐esterified fatty acid (NEFA), β‐hydroxybutyric acid (B‐HBA), creatinine and blood urea nitrogen (BUN) (P

Consumption of fermented food has long been associated with health benefits, but there is still limited knowledge on the bacterial dynamics in plant‐based food fermentation outside of culture‐based studies. Different fermented plant‐based products were assessed for the presence of Archaea and their microbiota bacterial dynamics during the fermentation. Archaea were consistently detected in the brine of the vegetables, and constant increase in gene copy number throughout the fermentation of kraut indicated that Archaea were not only viable but actively growing. The plant‐associated bacterial microbiota of cabbage and jalapeno were dominated by Proteobacteria, specifically Pseudomonas (51% and 39% respectively), while the okra harbored roughly equal numbers of firmicutes and proteobacteria. In cabbage and jalapeno fermentations, lactic acid bacteria (LAB), which were detected in extremely low levels in raw products, became dominant with expected succession of heterofermentative and homofermentative species. These two stages were not detected in the fermentation of okra, and Lactobacillus remained the most abundant genera. The kombucha fermentation was dominated by Gluconacetobacter as reported previously, but also characterized by high abundance of Bacteroides. Intriguingly, the microbiota composition and dynamics were very different between the two kombucha batches tested, suggesting redundancy in microorganisms’ fermentative roles. Finally, a preliminary in vitro fermentation study was indicative of a potential bifidogenic effect of microbial metabolites from kombucha. Collectively, these data indicate that fermented plant products harbor a highly diverse microbiota, bacteria, and archaea, even after the end of the fermentation.

Pu‐erh tea is very popular in Southwestern China and South Asian countries and is now becoming increasingly popular in Europe due to its well‐documented beneficial effects on human health. Pu‐erh tea aqueous extracts can maintain intestinal homeostasis. However, the mechanism of its beneficial effects on intestinal flora disorder is not clear. In this study, we focused on the effects of ripe Pu‐erh tea aqueous extracts on the intestinal microbiota in an intestinal flora disorder mouse model. Physiological indexes and the tissue section staining results showed that feeding Pu‐erh tea extract could help mice regain weight and alleviate intestinal inflammation. Further assessment of the intestinal microflora found that Pu‐erh tea extract could promote the growth of intestinal probiotics and inhibit pathogenic bacteria, thereby achieving a treatment effect for enteritis. This study provides new evidence for the therapeutic effect of Pu‐erh tea., Pu‐erh tea is very popular in Southwestern China and South Asian countries, and now is becoming more and more popular in Europe because of its well‐documented beneficial effects on human health. This study explored the mechanism of Pu‐erh tea extract in promoting human health and improving intestinal flora disorder and found that Pu‐erh tea extract can alleviate the intestinal inflammation caused by antibiotics, reduce the degree of intestinal lesions, promote the growth of intestinal probiotics and inhibit pathogenic bacteria.

Dietary soybean isoflavones (SIs) and soyasaponins (SSs) individually exert inhibitory effects on contact hypersensitivity (CHS), which is an animal model of allergic contact dermatitis (ACD); however, the beneficial effects of diets containing a mixture of SIs and SSs on CHS remain unclear. Here, we investigated the CHS‐suppressive effects of diets containing a mixture of SIs and SSs at physiologically relevant doses, and the role of the gut microbiota. The diets attenuated ear swelling and reduced the number of Gr‐1‐positive cells infiltrating the auricle tissues. Ear swelling was inhibited in the SI‐ and SS‐treated mice compared to the SI‐treated mice. Compared to the CHS controls, the levels of chemokine (C‐X‐C motif) ligand 2 and triggering receptor expressed on myeloid cells‐1 (TREM‐1) were lower in the auricle tissues of SI‐ and SS‐treated mice, whereas TREM‐1 production was not suppressed in SI‐ or SS‐treated mice. In addition, vancomycin treatment had little effect on the CHS‐inhibitory activity of SI and SS diets, whereas ciprofloxacin and metronidazole treatments blocked the effects of SI and SS diets. These antibiotics exhibited differing effects on the microbiota composition deduced from the bacterial 16S ribosomal RNA gene sequences. Therefore, consuming a mixture of SIs and SSs has ACD‐preventive effects and is affected by the gut microbiota.

Contains fulltext : 237734.pdf (Publisher’s version ) (Open Access) OBJECTIVE: Obesity is associated with impaired gut microbiota diversity, which has been linked to the development of type 2 diabetes. This study aims to examine the effects of an 8-week aerobic exercise intervention on insulin sensitivity, visceral adiposity, and gut microbiota diversity and composition in participants with obesity. METHODS: Fourteen participants (mean [SD], age 51 [11] years; BMI 34.9 [4.9] kg/m(2) ) performed an 8-week exercise intervention (2 to 4 times/week on 65% to 85% of heart rate reserve). Insulin sensitivity (hyperinsulemic euglycemic clamp), cardiorespiratory fitness (maximal oxygen uptake), visceral adiposity (dual-energy X-ray absorptiometry scan) and gut microbiota composition (16S rRNA gene sequencing) were measured before and after the intervention. RESULTS: Insulin sensitivity showed a significant increase (pre: 3.8 [1.9] mg/min/kg; post: 4.5 [1.7] mg/min/kg; p = 0.007) after training, whereas visceral adiposity decreased (pre: 959 [361] cm(3) ; post: 897 [364] cm(3) ; p = 0.02). No change in gut microbiota α- or β-diversity was found. At the genus level, the abundance of Ruminococcus gauvreauii (p = 0.02); Lachnospiraceae FCS020 group (p = 0.04), and Anaerostipes (p = 0.04) significantly increased after exercise training. Significant positive correlations were present for M-value (R. gauvreauii) and VO(2) max (R. gauvreauii and Anaerostipes). CONCLUSIONS: Eight-week exercise training in humans with obesity leads to marked improvements in insulin sensitivity and body composition and is accompanied by modest changes in 3 gut microbiome genera, all belonging to the Firmicutes phylum.

Objective The gut microbiota is a complex ecosystem that shapes host metabolism, especially in early life. Maternal vaginal and gut microbiota is vertically transmitted to offspring during natural birth. Offspring born by cesarean section (CS) do not receive these bacteria and exhibit higher obesity risk later in life. The objective of this study was to examine differences in obesity risk between offspring born naturally (NB) or by CS to lean/obese dams. Methods Lean and obese rat dams gave birth to offspring naturally or by CS. Offspring obesity risk was analyzed via body weight/composition, food intake, sucrose preference, gut microbiota, and gene expression in gut and brain tissues. Results Obese (O)+CS offspring showed greater weight gain and caloric intake but a reduction in hypothalamic agouti related neuropeptide, neuropeptide Y, and interleukin 1β expression compared with O+NB offspring. Lean (L)+CS offspring had higher serum corticosterone concentration and reduced liver peroxisome proliferator-activated receptor γ expression compared with L+NB. O+CS offspring had long-term alterations to gut microbiota, including increased relative abundance of Faecalibaculum and reduced Muribaculaceae. Conclusions Overall, CS alters obesity risk differentially based on maternal obesity status. Further studies looking at the risks of obesity associated with CS are needed, with special attention paid to maternal obesity status and gut microbiota.

Research on the Caenorhabditis elegans microbiota only recently started, with little known about how C. elegans acquires its microbiota. Slugs live in the same habitat as C. elegans and are known vectors for the worm. Hence, we wondered how the passage through a slug affects the C. elegans gut microbiota and whether worms can acquire bacteria from the slug. Using fluorescently labelled microbiota and 16S rRNA gene amplicon sequencing, we evaluated microbiota persistence and acquisition in C. elegans after slug passage. We compared C. elegans gut microbiomes isolated from wild-caught slugs to the microbiomes of worms after experimental slug passage to compare similarities and differences in microbiome composition. We found that microbiota persists in C. elegans while passing the slug gut and that worms simultaneously acquire additional bacteria species from the slug. Although the amplicon sequencing variant (ASV) richness of worms from the experiment did not exceed the richness of worms that naturally occur in slugs, we found a high number of shared ASVs indicating the importance of commonly associated microbiota. We demonstrate that C. elegans can take advantage of its passage through the slug by acquiring new potential microbiota without losing its native microbiota.

Background: This study characterized the gut microbiota and its diet‐related metabolic activity in children with intestinal failure (IF) on parenteral nutrition (PN) compared with healthy controls and in relation to disease characteristics. Methods: Serial fecal samples were collected from 15 IF patients (n = 68) and from 25 healthy children (n = 25). The fecal microbiota, and short chain fatty acids (SCFA) were measured. Results: The microbiota of patients with IF had a lower bacterial load (p = 0.003), Shannon diversity index (p

BACKGROUND AND AIM The artificial sweetener acesulfame potassium (ACK) is officially approved as safe for intake and has been used in processed foods. However, ACKs have been reported to induce metabolic syndrome, along with alteration of the gut microbiota in mice. In recent years, studies have suggested that this artificial sweetener promotes myeloperoxidase reactivity in Crohn's disease-like ileitis. We aimed to investigate the effect of ACK on the intestinal mucosa and gut microbiota of normal mice. METHODS Acesulfame potassium was administered to C57BL/6J mice (8 weeks old) via free drinking. Intestinal damage was evaluated histologically, and messenger RNA (mRNA) levels of TNF-α, IFN-γ, IL1-β, MAdCAM-1, GLP1R, and GLP2R were determined with quantitative reverse transcription polymerase chain reaction (qRT-PCR). Immunohistochemistry was performed to examine the expression of MAdCAM-1 in the small intestine. The composition of gut microbiota was assessed using high-throughput sequencing. We performed intravital microscopic observation to examine if ACK altered lymphocyte migration to the intestinal microvessels. RESULTS Acesulfame potassium increased the expression of proinflammatory cytokines, decreased the expression of GLP-1R and GLP-2R, and induced small intestinal injury with an increase in intestinal permeability, and ACK treatment induced microbial changes, but the transfer of feces alone from ACK mice did not reproduce intestinal damage in recipient mice. ACK treatment significantly increased the migration of lymphocytes to intestinal microvessels. CONCLUSION Acesulfame potassium induces dysbiosis and intestinal injury with enhanced lymphocyte migration to intestinal mucosa. Massive use of non-caloric artificial sweeteners may not be as safe as we think.

Lifestyle represents the most relevant factor for non-alcoholic fatty liver disease (NAFLD) as the hepatic manifestation of the metabolic syndrome. Although a tremendous body of clinical and preclinical data on the effectiveness of dietary and lifestyle interventions exist, the complexity of this topic makes firm and evidence-based clinical recommendations for nutrition and exercise in NAFLD difficult. The aim of this review is to guide readers through the labyrinth of recent scientific findings on diet and exercise in NAFLD and non-alcoholic steatohepatitis (NASH), summarizing "obvious" findings in a holistic manner and simultaneously highlighting stimulating aspects of clinical and translational research "beyond the obvious". Specifically, the importance of calorie restriction regardless of dietary composition and evidence from low-carbohydrate diets to target the incidence and severity of NAFLD are discussed. The aspect of ketogenesis-potentially achieved via intermittent calorie restriction-seems to be a central aspect of these diets warranting further investigation. Interactions of diet and exercise with the gut microbiota and the individual genetic background need to be comprehensively understood in order to develop personalized dietary concepts and exercise strategies for patients with NAFLD/NASH.

Human activities shape resources available to wild animals, impacting diet and probably altering their microbiota and overall health. We examined drivers shaping microbiota profiles of common cranes (Grus grus) in agricultural habitats by comparing gut microbiota and crane movement patterns (GPS-tracking) over three periods of their migratory cycle, and by analysing the effect of artificially supplemented food provided as part of a crane-agriculture management programme. We sampled faecal droppings in Russia (nonsupplemented, premigration) and in Israel in late autumn (nonsupplemented, postmigration) and winter (supplemented and nonsupplemented, wintering). As supplemented food is typically homogenous, we predicted lower microbiota diversity and different composition in birds relying on supplementary feeding. We did not observe changes in microbial diversity with food supplementation, as diversity differed only in samples from nonsupplemented wintering sites. However, both food supplementation and season affected bacterial community composition and led to increased abundance of specific genera (mostly Firmicutes). Cranes from the nonsupplemented groups spent most of their time in agricultural fields, probably feeding on residual grain when available, while food-supplemented cranes spent most of their time at the feeding station. Thus, nonsupplemented and food-supplemented diets probably diverge only in winter, when crop rotation and depletion of anthropogenic resources may lead to a more variable diet in nonsupplemented sites. Our results support the role of diet in structuring bacterial communities and show that they undergo both seasonal and human-induced shifts. Movement analyses provide important clues regarding host diet and behaviour towards understanding how human-induced changes shape the gut microbiota in wild animals.

Aims Visceral adipose tissue inflammation is a fundamental mechanism of insulin resistance in obesity and type 2 diabetes. Translocation of intestinal bacteria has been suggested as a driving factor for the inflammation. However, although bacterial DNA was detected in visceral adipose tissue of humans with obesity, it is unclear to what extent this is contamination or whether the gut microbiota is causally involved. Effects of fecal microbiota transplantation (FMT) on bacterial translocation and visceral adipose tissue inflammation in individuals with obesity and insulin resistance were assessed. Material and Methods Eight individuals with clinically severe obesity (body mass index [BMI] >35 kg/m2) and metabolic syndrome received lean donor FMT 4 weeks prior to elective bariatric surgery. The participants were age‐, sex‐, and BMI‐matched to 16 controls that underwent no fecal transplantation. Visceral adipose tissue was collected during surgery. Bacterial translocation was assessed by 16S rRNA gene sequencing of adipose tissue and feces. Pro‐inflammatory cytokine expression and histopathological analyses of visceral adipose tissue were performed to assess inflammation. Results Fecal microbiota transplantation significantly altered gut microbiota composition. Visceral adipose tissue contained a very low quantity of bacterial DNA in both groups. No difference in visceral bacterial DNA content between groups was observed. Also, visceral expression of pro‐inflammatory cytokines and macrophage infiltration did not differ between groups. No correlation between inflammatory tone and bacterial translocation was observed. Conclusions Visceral bacterial DNA content and level of inflammation were not altered upon FMT. Thus, bacterial translocation may not be the main driver of visceral adipose tissue inflammation in obesity.

Background Resveratrol, a kind of polyphenolic phytoalexin, could be obtained from numerous natural foods. Although resveratrol is demonstrated to have various bioactivities, little is known about the regulation of intestinal barrier function under immunosuppression. The present study is aimed to investigate the regulating effect of resveratrol on intestinal barrier function in immunosuppressive mice induced by cyclophosphamide. Results The effects of resveratrol on intestinal biological barrier were evaluated by 16S rRNA and metagenome sequencing analysis. The results showed that resveratrol could improve diversity of the intestinal microbiota and intestinal flora structure by increasing the abundance of probiotics, and resveratrol regulated the function of gut microbiota to resist immunosuppression. Resveratrol could significantly upregulate the secretion of secretory immunoglobulin A and promote the transcriptional levels of test cytokines, including tumor necrosis factor α, interferon-γ, interleukin-4 and interleukin-6 in jejunum and ileum mucosa, suggesting improved intestinal immune barrier by resveratrol. The mRNA and protein levels of tight junction proteins involved in intestinal physical barrier function, including ZO-1, Claudin-1 and Occludin, were increased after resveratrol treatment. The protein levels of toll like receptors 4 (TLR4), phosphorylation nuclear factor kappa-B (NF-κB-p65) and inhibitor of nuclear factor kappa-B kinase α were decreased by resveratrol treatment when compared with the untreated group, indicating the inhibition of TLR4/NF-ĸB signaling pathway. Conclusion These results provide new insights into regulation of the intestinal barrier function by resveratrol under immunosuppression and potential applications of resveratrol in recovering the intestinal function. This article is protected by copyright. All rights reserved.

As amajor by-product of mung bean processing, mung bean coat (MBC), which is rich in polyphenols and dietary fiber, is deemed to be mainly responsible for the health benefits of mung bean. However, its beneficial effects on the hyperglycemia, hyperlipidemia, and gut microbiota composition in prediabetic mice is not fully understood. The objective of this study was to investigate the efficacy of MBC in alleviating high-fat diet and streptozotocin-induced prediabetes. Herein, compared with the model control, dietary supplementation with MBC (3%, w/w) for 12 weeks significantly decreased the fasting blood glucose (24.60%), total cholesterol (15.72%), triglyceride (14.41%), and low-density lipoprotein cholesterol (22.45%). Furthermore, the improvements in glucose tolerance were reflected in the reduction of the area under the curve (AUC) and incremental AUC by approximately 23.08% and 51.18%, respectively. 16S rRNA gene sequencing of fecal microbiota suggested that MBC promoted the enrichment of beneficial bacteria (Roseburia and Bifidobacterium) and the production of short-chain fatty acids. All of the results from this study provided a scientific reference for avoiding the functional ingredients waste of MBC and expanding its application value.

Studies on large-sample gut microbial sequencing data indicate that gut microbiota can be divided into multiple community types; different community types may influence the community function and ecosystem service. However, the knowledge on the classification, diversity, interaction, and assembling of microbial community types in the gut of wild animals is still insufficient. Here, we used pika gut microbiota data as an example to study the microbial community types in large-sample sequencing dataset. Cecal microbial communities from 118 wild plateau pika (Ochotona curzoniae) individuals at 5 elevational regions on the Qinghai-Tibet Plateau were analyzed. Our results show that pika gut microbiota can be separated into 2 community types (Cluster I and Cluster II). Cluster I was mainly distributed on the high-elevation regions with more than 3694 m and was most dominated by Firmicutes. Cluster II was from the low-elevation areas (lower than 3580 m), and was predominated by Bacteroidetes. Cluster I had a higher community alpha-diversity and predicted functional diversity than Cluster II, and the beta-diversity and predicted functional profiles of these 2 clusters were significantly different. Network analysis revealed that there were more complex interactions between Cluster I, which had enhanced influence on the co-occurrences of other microbes in the bacterial community when compared to Cluster II. Phylogenetic analysis found that the environmental filtering in the Cluster I was stronger than Cluster II. The assemblages of pika gut bacterial communities were determined mainly by deterministic processes, while the relative importance of deterministic processes accounted for more percentages in the Cluster I than Cluster II. Our results demonstrated that 2 gut microbial community types in pikas had distinct diversity patterns and ecological functions. Current methods are also helpful for identifying gut community types and the related mechanisms behind gut microbiota types in large-sample sequencing data of wild animals.

Astragalus polysaccharides (APS), the main effective component of Astragalus membranaceus, can inhibit tumor growth, but the underlying mechanisms remain unclear. Previous studies have suggested that APS can regulate the gut microenvironment, including the gut microbiota and fecal metabolites. In this work, our results showed that APS could control tumor growth in melanoma‐bearing mice. It could reduce the number of myeloid‐derived suppressor cells (MDSC), as well as the expression of MDSC‐related molecule Arg‐1 and cytokines IL‐10 and TGF‐β, so that CD8+ T cells could kill tumor cells more effectively. However, while APS were administered with an antibiotic cocktail (ABX), MDSC could not be reduced, and the growth rate of tumors was accelerated. Consistent with the changes in MDSC, the serum levels of IL‐6 and IL‐1β were lowest in the APS group. Meanwhile, we found that fecal suspension from mice in the APS group could also reduce the number of MDSC in tumor tissues. These results revealed that APS regulated the immune function in tumor‐bearing mice through remodeling the gut microbiota. Next, we focused on the results of 16S rRNA, which showed that APS significantly regulated most microorganisms, such as Bifidobacterium pseudolongum, Lactobacillus johnsonii and Lactobacillus. According to the Spearman analysis, the changes in abundance of these microorganisms were related to the increase of metabolites like glutamate and creatine, which could control tumor growth. The present study demonstrates that APS attenuate the immunosuppressive activity of MDSC in melanoma‐bearing mice by remodeling the gut microbiota and fecal metabolites. Our findings reveal the therapeutic potential of APS to control tumor growth., Astragalus polysaccharides (APS) inhibit melanoma growth in mouse models. APS attenuate the immunosuppressive activity of MDSC in melanoma mice. Remodeling of the gut microbiota and fecal metabolites by APS induce anti–tumor immunity.

Hyperlipidemia an immense group of acquired or genetic metabolic disorders that is characterized by an excess of lipids in the bloodstream. Altogether, they have a high prevalence worldwide and constitute a major threat to human health. Glycosaminoglycans (GAG) are natural biomolecules that have hypolipidemic activity. The purpose of this study was to investigate the potential hypolipidemic effect of glycosaminoglycans extracted from Ostrea rivularis (OGAG) on hyperlipidemic zebrafish, as well as the possible underlying mechanism of such effect. Dietary supplementation with OGAG during 4 weeks significantly reduced the serum and hepatic lipid levels and the hepatosomatic index in hyperlipidemic zebrafish. In addition, histopathological showed that OGAG supplementation decreases the volume and number of lipid droplets in hepatocytes. Transcriptome and real‐time quantitative polymerase chain reaction analysis revealed that the gene expression levels of PPARγ, SCD, HMGRA, ACAT2, HMGCS, and HMGCR were significantly downregulated by OGAG treatment in hepatocytes, whereas those of CD36, FABP2, FABP6, ABCG5, and CYP7A1 were significantly upregulated. This suggests that the hypolipidemic effect of OGAG relies on increasing the ketogenic metabolism of fatty acids, inhibiting cholesterol synthesis, and enhancing the transformation of cholesterol to bile acid. Furthermore, OGAG treatment improved gut microbiota imbalance by reducing the Firmicutes‐to‐Bacteroidetes ratio, increasing the relative abundance of beneficial bacteria (Bacteroidetes, Verrucomicrobia, Acidobacteria, and Sphingomonas), and reducing the relative abundance of harmful bacteria (Proteobacteria, Cohaesibacter, Vibrio, and Terrisporobacter). These findings highlight the potential benefit of implementing OGAG as a dietary supplement to prevent and treat hyperlipidemia.

This study evaluated the effects of flours from four different sweet potato root (SPR) varieties, being two with white peel and two with purple peel, on the composition and metabolic activity of human colonic microbiota in vitro. The capability of these SPR flours (20 g/L) to cause alterations in relative abundance of different bacterial groups found as part of human colonic microbiota, as well as in lactic acid and short-chain fatty acid production was evaluated during 48 hr of an in vitro colonic fermentation. The SPR flours were submitted to a simulated gastrointestinal digestion prior to use in experiments. The four SPR flours increased the relative abundance of Lactobacillus/Enterococcus (range: 0.49-4.48%) and Bifidobacterium (range: 0.32-3.27%) and decreased the relative abundance of Bacteroides/Prevotella (range: 0.29-7.49%), Clostridium histolyticum (range: 0.15-2.08%), and Eubacterium rectale/Clostridium coccoides (range: 0.28-3.86%) during the 48 hr of colonic fermentation. The four SPRF flours had positive prebiotic indexes (> 0.38) after 24 and 48 hr of colonic fermentation, reinforcing the occurrence of selective stimulatory effects on colonic microbiota. An increased metabolic activity of human colonic microbiota was caused by tested SPR flours, which was evidenced by decreased pH (range: 3.20-3.83) and increased lactic acid and short chain fatty acid production during the 48 hr of colonic fermentation. The four examined SPR flours were capable of causing positive alterations in composition and driving the metabolic activity of human colonic microbiota during in vitro colonic fermentation, which should be linked to their prebiotic properties. PRACTICAL APPLICATION: The four examined sweet potato root flours (SPRF) caused beneficial alterations in composition besides of driving the metabolic activity of human colonic microbiota in vitro. These results characterize the examined SPRF as candidates for use as prebiotic ingredients by food industry for formulation of value-added functional foods or dietary supplements.

BACKGROUND Oleanolic acid (OA) is a pentacyclic triterpenoid compound that is present at high levels in olive oil and has several promising pharmacological effects, such as liver protection and anti-inflammatory, antioxidant, and anticancer effects. The purpose of the present study was to assess whether OA treatment affects gut health compared to a control condition, including gut microbiota and intestinal epithelial immunity. RESULTS Illumina MiSeq sequencing (16S rRNA gene) was used to investigate the effect of OA on the microbial community of the intestinal tract, while Illumina HiSeq (RNA-seq) technology was used to investigate the regulatory effect of OA on gene expression in intestinal epithelial cells, which allowed for a comprehensive analysis of the effects of OA on intestinal health. The results showed that the consumption of OA initially controlled weight gain in mice and altered the composition of the gut microbiota. At the phylum level, OA significantly increased the relative abundances of cecum Firmicutes but decreased the abundance of Actinobacteria, and at the genus level it increased the relative abundance of potentially beneficial bacteria such as Oscillibacter and Ruminiclostridium 9. Oleanolic acid treatment also altered the expression of 12 genes involved in the Kyoto Encyclopedia of Genes and Genomes（KEGG）pathways of complement and coagulation cascades, hematopoietic cell lineage, and leukocyte transendothelial migration in intestinal epithelial cells to improve gut immunity. CONCLUSION Intake of OA can contribute beneficial effects by optimizing gut microbiota and altering the immune function of intestinal epithelial cells, potentially to improve intestinal health status. © 2021 Society of Chemical Industry.

Herb pairs are the unique combinations of two relatively fixed herbs, intrinsically convey the basic idea of traditional Chinese medicine prescriptions. The compatibility of Radix ginseng and Schisandra chinensis has been used in traditional Chinese medicine for treating Alzheimer's disease for many years. However, there are few studies on Radix ginseng-Schisandra chinensis herb pair, and the underlying action mechanism is still unclear. In this study, the mechanism of Radix ginseng-Schisandra chinensis herb pair on Alzheimer's disease was investigated by using mass spectrometry-based urinary metabolomics method. 16 urinary endogenous metabolites were identified as potential biomarkers. Meanwhile, 10 biomarkers were quantified with tandem mass spectrometry. The study result showed that the brain pathologic symptoms of model rats were improved and the potential biomarkers were adjusted backwards significantly after the herb pair administration. The metabolic pathways linked to the herb pair-regulated endogenous biomarkers included phenylalanine and tyrosine metabolism, tryptophan metabolism, purine metabolism, and so on. The above metabolic pathways reflected that Radix ginseng-Schisandra chinensis herb pair mainly regulates abnormal energy metabolism, reduces inflammation and regulates gut microbiota and neurotransmitters in the treatment of Alzheimer's disease. This article is protected by copyright. All rights reserved.

Increasing dietary fiber intake is considered to be an effective way to prevent and relieve the diseases associated with high-income lifestyles. Compared with soluble dietary fiber, comprehensive evaluation about the effects of insoluble dietary fiber on hyperlipidemia is rarely studied. In the present study, the insoluble dietary fiber was extracted from defatted rice bran by enzymatic treatments (IDF-dRB), followed by investigation about the adsorption and antioxidant activities in vitro. Moreover, the alleviating effects of IDF-dRB on hyperlipidemia were evaluated and analyzed. As a result, IDF-dRB possessed good adsorption capacities of glucose and cholesterol, and also exhibited excellent properties in scavenging radicals. Furthermore, intervention with IDF-dRB significantly improved lipid and glucose metabolism and alleviated inflammation and oxidative stress in rats fed high-fat diet. It was also observed that IDF-dRB treatment could recover the decline in species of gut microbiota caused by high fat diet, increase the community richness, and modulate the metabolic function of gut microbiota. In conclusion, the results indicated that IDF-dRB could ameliorate hyperlipidemia from many aspects and offered some perspectives about the effects of diet intervention with insoluble dietary fiber. PRACTICAL APPLICATION: Rice bran and defatted rice bran are coproducts in the rice processing industry and potentially valuable for the preparation of insoluble dietary fiber. Here an insoluble dietary fiber IDF-dRB was extracted from defatted rice bran and showed good properties in improving lipid and glucose levels, alleviating inflammation and oxidative stress, and modulating gut microbiota in rats fed high-fat diet, suggesting the potential application in ameliorating hyperlipidemia.

Vertebrates harbour gut microbial communities containing hundreds of bacterial species, most of which have never been cultivated or isolated in the laboratory. The lack of cultured representatives from vertebrate gut microbiotas limits the description and experimental interrogation of these communities. Here, we show that representatives from >50% of the bacterial genera detected by culture-independent sequencing in the gut microbiotas of fence lizards, house mice, chimpanzees, and humans were recovered in mixed cultures from frozen faecal samples plated on a panel of nine media under a single growth condition. In addition, culturing captured >100 rare bacterial genera overlooked by culture-independent sequencing, more than doubling the total number of bacterial sequence variants detected. Our approach recovered representatives from 23 previously uncultured candidate bacterial genera, 12 of which were not detected by culture-independent sequencing. Results identified strategies for both indiscriminate and selective culturing of the gut microbiota that were reproducible across vertebrate species. Isolation followed by whole-genome sequencing of 161 bacterial colonies from wild chimpanzees enabled the discovery of candidate novel species closely related to the opportunistic pathogens of humans Clostridium difficile and Hungatella hathewayi. This study establishes culturing methods that improve inventories and facilitate isolation of gut microbiota constituents from a wide diversity of vertebrate species.