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Gut microbiota plays an important role in metabolic homeostasis. Previous studies demonstrated that ginsenoside Rb1 might improve obesity-induced metabolic disorders through regulating glucose and lipid metabolism in the liver and adipose tissues. Due to low bioavailability and enrichment in the intestinal tract of Rb1, we hypothesized that modulation of the gut microbiota might account for its pharmacological effects as well. Here, we show that oral administration of Rb1 significantly decreased serum LDL-c, TG, insulin, and insulin resistance index (HOMA-IR) in mice with a high-fat diet (HFD). Dynamic profiling of the gut microbiota showed that this metabolic improvement was accompanied by restoring of relative abundance of some key bacterial genera. In addition, the free fatty acids profiles in feces were significantly different between the HFD-fed mice with or without Rb1. The content of eight long-chain fatty acids (LCFAs) was significantly increased in mice with Rb1, which was positively correlated with the increase of Akkermansia and Parasuttereller , and negatively correlated with the decrease of Oscillibacter and Intestinimonas. Among these eight increased LCFAs, eicosapentaenoic acid (EPA), octadecenoic acids, and myristic acid were positively correlated with metabolic improvement. Furthermore, the colonic expression of the free fatty acid receptors 4 (Ffar4) gene was significantly upregulated after Rb1 treatment, in response to a notable increase of LCFA in feces. These findings suggested that Rb1 likely modulated the gut microbiota and intestinal free fatty acids profiles, which should be beneficial for the improvement of metabolic disorders in HFD-fed mice. This study provides a novel mechanism of Rb1 for the treatment of metabolic disorders induced by obesity, which may provide a therapeutic avenue for the development of new nutraceutical-based remedies for treating metabolic diseases, such as hyperlipidemia, insulin resistance, and type 2 diabetes. [ABSTRACT FROM AUTHOR]

Objective: Gut microbial dysbiosis is associated with high heterogeneity of polycystic ovary syndrome (PCOS); however, studies about gut microbiota targeted clinical intervention in PCOS are limited. Our study aimed to evaluate the effects of high-fiber diet or combined with acarbose on the clinical phenotypes of PCOS, focusing on the possible influence of gut microbiota in this process. Methods: Twenty-five patients with PCOS were recruited and randomly divided into two groups, W group (n = 14) received the WTP diet (a high-fiber diet composed of whole grains, traditional Chinese medicinal foods, and prebiotics), and A group (n = 11) received the WTP diet combined with acarbose. The follow-up time was 12 weeks. The sex hormonal and glycolipid metabolic parameters, inflammatory factors, brain–gut peptides, and alteration of gut microbiota were evaluated. Results: The PCOS clinical phenotypes, inflammatory state, and brain–gut peptides secretion were all alleviated in both groups, while the hyperandrogenism, insulin resistance, and brain–gut peptides secretion were better improved in the A group. Alpha and beta diversities were altered more significantly in the A group. Amplicon sequence variants (ASVs) were clustered into 14 co-abundant groups (CAGs) as potential functional groups that may respond to the intervention. The CAGs predominantly comprised of Bifidobacterium and Lactobacillus were more enriched, while the CAGs predominantly comprised of Bacteroides vulgatus , Alistipes , Blautia , Lachnospira , and Roseburia were more inhibited in the A group than in W group. Moreover, the CAGs enriched in the A group had a stronger negative correlation with the luteinizing hormone (LH)/follicle-stimulating hormone (FSH) ratio, testosterone, homeostasis model assessment-insulin resistance (HOMA-IR), α-1-acid glycoprotein (α-AGP), and leptin, and positive correlation with adiponectin and spexin, while the CAGs inhibited showed an opposite trend. Conclusions: High-fiber diet could alleviate the chronic metabolic inflammation, reproductive function, and brain–gut peptides secretion of patients with PCOS, and high-fiber diet combined with acarbose could better improve the PCOS clinical phenotypes. The remodeling of gut microbiota by our intervention may play an important role in these improvements. Clinical Trial Registration: http://www.chictr.org.cn/showproj.aspx?proj=4500 , ChiCTR-TRC-14005075 [ABSTRACT FROM AUTHOR]

Familial hypercholesterolemia (FH) is an inherited rare disease leading to markedly elevated low-density lipoprotein cholesterol (LDL-C) levels and increased risk for cardiovascular event. Gut microbiota has been implicated as a pivotal contributing factor in hyperlipidemia, however, its role in FH remains elusive. We performed whole-exome and metagenomics sequencing on a family with 22 members in which myocardial infarctions occurred at a young age with unclear etiology. We confirmed the missense mutation of LDLR c.1723C>T accounted for the abnormal cholesterol metabolism in the family through co-segregation analysis. In addition, Prevotella dentalis was found elevated and strongly associated with LDL-C level in FH family members with mutation of LDLR c.1723C>T compared to unaffected members with hyperlipidemia. Overall, our work suggests that whole-exome sequencing can facilitate identification of disease-causing variants and enable preventive treatment of FH. Our metagenomics analysis provides early insights into potential contributions of host-microbe interactions in genetic and common hypercholesterolemia. [ABSTRACT FROM AUTHOR]

Gut microbiota (GM) dysbiosis has been considered a pathogenic origin of many chronic diseases. In our previous trial, a shift in GM structure caused by a complex fiber-rich diet was associated with the health improvement of obese Prader-Willi syndrome (PWS) children. The pre- and post-intervention GMs (pre- and post-group, respectively) from one child were then transplanted into gnotobiotic mice, which resulted in significantly different physiological phenotypes, each of which was similar to the phenotype of the corresponding GM donor. This study was designed to investigate the miRNA-gene regulatory networks involved in causing these phenotypic differences. Using the post-group as a reference, we systematically identified and annotated the differentially expressed (DE) miRNAs and genes in the colon and liver of the pre-group in the second and fourth weeks after GM inoculation. Most of the significantly enriched GO terms and KEGG pathways were observed in the liver and were in the second week after GM transplantation. We screened 23 key genes along with their 73 miRNA regulators relevant to the host phenotype changes and constructed a network. The network contained 92 miRNA-gene regulation relationships, 51 of which were positive, and 41 of which were negative. Both the colon and liver had upregulated pro-inflammatory genes, and genes involved in fatty acid oxidation, lipolysis, and plasma cholesterol clearance were downregulated in only the liver. These changes were consistent with lipid and cholesterol accumulation in the host and with a high inflammation level. In addition, the colon showed an impacted glucagon-like peptide 1 (GLP-1) signaling pathway, while the liver displayed decreased insulin receptor signaling pathway activity. These molecular changes were mainly found in the second week, 2 weeks before changes in body fat occurred. This time lag indicated that GM dysbiosis might initially induce cholesterol and lipid metabolism-related miRNA and gene expression disorder and then lead to lipid accumulation and obesity development, which implicates a causative role of GM dysbiosis in obesity development rather than a result of obesity. This study provides fundamental molecular information that elucidates how dysbiotic GM increases host inflammation and disturbs host lipid and glucose metabolism. [ABSTRACT FROM AUTHOR]

Akkermansia muciniphila is potential probiotic in that its type strain ATCC BAA-835 has beneficial effects upon obesity and diabetes. However, whether A. muciniphila can improve inflammatory bowel diseases (IBD), which is a form of chronic intestinal dysbiosis, is unknown. Hence, we used an isolated murine A. muciniphila strain (designated 139) and A. muciniphila type strain ATCC, to investigate their anti-inflammatory properties in cell models and in Dextran Sulfate Sodium (DSS)-induced chronic colitis of mice. In vitro , the two A. muciniphila strains exerted similar anti-inflammatory properties as they both reduced IL-8 production by TNF-α-stimulated HT-29 cells. However, neither of the strains showed capacity to increase the differentiation of regulatory T (Treg)-cells from CD4+ T cell populations significantly. In vivo , both A. muciniphila strains exerted anti-inflammatory effects on chronic colitis as they improved clinical parameters including spleen weight, colon inflammation index, and colon histological score. They also down-regulated the expression of the pro-inflammatory cytokines including TNF-α and IFN-γ in the colon of mice. However, the anti-inflammatory effects of strain ATCC were stronger than strain 139 in that ATCC significantly reduced spleen weight, colon inflammation index, and fecal lipocalin-2 content in mice with chronic colitis, while strain 139 was not. Dysbiosis of the gut microbiota was observed in mice with chronic colitis. Both A. muciniphila strains facilitated the normalization of the gut microbiota. The specific capacity of strain ATCC to modulate the differentiation of Tregs as well as increase production of short chain fatty acids, demonstrated strain-specific characteristics for these two A. muciniphila strains. This study suggests the potential beneficial effect of A. muciniphila on IBD and the importance of the future study of the function of A. muciniphila at the strain-level. [ABSTRACT FROM AUTHOR]

Chronic inflammation induced by endotoxin from a dysbiotic gut microbiota contributes to the development of obesity-related metabolic disorders. Modification of gut microbiota by a diet to balance its composition becomes a promising strategy to help manage obesity. A dietary scheme based on whole grains, traditional Chinese medicinal foods, and prebiotics ( WTP diet) was designed to meet human nutritional needs as well as balance the gut microbiota. Ninety-three of 123 central obese volunteers ( BMI ≥ 28 kg m−2) completed a self-controlled clinical trial consisting of 9-week intervention on WTP diet followed by a 14-week maintenance period. The average weight loss reached 5.79 ± 4.64 kg (6.62 ± 4.94%), in addition to improvement in insulin sensitivity, lipid profiles, and blood pressure. Pyrosequencing of fecal samples showed that phylotypes related to endotoxin-producing opportunistic pathogens of Enterobacteriaceae and Desulfovibrionaceae were reduced significantly, while those related to gut barrier-protecting bacteria of Bifidobacteriaceae increased. Gut permeability, measured as lactulose/mannitol ratio, was decreased compared with the baseline. Plasma endotoxin load as lipopolysaccharide-binding protein was also significantly reduced, with concomitant decrease in tumor necrosis factor-α, interleukin-6, and an increase in adiponectin. These results suggest that modulation of the gut microbiota via dietary intervention may enhance the intestinal barrier integrity, reduce circulating antigen load, and ultimately ameliorate the inflammation and metabolic phenotypes. [ABSTRACT FROM AUTHOR]

Supplementation of probiotics is a promising gut microbiota-targeted therapeutic method for hyperlipidemia and atherosclerosis. However, the selection of probiotic candidate strains is still empirical. Here, we obtained a human-derived strain, Lactobacillus mucosae A1, which was shown by metagenomic analysis to be promoted by a high-fiber diet and associated with the amelioration of host hyperlipidemia, and validated its effect on treating hyperlipidemia and atherosclerosis as well as changing structure of gut microbiota in ApoE-/- mice on a Western diet. L. mucosae A1 attenuated the severe lipid accumulation in serum, liver and aortic sinus of ApoE-/- mice on a Western diet, while it also reduced the serum lipopolysaccharide-binding protein content of mice, reflecting the improved metabolic endotoxemia. In addition, L. mucosae A1 shifted the gut microbiota structure of ApoE-/- mice on a Western diet, including recovering a few members of gut microbiota enhanced by the Western diet. This study not only suggests the potential of L. mucosae A1 to be a probiotic in the treatment of hyperlipidemia and atherosclerosis, but also highlights the advantage of such function-based rather than taxonomy-based strategies for the selection of candidate strains for the next generation probiotics. [ABSTRACT FROM AUTHOR]