Metformin is commonly used as the first line of medication for the treatment of metabolic syndromes, such as obesity and type 2 diabetes (T2D). Recently, metformin-induced changes in the gut microbiota have been reported; however, the relationship between metformin treatment and the gut microbiota remains unclear. In this study, the composition of the gut microbiota was investigated using a mouse model of high-fat-diet (HFD)-induced obesity with and without metformin treatment. As expected, metformin treatment improved markers of metabolic disorders, including serum glucose levels, body weight, and total cholesterol levels. Moreover, Akkermansia muciniphila (12.44% ± 5.26%) and Clostridium cocleatum (0.10% ± 0.09%) abundances increased significantly after metformin treatment of mice on the HFD. The relative abundance of A. muciniphila in the fecal microbiota was also found to increase in brain heart infusion (BHI) medium supplemented with metformin in vitro . In addition to the changes in the microbiota associated with metformin treatment, when other influences were controlled for, a total of 18 KEGG metabolic pathways (including those for sphingolipid and fatty acid metabolism) were significantly upregulated in the gut microbiota during metformin treatment of mice on an HFD. Our results demonstrate that the gut microbiota and their metabolic pathways are influenced by metformin treatment.

Nonalcoholic fatty liver disease (NAFLD) is associated with obesity but also found in non-obese individuals. Gut microbiome profiles of 171 Asians with biopsy-proven NAFLD and 31 non-NAFLD controls are analyzed using 16S rRNA sequencing; an independent Western cohort is used for external validation. Subjects are classified into three subgroups according to histological spectra of NAFLD or fibrosis severity. Significant alterations in microbiome diversity are observed according to fibrosis severity in non-obese, but not obese, subjects. Ruminococcaceae and Veillonellaceae are the main microbiota associated with fibrosis severity in non-obese subjects. Furthermore, stool bile acids and propionate are elevated, especially in non-obese subjects with significant fibrosis. Fibrosis-related Ruminococcaceae and Veillonellaceae species undergo metagenome sequencing, and four representative species are administered in three mouse NAFLD models to evaluate their effects on liver damage. This study provides the evidence for the role of the microbiome in the liver fibrosis pathogenesis, especially in non-obese subjects.

Human papillomavirus (HPV) is the most important causative agent of cervical cancers worldwide. However, our understanding of how the vaginal microbiota might be associated with HPV infection is limited. In addition, the influence of human genetic and physiological factors on the vaginal microbiota is unclear. Studies on twins and their families provide the ideal settings to investigate the complicated nature of human microbiota. This study investigated the vaginal microbiota of 68 HPV-infected or uninfected female twins and their families using 454-pyrosequencing analysis targeting the variable region (V2–V3) of the bacterial 16S rRNA gene. Analysis of the vaginal microbiota from both premenopausal women and HPV-discordant twins indicated that HPV-positive women had significantly higher microbial diversity with a lower proportion of Lactobacillus spp. than HPV-negative women. Fusobacteria, including Sneathia spp., were identified as a possible microbiological marker associated with HPV infection. The vaginal microbiotas of twin pairs were significantly more similar to each other than to those from unrelated individuals. In addition, there were marked significant differences from those of their mother, possibly due to differences in menopausal status. Postmenopausal women had a lower proportion of Lactobacillus spp. and a significantly higher microbiota diversity. This study indicated that HPV infection was associated with the composition of the vaginal microbiota, which is influenced by multiple host factors such as genetics and menopause. The potential biological markers identified in this study could provide insight into HPV pathogenesis and may represent biological targets for diagnostics.

We evaluated immunometabolic functions of novel Lactobacillus fermentum strains (KBL374 and KBL375) isolated from feces of healthy Koreans. The levels of inflammatory cytokines, such as interleukin (IL)-2, interferon-γ, IL-4, IL-13, and IL-17A, were decreased, and that of the anti-inflammatory cytokine IL-10 was increased, in human peripheral blood mononuclear cells (PBMCs) treated with the L. fermentum KBL374 or KBL375 strain. When these strains were orally administered to mice with dextran sulfate sodium (DSS)-induced colitis, both L. fermentum KBL374 and KBL375 showed beneficial effects on body weight, disease activity index score, colon length, cecal weight, and histological scores. Furthermore, both L. fermentum KBL374 and KBL375 modulated the innate immune response by improving gut barrier function and reducing leukocyte infiltration. Consistent with the PBMC data, both L. fermentum KBL374- and KBL375-treated DSS mice demonstrated decreased Th1-, Th2-, and Th17-related cytokine levels and increased IL-10 in the colon compared with the DSS control mice. Administration of L. fermentum KBL374 or KBL375 to mice increased the CD4+CD25+Foxp3+Treg cell population in mesenteric lymph nodes. Additionally, L. fermentum KBL374 or KBL375 administration reshaped and increased the diversity of the gut microbiota. In particular, L. fermentum KBL375 increased the abundance of beneficial microorganisms, such as Lactobacillus spp. and Akkermansia spp. Both L. fermentum KBL374 and KBL375 may alleviate inflammatory diseases, such as inflammatory bowel disease, in the gut by regulating immune responses and altering the composition of gut microbiota.