Gegen Qinlian Decoction (GQD), a traditional Chinese medicine (TCM) formula, has long been used for the treatment of common metabolic diseases, including type 2 diabetes mellitus. However, the main limitation of its wider application is ingredient complexity of this formula. Thus, it is critically important to identify the major active ingredients of GQD and to illustrate mechanisms underlying its action. Here, we compared the effects of GQD and berberine, a hypothetical key active pharmaceutical ingredient of GQD, on a diabetic rat model by comprehensive analyses of gut microbiota, short-chain fatty acids, proinflammatory cytokines, and ileum transcriptomics. Our results show that berberine and GQD had similar effects on lowering blood glucose levels, modulating gut microbiota, inducing ileal gene expression, as well as relieving systemic and local inflammation. As expected, both berberine and GQD treatment significantly altered the overall gut microbiota structure and enriched many butyrate-producing bacteria, including Faecalibacterium and Roseburia, thereby attenuating intestinal inflammation and lowering glucose. Levels of short-chain fatty acids in rat feces were also significantly elevated after treatment with berberine or GQD. Moreover, concentration of serum proinflammatory cytokines and expression of immune-related genes, including Nfkb1, Stat1, and Ifnrg1, in pancreatic islets were significantly reduced after treatment. Our study demonstrates that the main effects of GQD can be attributed to berberine via modulating gut microbiota. The strategy employed would facilitate further standardization and widespread application of TCM in many diseases.

Microbiome research is a quickly developing field in biomedical research, and we have witnessed its potential in understanding the physiology, metabolism and immunology, its critical role in understanding the health and disease of the host, and its vast capacity in disease prediction, intervention and treatment. However, many of the fundamental questions still need to be addressed, including the shaping forces of microbial diversity between individuals and across time. Microbiome research falls into the classical nature vs. nurture scenario, such that host genetics shape part of the microbiome, while environmental influences change the original course of microbiome development. In this review, we focus on the nature, i.e., the genetic part of the equation, and summarize the recent efforts in understanding which parts of the genome, especially the human and mouse genome, play important roles in determining the composition and functions of microbial communities, primarily in the gut but also on the skin. We aim to present an overview of different approaches in studying the intricate relationships between host genetic variations and microbes, its underlying philosophy and methodology, and we aim to highlight a few key discoveries along this exploration, as well as current pitfalls. More evidence and results will surely appear in upcoming studies, and the accumulating knowledge will lead to a deeper understanding of what we could finally term a “hologenome”, that is, the organized, closely interacting genome of the host and the microbiome.

Functional constipation is a gastrointestinal disorder that affects millions of people and is correlated with gut microbiome dysbiosis. The currently available treatments are ineffective; therefore, novel treatment schemes targeting the gut microbiome are desired. The aim of this study was to assess the effects of yogurt supplemented with seven probiotic strains and six types of dietary fibers on functional constipation. In the mouse study, mice with induced constipation were administered the yogurt once a day for 1 wk, with fecal parameters and intestinal transit rate measured. In the clinical study, participants with constipation (N = 86) were given the yogurt once daily (200 g) for 4 wk. Fecal and blood samples along with Patient Assessment of Constipation-symptoms and Patient Assessment of Constipation-Quality of Life Scale questionnaires were collected to evaluate the safety and efficacy of the yogurt. Shotgun metagenomic sequencing was performed to analyze fecal samples of both mice and humans. We found that constipated mice had different gut microbiomes compared with those in healthy controls; yogurt treatment significantly relieved constipation-related symptoms and resulted in shifts in the microbiome. Yogurt also relieved symptoms of antibiotic-induced constipation in mice and restored the gut microbiome to a certain extent. In the clinical trial with 86 patients, yogurt administration significantly improved constipation symptoms and showed no serious adverse effects (was generally considered safe). However, subsequent metagenomic profiling of the gut microbiome did not reveal significant changes in the microbial composition, in contrast to the results in mice. We hypothesize that the differences in dosage between mice and humans may attribute to such discrepancies, and microbiome changes may not be necessary for improvements of constipation symptoms in humans. Results from this study showed that yogurt can potentially be used for the treatment of constipation.

Background: High genetic variability at the reverse transcriptase (RT) region of HBV could confer resistance to nucleoside/nucleotide analogues (NUCs). The aim of this study was to identify new RT amino acid (AA) substitutions related to NUC resistance. Methods: HBV RT sequences of genotype C from 501 chronic hepatitis B (CHB) patients were analysed to identify potential RT substitutions related to NUC resistance. In vitro studies without and with NUCs were performed in a HepG2 cell line transfected by clones with RT harbouring wild-type or substituted AA(s) of interest. Results: Among 261 NUC-treated CHB patients, we found a high detection rate of rtM204I/V substitution (30.7% [80/261]). We identified a new substitution of rtH55R, and its detection rate had a significantly increasing trend from 3.8% (9/240) in the untreated group to 7.2% (13/181) or 33.8% (27/80) in the treated group with rtM204 or with rtM204I/V substitutions ( P<0.0001). In vitro studies showed that rtH55R had a similar HBV DNA level compared to wild type. The rtH55R+rtM204I clone had a significantly better replication capacity than the rtM204I clone without NUCs ( P<0.05). The replication capacity of the rtM204I clone was found to significantly decrease under lamivudine treatment, but this was not found in the rtH55R+rtM204I clone. Conclusions: We identified a new HBV RT substitution of rtH55R in genotype-C-infected CHB patients. It is frequently found in combination with rtM204I/V substitution under NUC treatment. In vitro studies suggest that it might play some replication compensatory role in rtM204I mutants under lamivudine treatment.

Background: The serum hepatitis B virus (HBV) RNA is suggested as a potential new biomarker of HBV infection. However, it is not fully understood. Objectives: The current study aimed at characterizing serum HBV RNA in patients with untreated chronic hepatitis B (CHB) and genotype B and C HBV infection. Methods: A large cohort of 483 patients with hepatitis B e antigen (HBeAg)-positive and -negative was performed. The routine serum biomarkers of HBV infection were tested. HBV genotyping was carried out by direct sequencing. Serum HBV RNA levels were quantified using a method described in the authors’ previous study (lower limit of detection: 66.7 IU/mL). Results: Serum HBV RNA was detected in 92.5% (394/426) of the patients with HBeAg-positive and 31.6% (18/57) of HBeAg-negative ones; a positive association was observed between HBeAg and HBV RNA statuses in the subjects. Alanine aminotransferase (ALT), HBV DNA, and genotype were the independent predictors in patients with HBeAg-positive CHB (P = 0.024, 0.001 and 0.014, respectively), while it was HBV DNA in the negative ones (P = 0.000) for serum HBV RNA detectability. Serum HBV RNA was positively correlated with ALT, aspartate transaminase (AST) and HBV DNA, regardless of HBeAg status, and with hepatitis B surface antigen (HBsAg) in HBeAg-positive ones (P < 0.05). Conclusions: Serum HBV RNA may be affected by HBeAg status, serum HBV DNA, HBsAg levels, HBV genotype, ALT, and AST levels. There might be some similarities between the characteristics of serum HBV RNA, and serum HBV DNA and HBsAg, regardless of its distinctive features. The roles of serum HBV RNA in viral replication, infection, survival, disease progression, and antiviral responses need to be investigated in further studied. Keywords: Hepatitis B Virus; Serum HBV RNA; Biomarker; Chronic Hepatitis B; Genotype