Berberine (BBR) is an isoquinoline alkaloid that is widely distributed in the plant kingdom and is commonly found in Coptis chinensis Franch. It has low bioavailability, but it can interact with gut microbiota and affect a variety of diseases. The effects of BBR in diabetes, hyperlipidemia, atherosclerosis, liver diseases, intestinal diseases, mental disorders, autoimmune diseases, and other diseases are all thought to be related to gut microbiota. This review systematically and comprehensively summarize these interactions and their effects, and describes the changes of gut microbiota after the intervention of different doses of berberine and its potential clinical consequences, in order to provide a basis for the rational application of BBR in the future clinical treatment.

Background: To investigate the correlation between gut microbiota and circulating microRNAs (miRNAs) in patients with primary diagnosis of type 2 diabetes mellitus (T2DM) and to explore the possible mechanisms of miRNA-gut microbiota crosstalke network in the regulation of the insulin signaling pathway and glucose homeostasis in T2DM. Methods: T2DM patients and normal controls were recruited. Fasting plasma and fecal samples were collected from the subjects, and their biochemical indexes including fasting blood glucose (FBG), glycated hemoglobin (HbAlc), cholesterol (TC), total triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and insulin were recorded. The variations in intestinal microbiota in the two groups were analyzed using 16S rRNA third-generation sequencing technology, and the differential expression of miRNAs between the groups was screened using miRNA high-throughput sequencing. The correlation and association between specifically changed intestinal microbiota and miRNA expressions were analyzed using a combination of bioinformatics analysis and statistical methods. Finally, 16S functional gene prediction analysis and target gene enrichment pathway analysis were carried out to predict relevant gut microbiota and miRNAs. Results: Compared with normal controls, the biochemical indexes of HAlbc, FBG, TG, TC, LDL, HDL, and insulin were significantly different in T2DM patients (P<0.001, P<0.001, P=0.0125, P=0.98, P<0.001 P=0.022, and P=0.0013, respectively). The two groups also showed significantly different intestinal microbiota distribution and miRNA expression characteristics, including in the counts of Bacteriodes. uniformis and Phascolarctobacterium. Faecium (P=0.023, 0.031), which were negatively correlated (P=0.014, FC = -2.36) with the expression levels of serum miR-122-5p (r=−0.68, −0.60, P=0.01, 0.01). Conclusions: This study discovered specific gut microbiota and miRNA characteristics in patients with a primary diagnosis of T2DM. A negative correlation between miR-122-5p and the intestinal bacteria Bacteriodes. uniformis and Phascolarctobacterium. Faecium was also revealed, suggesting that the crosstalke between miRNA and gut microbiota may regulate the insulin secretion and signal transduction by controling key genes of glucose metabolism during the development of T2DM.

Original Article Correlation between gut bacteria Phascolarctobacterium and exogenous metabolite α-linolenic acid in T2DM: a case-control study Weidong Li, Lisha Li, Fujie Yang, Qiongying Hu, Daqian Xiong

Programmed cell death 1 ligand (PD‐L1) and its receptor (PD‐1) are key molecules for immunoregulation and immunotherapy. PD‐L1 binding PD‐1 is an effective way to regulate T or B cell immunity in autoimmune diseases such as rheumatoid arthritis (RA). In our study, we overexpressed PD‐L1 by constructing a recombinant of PD‐L1‐lentiviral vector, which was subsequently used to transfect mouse bone marrow mesenchymal stem cells (MBMMSCs) and significantly suppressed the development of collagen‐induced arthritis (CIA) in DBA/1j mice. In addition, PD‐L1‐transfected MBMMSCs (PD‐L1‐MBMMSCs) ameliorated joint damage, reduced proinflammatory cytokine expression, and inhibited T and B cell activation. Furthermore, PD‐L1‐MBMMSCs decreased the number of dendritic cells and increased the numbers of regulatory T cells and regulatory B cells in joints of CIA mice. In conclusion, our results provided a potential therapeutic strategy for RA treatment with PD‐L1‐MBMMSC‐targeted therapy.

Background: Metformin is an old drug used for the treatment of type 2 diabetes mellitus and can play a variety of roles by regulating the gut microbiota. The number of research articles on metformin in the gut microbiota has increased annually; however, no bibliometric tools have been used to analyze the research status and hot trends in this field. This study presents a bibliometric analysis of publications on metformin and gut microbiota. Methods: We searched the Web of Science core collection database on June 8, 2023, for papers related to metformin and gut microbiota from 2012 to 2022. We used Microsoft Excel 2021, VOSviewer1.6.19, CiteSpace 6.2.4, and R software package “bibliometrix” 4.0.0 to analyze the countries, institutions, authors, journals, citations, and keywords of the included publications. Results: We included 517 papers, and the trend in publications increased over the last 11 years. The 517 articles were from 57 countries, including 991 institutions and 3316 authors, and were published in 259 journals. China led all countries (233 papers) and the most influential institution was the Chinese Academy of Sciences (16 papers). PLOS ONE (19 papers) was the most popular journal, and Nature (1598 citations) was the most cited journal. Li and Kim were the 2 most published authors (six papers each), and Cani (272 co-citations) was the most co-cited author. “Metabolites,” “aging,” and “intestinal barrier” were emerging topics in this field. Conclusions: This bibliometric study comprehensively summarizes the research trends and progress of metformin and gut microbiota, and provides new research topics and trends for studying the effects of metformin on gut microbiota in different diseases.