An excess of fecal bile acids (BAs) is thought to be one of the mechanisms for diarrhea-predominant irritable bowel syndrome (IBS-D). However, the factors causing excessive BA excretion remain incompletely studied. Given the importance of gut microbiota in BA metabolism, we hypothesized that gut dysbiosis might contribute to excessive BA excretion in IBS-D. By performing BA-related metabolic and metagenomic analyses in 290 IBS-D patients and 89 healthy volunteers, we found that 24.5% of IBS-D patients exhibited excessive excretion of total BAs and alteration of BA-transforming bacteria in feces. Notably, the increase in Clostridia bacteria (e.g., C. scindens) was positively associated with the levels of fecal BAs and serum 7α-hydroxy-4-cholesten-3-one (C4), but negatively correlated with serum fibroblast growth factor 19 (FGF19) concentration. Furthermore, colonization with Clostridia-rich IBS-D fecal microbiota or C. scindens individually enhanced serum C4 and hepatic conjugated BAs but reduced ileal FGF19 expression in mice. Inhibition of Clostridium species with vancomycin yielded opposite results. Clostridia-derived BAs suppressed the intestinal FGF19 expression in vitro and in vivo. In conclusion, this study demonstrates that the Clostridia-rich microbiota contributes to excessive BA excretion in IBS-D patients, which provides a mechanistic hypothesis with testable clinical implications.

Diabetic cardiomyopathy (DCM) is a cardiovascular disease which has been reported as a major cause of mortality worldwide for several years. Berberine (BBR) is a natural compound extracted from a Chinese herb, with a clinically reported anti‑DCM effect; however, its molecular mechanisms have not yet been fully elucidated. The present study indicated that BBR markedly alleviated DCM by inhibiting IL‑1β secretion and the expression of gasdermin D (Gsdmd) at the post‑transcriptional level. Considering the importance of microRNAs (miRNAs/miRs) in the regulation of the post‑transcriptional process of specific genes, the ability of BBR to upregulate the expression levels of miR‑18a‑3p by activating its promoter (‑1,000/‑500) was examined. Notably, miR‑18a‑3p targeted Gsdmd and abated pyroptosis in high glucose‑treated H9C2 cells. Moreover, miR‑18a‑3p overexpression inhibited Gsdmd expression and improved biomarkers of cardiac function in a rat model of DCM. On the whole, the findings of the present study indicate that BBR alleviates DCM by inhibiting miR‑18a‑3p‑mediated Gsdmd activation; thus, BBR may be considered a potential therapeutic agent for the treatment of DCM.

Three of the most lethal cancers in the world are the gastrointestinal cancers—gastric (GC), esophageal (EC) and colorectal cancer (CRC)—which are ranked as third, sixth and fourth in cancer deaths globally. Early detection of these cancers is difficult, and a quest is currently on to find non-invasive screening tests to detect these cancers. The reprogramming of energy metabolism is a hallmark of cancer, notably, an increased dependence on aerobic glycolysis which is often referred to as the Warburg effect. This metabolic change results in a unique metabolic profile that distinguishes cancer cells from normal cells. Serum metabolomics analyses allow one to measure the end products of both host and microbiota metabolism present at the time of sample collection. It is a non-invasive procedure requiring only blood collection which encourages greater patient compliance to have more frequent screenings for cancer. In the following review we will examine some of the most current serum metabolomics studies in order to compare their results and test a hypothesis that different tumors, notably, from EC, GC and CRC, have distinguishing serum metabolite profiles.

Hepatic fibrosis is the main pathological basis for chronic cirrhosis, and activated hepatic stellate cells (HSCs) are the primary cells involved in liver fibrosis. Our study analyzed anti-fibrosis long noncoding RNAs (lncRNAs) in activated human HSCs (hHSCs). We performed RNA sequencing (RNA-seq) and bioinformatics analysis to determine whether lncRNA expression profile changes between hHSCs activation and quiescence. Eight differentially expressed (DE) lncRNAs and three pairs of co-expression lncRNAs-mRNAs were verified by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). A total of 34146 DE lncRNAs were identified in this study. Via gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, we found several DE lncRNAs regulated hHSC activation by participating in DNA bending/packaging complex, growth factor binding and the Hippo signaling pathway (p < 0.05). With lncRNA–mRNA co-expression analysis, three lncRNAs were identified to be associated with connective tissue growth factor (CTGF), fibroblast growth factor 2 (FGF2) and netrin-4 (NTN4). The quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) results of the eight DE lncRNAs and three pairs of co-expression lncRNAs–mRNAs were consistent with the RNA-seq data and previous reports. Several lncRNAs may serve as potential targets to reverse the progression of liver fibrosis. This study provides a first insight into lncRNA expression profile changes associated with activated human HSCs.

Cardiac hypertrophy, worldwide known as an adaptive functional compensatory state of myocardial stress, is mainly believed to proceed to severe heart diseases, even to sudden death. Emerging studies have explored the microRNA alteration during hypertrophy. However, the mechanisms of microRNAs involved in cardiac hypertrophy are still uncertain. We studied young rats to establish abdominal aorta coarctation (AAC) for 4 weeks. With the significant downregulated cardiac function and upregulated hypertrophic biomarkers, AAC‐induced rats showed enlarged myocardiocytes and alterations in microRNAs, especially downregulated miR‐31‐5p. miR‐31‐5p targets the 3′UTR of Nfatc2ip and inhibits myocardial hypertrophy in vitro and in vivo. Furthermore, we verified that Nfatc2ip is necessary and sufficient for cardiac hypertrophy in neonatal rat cardiomyocytes. Moreover, we found miR‐31‐5p inhibited the colocalization of Nfatc2ip and hypertrophic gene β‐Mhc. Luciferase assay and ChiP‐qPCR test demonstrated that Nfatc2ip binded to the core‐promoter of β‐Mhc and enhanced its transcriptional activity. Above all, our study found a new pathway, mir‐31‐5p/Nfatc2ip/β‐Mhc, which is involved in cardiac hypertrophy, suggesting a potential target for intervention of cardiac hypertrophy.