Whether myogenesis is affected by the maternal gut dysbacteriosis still remains ambiguous. In this study, first we show the elevated level of lipopolysaccharides (LPS) in a gut microbiota dysbiosis mouse model. Second, we demonstrate that the diameter of muscle fibers, limb development, and somitogenesis were inhibited in both the gut microbiota dysbiosis and LPS exposed mice and chicken embryos. These might be due to LPS disturbed the cell survival and key genes which regulate the somitogenesis and myogenesis. RNA sequencing and subsequent validation experiments verified that retinoic acid (RA) signaling perturbation was mainly responsible for the aberrant somite formation and differentiation. Subsequently, we found that LPS‐induced reactive oxygen species (ROS generation and antioxidant genes such as Nrf2, AKR1B10) contributed to the above ‐mentioned interference with RA signaling. These findings highlight that the gut microbiota homeostasis is also involved in regulating the development of muscle progenitor cells during pregnancy.

Growing evidence suggests an adverse impact of gut microbiota dysbiosis on human health. However, it remains unclear whether embryonic osteogenesis is affected by maternal gut dysbacteriosis. In this study, we observed that elevated lipopolysaccharide (LPS) levels led to skeletal developmental retardation in an established mouse model of gut microbiota dysbiosis. Using chick embryos exposed to dysbacteriosis-derived LPS, we found restriction in the development of long bones as demonstrated by Alcian blue and alizarin red staining. Micro-CT and histological analysis exhibited decreased trabecular volume, bone mineral density, and collagen production, as well as suppressed osteoblastic gene expression (Ocn, Runx2, Osx, and Dlx5) in chick embryonic phalanges following LPS treatment. Atomic force microscopy manifested decreased roughness of MC3T3-E1 cells and poorly developed matrix vesicles (MVs) in presence of LPS. The expression of the aforementioned osteoblastic genes was suppressed in MC3T3-E1 cells as well. High-throughput RNA sequencing indicated that retinoic acid (RA) may play an important role in LPS-induced osteopenia. The addition of RA suppressed Dlx5 expression in MC3T3-E1 cells, as was also seen when exposed to LPS. Quantitative PCR, Western blot, and immunofluorescent staining showed that retinoic acid receptor α (RARα) was upregulated by LPS or RA treatment, while the expression of DLX5 was downregulated. CYP1B1 expression was increased by LPS treatment in MC3T3-E1 cells, which might be attributed to the increased inflammatory factors and subsequently activated NF-κB signaling. Eventually, blocking RA signals with AGN193109 successfully restored LPS-inhibited osteoblastic gene expression. Taken together, our data reveals that maternal gut microbiota dysbiosis can interfere with bone ossification, in which Dlx5 expression regulated by RA signaling plays an important role.

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The interindividual heterogeneity in response to the antihypertensive effect of irbesartan has received considerable attention because of gene polymorphism. In this study, we investigated the new combinational influences of AGTR1 and ABCB1 gene polymorphism on the therapeutic effect of irbesartan among Chinese hypertensive patients. A total of 353 samples including 168 normal people and 185 hypertensive patients were adopted, and genotypes comprise ABCB1 (CC, CT, and TT) and AGTR1 (AA and AC) in this study. The results of multiple linear regression models showed that no statistically significant differences were observed in blood pressure change following irbesartan administration in each genotype from either ABCB1 (CC, CT, and TT) or AGTR1 (AA and AC). However, spline smoothing analysis demonstrated that the blood pressure therapeutic responses of irbesartan presented a noticeable difference among different ABCB1 genotypes when irbesartan doses reached over 300 ng/mL. Eventually, we assumed that the different drug responses of irbesartan among various AGTR1 genotypes were due to the diversity of the irbesartan-conjugated protein, which is responsible for crossing-coupled intracellular G-protein-coupled receptors (GPCRs).