Introduction: Koumiss is a fermented horse milk food containing abundant probiotics. Lactobacillus paracasei is a bacterial strain isolated from koumiss that helps regulate the intestinal microbiota. One of the major cause of diarrhea is an imbalance of the intestinal flora. The aim of this study was to investigate whether Lactobacillus paracasei can ameliorate E. coli-induced diarrhea and modulate the gut microbiota.Methods: Mouse models of diarrhea were established via intragastric E. coli O₈ administration. We then attempted to prevent or treat diarrhea in the mice via intragastric administration of a 3 × 10⁸ CFU/mL L. paracasei cell suspension. The severity of diarrhea was evaluated based on the body weight, diarrhea rate, and index, fecal diameter, ileum injury, hematoxylin-eosin (H&E) staining, and diamine oxidase (DAO) and zonulin expression. Expression of the tight junction (TJ) proteins claudin-1, occludin, and zona occludens (ZO-)1 were detected by immunohistochemistry (IHC). Gastrointestinal mRNA expression levels of interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α were detected by real-time polymerase chain reaction (RT-PCR). The microbial composition was analyzed by 16s rRNA sequencing.Results: The L. paracasei demonstrated excellent therapeutic efficacy against diarrhea. It elevated the TJ protein levels and downregulated proinflammatory cytokines IL-6, IL-1β, TNF-α, and p65, myosin light chain 2 (MLC2), myosin light chain kinase (MLCK). Moreover L. paracasei increased those bacteria, which can product short-chain fatty acid (SCFA) such Alistipes, Odoribacter, Roseburia, and Oscillibacter.Conclusion: L. paracasei ameliorated diarrhea by inhibiting activation of the nuclear factor kappa B (NF-κB)-MLCK pathway and increasing the abundance of gut microbiota that produce SCFA.

We evaluated the effects of probiotic compounds on the composition of the gut microbiota. Forty newborn calves were random allocated to the lactic acid bacteria + yeast group (LS group), lactic acid bacteria group (L group), yeast group (S group), and control group (D group). Probiotics containing Lactococcus lactis subsp. lactis, Pediococcus pentosaceus, Lactobacillus plantarum, Saccharomyces cerevisiae, and Kluyveromyces marxianus were fed to calves in the three treatment groups for 15 days. The feeding process lasted 15 days. Fecal samples were collected from all calves at the end of the trial and analyzed using high-throughput 16S rRNA sequencing. Totals of 1,029,260 high-quality reads and 420,010,128 bp of sequences were obtained. Among the four groups, the alpha diversity of gut microbes was significantly higher in newborn cattle in the LS group than in those in the L, S, and D groups. Overall, the dominant phyla were Firmicutes, Actinobacteria, and Bacteroidetes, whereas Bifidobacterium was the most abundant phylum in the gut of cattle in the LS group. Newborn calves from the compound probiotic groups had closely clustered gut bacterial communities and had lower rates of diarrhea. Overall, compound probiotics regulated the intestinal microbiota community structure of newborn calves and improved intestinal health. New information relevant to the prevention of diarrhea is provided by our research in newborn calves.

The hedgehog (HH) signaling pathway is central to the regulation of bone development and homeostasis. HH signaling is not only involved in osteoblast differentiation from bone marrow mesenchymal stem cells (BM-MSCs), but also acts upstream within osteoblasts via the OPG/RANK/RANKL axis to control the expression of RANKL. HH signaling has been found to up-regulate parathyroid hormone related protein (PTHrP) expression in osteoblasts, which in turn activates its downstream targets nuclear factor of activated T cells (NFAT) and cAMP responsive element binding protein (CREB), and as a result CREB and NFAT cooperatively increase RANKL expression and osteoclastogenesis. Osteoblasts must remain in balance with osteoclasts in order to avoid excessive bone formation or resorption, thereby maintaining bone homeostasis. This review systemically summarizes the mechanisms whereby HH signaling induces osteoblast development and controls RANKL expression through PTHrP in osteoblasts. Proper targeting of HH signaling may offer a therapeutic option for treating bone homeostasis disorders.