Bifidobacterium lactis TY-S01 increases the content of SCFAs, such as isobutyrate acid, butyrate acid, acetic acid, valeric acid, and propionic acid, in the feces of the constipated mice (Tang et al.). These SCFAs may inhibit the growth of pathogenic bacteria by reducing the pH in the small intestine, and improve gut motility by increasing colonic smooth muscle contraction, therefore contributing to the amelioration of constipation symptoms (Araújo and Botelho).

The imbalance of intestinal bacteria can cause the release of inflammatory cytokines, thereby damaging the integrity of gut barrier (Yi et al.). The destruction of gut barrier may result in the further invasion of pathogenic bacteria and their toxins, which aggravates intestinal inflammation. The maintenance of gut barrier integrity can inhibit the adherence of pathogens bacteria and their metabolites and facilitate stool passage (Araújo and Botelho). Zhou et al. reported that the nuclear factor (NF)-κB signaling-mediated inflammation in the small intestine of mice with constipation is inhibited by Bacillus coagulans BC01. Bifidobacterium lactis TY-S01 decreases the mRNA expression of colonic inflammatory cytokines in the constipated mice (Tang et al.). Furthermore, the expression levels of gut barrier-associated key genes, including transient receptor potential vanilloid-1, mucin 2, stem cell factor, claudin-1, occludin c-kit, and glial cell line-derived neurotrophic factor are significantly regulated by Bifidobacterium lactis TY-S01 and Lactobacillus plantarum KFY02 (Tang et al. and Yi et al.), indicating that these probiotics have the potential ability to restore the gut barrier.

The content of motilin, 5-hydroxytryptamine, and substance P in the constipated mice is increased by Bifidobacterium lactis TY-S01, and the secretion of these intestinal hormones has a strong correlation with particular species of gut microbiota (Tang et al.). These intestinal hormones can regulate intestinal peristalsis and improve constipation symptoms (Araújo and Botelho and Yi et al.). Besides, Zhou et al. reported that Bacillus coagulans BC01 reduce the production of vasoactive intestinal peptide and somatostatin in the constipated mice, contributing to the slowing down of intestinal transit time and the relief of constipation.

Apart from the regulation of gut microbiota in the constipated mice by probiotics, Zhang et al. examined the regulatory effect of synbiotic consisting of Bifidobacterium lactis BL-99 and fructooligosaccharide (FOS) on the intestinal flora from constipated individuals in vitro. They found that this synbiotic enhances the level of acetic acid, but also changes the structure of intestinal flora, and increases the abundance of beneficial bacteria. However, human and animal studies evaluating the improved effect of synbiotics on constipation are scarce (Araújo and Botelho).

In summary, although the above-mentioned probiotics show a good efficiency in improving the constipation of mice, randomized clinical trials are needed to further confirm their anti-constipation effect. The molecular mechanisms underlying probiotics effect on constipation, including the identification of key metabolites and their mode of action need to be further investigated. In addition, it is necessary to further strengthen the in vivo studies and mechanism of synbiotics on constipation.

JS wrote the whole manuscript. XZ, K-yP, and HS provided some valuable comments. All authors contributed to the article and approved the submitted version.