Chronic constipation (CC) is a highly prevalent and burdensome gastrointestinal disorder. Accumulating evidence highlights the link between imbalances in the gut microbiome and constipation. However, the mechanisms by which the microbiome and microbial metabolites affect gut movement remain poorly understood. In this review, we discuss recent studies on the alteration in the gut microbiota in patients with CC and the effectiveness of probiotics in treating gut motility disorder. We highlight the mechanisms that explain how the gut microbiome and its metabolism are linked to gut movement and how intestinal microecological interventions may counteract these changes based on the enteric nervous system, the central nervous system, the immune function, and the ability to modify intestinal secretion and the hormonal milieu. In particular, microbiota-based approaches that modulate the levels of short-chain fatty acids and tryptophan catabolites or that target the 5-hydroxytryptamine and Toll-like receptor pathways may hold therapeutic promise. Finally, we discuss the existing limitations of microecological management in treating constipation and suggest feasible directions for future research.

/pdf/crosstalk-between-the-gut-microbiome-and-colonic-motility-in-28jt7kap.pdf

Crosstalk between the Gut Microbiome and Colonic Motility in Chronic Constipation: Potential Mechanisms and Microbiota Modulation

As one of the promising next-generation probiotics (NGPs), Akkermansia muciniphila, a well-known mucin-degrading bacterium, has been proven to be closely related to the metabolic diseases of its human host. However, the role of A. muciniphila in the host's intestinal health remains ambiguous. Here, we comprehensively summarize and discuss the characteristics, the distribution, and the colonization of A. muciniphila in the human gastrointestinal tract (GIT). We propose that the application of A. muciniphila as a biomarker for longevity, for diagnostics and prognostics of intestinal diseases, or for intestinal health should be cautiously considered. Precise dietary regulation can mediate the treatment of intestinal diseases by altering the abundance of A. muciniphila. Although the beneficial role of A. muciniphila and its component in intestinal inflammation has been discovered, in gnotobiotic mice with specific gut microbiota, certain genotype, and colorectal cancer, or in animal models infected with a specific pathogen, A. muciniphila may be related to the occurrence and development of intestinal diseases. Genomic analysis, emphasizing the strain-level phylogenetic differences of A. muciniphila, indicates that a clear description and discussion of each strain is critical before its practical application. Our review provides much needed insight for the precise application of A. muciniphila. 

/pdf/rational-consideration-of-akkermansia-muciniphila-targeting-662sbppo.pdf

Rational consideration of Akkermansia muciniphila targeting intestinal health: advantages and challenges

Dietary synbiotic ameliorates constipation through the modulation of gut microbiota and its metabolic function.

Constipation is the most common gastrointestinal complaint all over the world, and it is a risk factor of colorectal cancer. In this study, the protective of Quercetin against loperamide-induced constipation and its potential mechanism in a rat model were investigated. Results showed that Quercetin at 25 mg/kg and 50 mg/kg could significantly (p < .05) increase the intestinal transit rate, motilin, gastrin, substance P levels, and concentration of short-chain fatty acids (SCFAs), reduce the somatostatin levels, and improve the gastrointestinal peristalsis of rats. In addition, the expression levels of enteric nerve-related factors, glial cell line-derived neurotrophic factor (GDNF), transient receptor potential vanilloid 1 (TRPV1), nitric oxide synthase (NOS), c-Kit, stem cell factor (SCF), and aquaporin 3 (AQP3) were examined by RT-qPCR and/or Western blot analysis. The results suggest that Quercetin relieves loperamide-induced constipation by increasing the levels of interstitial cells of Cajal markers (c-Kit and SCF), as well as AQP3. In conclusion, the present study suggested that Quercetin exerted a protective effect against loperamide-induced constipation, which may be associated with its role in regulation of multiple signal pathways.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/fsn3.2296

The potential of Quercetin to protect against loperamide-induced constipation in rats.

Yellow tea, a rare type tea from China, has a rich breadth of functional ingredients and benefits the gastrointestinal tract. However, it is not clear whether the yellow tea extract can alleviate constipation. Therefore, we used loperamide-induced constipation in mice to evaluate the effects of yellow tea extract. Fifty Kunming mice were randomly divided into five groups: normal, model, low-dose yellow tea extract, low-dose yellow tea extract prevention group, and high-dose yellow tea extract prevention group. Mice were administered yellow tea extract for 5 weeks followed by loperamide-induced constipation for the final 2 weeks. The results showed that yellow tea extract alleviated constipation symptoms by improving the fecal water content, defecation weight, and gastrointestinal transit rate. Yellow tea extract intervention also protected colon tissue, regulated serum neurotransmitters, and decreased the vasoactive intestinal peptide level. Furthermore, qRT-PCR indicated that yellow tea extract regulated genes associated with the constipation state, raised 5-HT3 and 5-HT4 and reduced AQP3 and AQP4 mRNA expression. Moreover, we found that yellow tea extract changed the gut microbiota composition. Community diversity and richness were increased and principal co-ordinate analysis demonstrated that the yellow tea extract prophylaxis groups differed from the model group. Difference analysis indicated that yellow tea extract increased Roseburia, Lachnospiraceae_UCG-006, and Bifidobacterium and decreased norank_f_Clostridiales_vadinBB60_group, unclassified_o_Bacteroidales, and Bacteroides, which are correlated with constipation. Based on these results, we believe that regular yellow tea consumption can effectively alleviate constipation.

The protective effects of yellow tea extract against loperamide-induced constipation in mice

This study determined the ameliorative effects of the novel microorganism, Lactobacillus plantarum CQPC02 (LP-CQPC02), fermented in soybean milk, on loperamide-induced constipation in Kunming mice. High-performance liquid chromatography revealed that LP-CQPC02-fermented soybean milk (LP-CQPC02-FSM) had six types of soybean isoflavones, whereas Lactobacillus bulgaricus-fermented soybean milk (LB-FSM) and unfermented soybean milk (U-FSM) only had five types of soybean isoflavones. LP-CQPC02-FSM also contained more total and active soybean isoflavones than LB-FSM and U-FSM. Results from mouse experiments showed that the defecation factors (quantity, fecal weight and water content, gastrointestinal transit ability, and time to first black stool) in the LP-CQPC02-FSM-treated mice were better than those in the LB-FSM- and U-FSM-treated mice. The serum and small intestinal tissue experiments showed that soybean milk increased the motilin, gastrin, endothelin, acetylcholinesterase, substance P, vasoactive intestinal peptide, and glutathione levels and decreased the somatostatin, myeloperoxidase, nitric oxide, and malondialdehyde levels compared with the constipated mice in the control group. The LP-CQPC02-FSM also showed better effects than those of LB-FSM and U-FSM. Further results showed that LP-CQPC02-FSM upregulated cuprozinc-superoxide dismutase (Cu/Zn-SOD), manganese superoxide dismutase (Mn-SOD), catalase (CAT), c-Kit, stem cell factor (SCF), glial cell-derived neurotrophic factor (GDNF), neuronal nitric oxide synthase (nNOS), endothelial nitric oxide synthase (eNOS), and aquaporin-9 (AQP9) and downregulated the expression levels of transient receptor potential cation channel subfamily V member 1 (TRPV1), inducible nitric oxide synthase (iNOS), and aquaporin-3 (AQP3) in the constipated mice. LP-CQPC02-FSM increased the Bacteroides and Akkermansia abundances and decreased the Firmicutes abundance in the feces of the constipated mice and decreased the Firmicutes/Bacteroides ratio. This study confirmed that LP-CQPC02-FSM partially reversed constipation in mice.

Lactobacillus plantarum CQPC02-Fermented Soybean Milk Improves Loperamide-Induced Constipation in Mice.

A newly found strain, Lactobacillus plantarum CQPC01 (LP-CQPC01), was used for soybean milk fermentation, and its effects against constipation were determined. LP-CQPC01-FSM (LP-CQPC01-fermented soybean milk) was found to have six kinds of soybean isoflavones; the isoflavones of LP-CQPC01-FSM were more than those of Lactobacillus bulgaricus-fermented soybean milk (LB-FSM) and unfermented soybean milk (U-FSM). Animal experiment showed that the MTL, Gas, ET, AchE, SP, VIP, and GSH levels in the constipated mice were increased; however, the SS, MPO, NO, and MDA levels in the constipated mice were reduced by soybean milk treatment. Further, LP-CQPC01-FSM increased the mRNA and protein expression of Cu/Zn-SOD, Mn-SOD, CAT, c-Kit, SCF, and GDNF and reduced the expression of TRPV1 and NOS relative to those of the mice with untreated constipation. LP-CQPC01 could be used as a new starter to produce high-quality soybean milk, which might be used as a functional drink.

https://onlinelibrary.wiley.com/doi/epdf/10.1002/fsn3.1048

Effects of Lactobacillus plantarum CQPC01‐fermented soybean milk on activated carbon‐induced constipation through its antioxidant activity in mice

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Lactobacillus plantarum CQPC02-Fermented Soybean Milk Improves Loperamide-Induced Constipation in Mice.

Effects of Lactobacillus plantarum CQPC01‐fermented soybean milk on activated carbon‐induced constipation through its antioxidant activity in mice