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.

Indole acetic acid (IAA), an intestinal bacteria-derived tryptophan metabolite, has been detected at abnormal concentrations in the cerebrospinal fluid and urine of depressed individuals. The effects of such altered IAA concentrations on mood regulation are not known. A mouse model of unpredictable chronic mild stress (UCMS) was used to assess the effects of IAA administration (50 mg/kg). Treatment with IAA for 5 weeks attenuated depression and anxiety-like behaviours, improved hypothalamus–pituitary–adrenal axis dysfunction and increased brain-derived neurotrophic factor expression. IAA supplementation also enhanced the serotonin pathway in the brain and gut. UCMS caused an imbalance of microbial indole metabolites in the colon, whereas IAA treatment reversed this. However, IAA intake did not affect the concentrations of indoles in the brain. Intestinal bacteria in different sections of the gut were altered by IAA treatment, with the colon showing more changes than other segments. The gut microbiome in the colon had increased proportions of Ruminococcaceae UCG013, Ruminiclostridium 6, Prevotella, Alloprevotella and Bacteroides species, which can produce short-chain fatty acids and indole derivatives. Cumulatively, our study highlights the potential of IAA treatment to alleviate mood disorders and offers a theoretical basis for understanding the antidepressant effects of IAA.

Intestinal peristalsis is vital for gastrointestinal physiology and host homeostasis and is frequently dysregulated in intestinal disorders. Gut microbiota can regulate gut motility, especially through the tryptophan metabolism pathway. However, the role of indoles as microbial tryptophan metabolites in colonic function requires further exploration. Here, we show that the delivery of indole acetic acid (IAA) targeting the colon can improve gut motility by activating the aryl hydrocarbon receptor (AHR). To achieve colon-targeted delivery, Eudragit S-100 (ES) and chitosan (CS) were used as drug carriers. After optimisation, IAA-loaded ES-coated CS nanoparticles exhibited an encapsulation efficiency of 83% and a drug-loading capacity of 16%. These nanoparticles exhibited pH-dependent characteristics and remained stable in acidic conditions and the upper intestine. In simulated intestinal fluid (pH 7.4) and colonic lumen, considerable amounts of IAA were released after approximately 4 h. Compared with free IAA, the nanoparticles exerted enhanced therapeutic effects on gut movement disorders induced by loperamide. The efficacy of IAA treatment was attributable to the activation of the AHR signalling pathway and increased levels of AHR agonists. Furthermore, the oral administration of IAA-loaded nanoparticles promoted serotonin secretion and maintained the intestinal barrier function. The experimental outcomes demonstrate the efficiency of the proposed colon-specific delivery system and highlight the role of IAA, produced by gut microbiota metabolism, in regulating gut peristalsis through AHR activation.

Immunoglobulin A (IgA), as the most secreted immunoglobulin in the intestine, plays an irreplaceable role in mucosal immunity regulation. Previous studies have indicated that Lactobacillus showed strain specificity in stimulating the secretion of IgA through intestinal mucosal lymphocytes. The reason for this phenomenon is not clear. The current studies have been aimed at exploring the effect of a strain on the secretion of IgA in the host’s intestine, but the mechanism behind it has not been seriously studied. Based on this, we selected five strains of Lactobacillus fermentum isolated from different individuals to determine whether there are intraspecific differences in stimulating the secretion of IgA from the intestinal mucosa. It was found that IgA concentrations in different intestinal segments and faeces induced by L. fermentum were different. 12-1 and X6L1 strains increased the secretion of IgA by the intestine significantly. In addition, different strains of L. fermentum were also proven to have different effects on the host gut microbiota but no significant effects on IgA-coated microbiota. Besides, it was speculated that different strains of L. fermentum may act on different pathways to stimulate IgA in a non-inflammatory manner. By explaining the differences of IgA secretion in the host’s intestine tract stimulated by different strains of L. fermentum, it is expected to provide a theoretical basis for the stimulation of intestinal secretion of IgA by Lactobacillus and a new direction for exploring the relationship between Lactobacillus and human immunity.

Normal pregnancy involves numerous physiological changes, including changes in hormone levels, immune responses, and metabolism. Although several studies have shown that the gut microbiota may have an important role in the progression of pregnancy, these findings have been inconsistent, and the relationship between the gut microbiota and metabolites that change dynamically during and after pregnancy remains to be clarified. In this longitudinal study, we comprehensively profiled the temporal dynamics of the gut microbiota, Bifidobacterium communities, and serum and faecal metabolomes of 31 women during their pregnancies and postpartum periods. The microbial composition changed as gestation progressed, with the pregnancy and postpartum periods exhibiting distinct bacterial community characteristics, including significant alterations in the genera of the Lachnospiraceae or Ruminococcaceae families, especially the Lachnospiraceae FCS020 group and Ruminococcaceae UCG-003. Metabolic dynamics, characterised by changes in nutrients important for fetal growth (e.g., docosatrienoic acid), anti-inflammatory metabolites (e.g., trans-3-indoleacrylic acid), and steroid hormones (e.g., progesterone), were observed in both serum and faecal samples during pregnancy. Moreover, a complex correlation was identified between the pregnancy-related microbiota and metabolites, with Ruminococcus1 and Ruminococcaceae UCG-013 making important contributions to changes in faecal and serum metabolites, respectively. Overall, a highly coordinated microbiota–metabolite regulatory network may underlie the pregnancy process. These findings provide a foundation for enhancing our understanding of the molecular processes occurring during the progression of pregnancy, thereby contributing to nutrition and health management during this period.

Eicosapentaenoic acid (EPA) and Bifidobacterium breve strains have individually shown beneficial effects in neurodevelopmental disorders, but their combinatorial effects remain unclear. This study investigated whether B. breve strains metabolize EPA in vitro and explored their potential relevance to autism spectrum disorder (ASD). Five B. breve strains were co-fermented with EPA. BB1 and BB2, but not other strains, exhibited EPA-metabolizing capabilities. Both strains promoted DHA production and enriched arachidonic acid (AA), while EPA concurrently altered their lipid profiles. Notably, BB1 specifically increased eicosadienoic acid (EDA) levels, whereas BB2 promoted oleic acid (OA) secretion. Network pharmacology predicted potential molecular targets of these metabolites previously implicated in ASD. Strain-specific targets were associated with EDA and OA, respectively, with EPA targets largely overlapping those of both strains. PPI and KEGG analyses revealed core molecular hubs, and molecular docking predicted metabolite-receptor interactions. For BB1 + EPA, metabolites were predicted to bind to AKT1, MTOR, PIK3CA, ESR1, and PPARG, targeting PI3K-Akt-mTOR and AMPK pathways. For BB2 + EPA, binding to ESR1, MAPK3, and PPARG targeted the AMPK pathway. Collectively, B. breve BB1 and BB2 exhibit strain-specific EPA-metabolizing capabilities, producing distinct bioactive metabolites that are computationally predicted to interact with ASD-related pathways, providing testable hypotheses for future ASD‑related mechanistic studies.