Roles of Gut Microbiota and Metabolites in Pathogenesis of Functional Constipation

Abstract

Functional constipation (FC), a condition characterized by heterogeneous symptoms (infrequent bowel movements, hard stools, excessive straining, or a sense of incomplete evacuation), is prevalent over the world. It is a multifactorial disorder and can be categorized into four subgroups according to different pathological mechanisms: normal transit constipation (NTC), slow transit constipation (STC), defecatory disorders (DD), and mixed type. Recently, growing evidence from human and animals has pointed that there was a strong association between gut microbiota and FC based on the brain-gut-microbiome axis. Studies have reported that the main characteristics of gut microbiota in FC patients were the relative decrease of beneficial bacteria such as Lactobacillus and Bifidobacterium, the relative increase of potential pathogens, and the reduced species richness. Gut microbiota can modulate gut functions through the metabolites of bacterial fermentation, among which short-chain fatty acids (SCFAs), secondary bile salts (BAs), and methane occupied more important positions and could trigger the release of gut hormones from enteroendocrine cells (EECs), such as 5-hydroxytryptamine (5-HT), peptide YY (PYY), and glucagon-like peptide-1 (GLP-1). Subsequently, these gut hormones can influence gut sensation, secretion, and motility, primarily through activating specific receptors distributed on smooth muscle cells, enteric neurons, and epithelial cells. However, research findings were inconsistent and even conflicting, which may be partially due to various confounding factors. Future studies should take the associated confounders into consideration and adopt multiomics research strategies to obtain more complete conclusions and to provide reliable theoretical support for exploring new therapeutic targets.

Neurotransmitter and Intestinal Interactions: Focus on the Microbiota-Gut-Brain Axis in Irritable Bowel Syndrome

“…In IBS patients, the physiological manifestations are closely related to neurotransmitters, including abnormal gastrointestinal motility, visceral sensory abnormalities, central sensory abnormalities, anxiety, and depression ( 68 ). Changes in microbial composition and metabolomics are related to the abnormality in neurotransmitter expression in the system, and would also influence the intestinal neuronal pathways that control intestinal sensorimotor function ( 69 , 70 ) These neurotransmitters not only regulate blood flow, but also influence intestinal movement, the absorption of nutrients, natural immunity of the gastrointestinal system, and the microbiota. Therefore, the pathways and mechanisms that are involved in neurotransmitter synthesis, as well as neuron inactivation, could serve as potential targets for therapeutic drugs for psychiatric and neurological diseases because they play such an important role in brain function.development ( 71 ).…”

Sleep Deficiency Is Associated With Exacerbation of Symptoms and Impairment of Anorectal and Autonomic Functions in Patients With Functional Constipation

“…Notably, the gut microbiota is another potential mechanism that affects the rectal sensitivity in patients with FC. Previous studies reported a decrease in beneficial bacteria such as Lactobacillus, an increase in harmful bacteria, and a reduction in species richness in FC patients (Wang and Yao, 2021). Colonic functions could be modulated by gut microbiota via the metabolites of bacterial fermentation, which could trigger the release of gut hormones.…”

Efficacy of Bacillus coagulans BC01 on loperamide hydrochloride-induced constipation model in Kunming mice

“…Intestinal nerve parameters that promote intestinal motility and the transport of contents are secreted by intestinal neural networks in the gastrointestinal tract ( 31 ). Gastrointestinal hormones are small-molecule peptides, some of which also exist in the central nervous system, so they are also referred to as brain-gut peptides or neurotransmitters ( 32 – 34 ). After binding to receptors on target cells, gastrointestinal hormones play important regulatory roles in the absorption, movement, secretion, and immune health of the digestive system through different signaling mechanisms, some of which are closely related to constipation ( 35 ).…”