Mechanisms of Action of Probiotics and the Gastrointestinal Microbiota on Gut Motility and Constipation

Abstract

Constipation is a common and burdensome gastrointestinal disorder that may result from altered gastrointestinal motility. The effect of probiotics on constipation has been increasingly investigated in both animal and human studies, showing promising results. However, there is still uncertainty regarding the mechanisms of action of probiotics on gut motility and constipation. Several factors are vital to normal gut motility, including immune and nervous system function, bile acid metabolism and mucus secretion, and the gastrointestinal microbiota and fermentation; an imbalance or dysfunction in any of these components may contribute to aberrant gut motility and, consequently, symptoms of constipation. For example, adults with functional constipation have significantly decreased numbers of bifidobacteria (with one study showing a mean difference of 1 log₁₀/g) and lactobacilli (mean difference, 1.4 log₁₀/g) in stool samples, as well as higher breath methane, compared with control subjects. Modifying the gut luminal environment with certain probiotic strains may affect motility and secretion in the gut and, hence, provide a benefit for patients with constipation. Therefore, this review explores the mechanisms through which probiotics may exert an effect on gut motility and constipation. Nevertheless, the majority of current evidence is derived from animal studies, and therefore, further human studies are needed to determine the mechanisms through specific probiotic strains that might be effective in constipation.

Keywords: constipation; gastrointestinal microbiome; gut motility; mechanisms; probiotics.

FIGURE 1

Factors that control gut motility. The gut luminal environment (including the gastrointestinal microbiota and fermentation), immune system, enteric nervous system, and central nervous system are highly interrelated and control gut motility; disturbance in any of these overlapping systems may contribute to symptoms of constipation.

FIGURE 2

Interrelated factors involved in the pathophysiology of constipation as potential targets for the therapeutic role of probiotics. Probiotics affect the gastrointestinal microbiota composition, the byproducts of which interact with pattern-recognition receptors, such as TLRs, as well as with dendritic cells. SCFAs increase intestinal regulatory T cells, which limit intestinal inflammation, by reducing histone deacetylase 9 gene expression (53). The gastrointestinal microbiota regulates 5-HT production by elevating its synthesis by host enterochromaffin cells via the release of metabolites, such as deoxycholate, which activates TGR5, expressed by enterochromaffin cells (54). 5-HT is also released from enterochromaffin cells in response to SCFAs produced by the gastrointestinal microbiota and stimulates 5-HT3 receptors located on the vagal afferent fibers, resulting in muscle contractions (47). Gases produced by the gastrointestinal microbiota seem to affect gut motility via the ENS, rather than the brain-gut axis; however, the exact mechanisms are still unknown (50). Moreover, the gastrointestinal microbiota is key to the development of the ENS, which is the primary regulator of gut motility, and certain bacteria are known to produce 5-HT. Calcitonin gene–related protein, a sensory neuropeptide, modulates dendritic cell function and may signal the presence of gastrointestinal microbiota to the brain (55). Components of the gastrointestinal microbiota also act via intestinal dendritic cells to influence the inflammatory process (56). TLRs signaling controls ENS structure and neuromuscular function and hence motility (57). Bile acids activate TGR5 expressed by enterochromaffin cells and myenteric neurons and release 5-HT and calcitonin genre–related peptide. Furthermore, probiotics appear to interact with the gut-brain axis via the modulation of afferent sensory nerves that influence gut motility. CH₄, methane; ENS, enteric nervous system; H_2, hydrogen; TGR5, a G protein–coupled receptor; TLR, toll-like receptor; 5-HT, 5-hydroxytryptamine; 5-HT3, 5-hydroxytryptamine type 3.