Microbially derived polyunsaturated fatty acid as a modulator of gastrointestinal motility

Abstract

Gastrointestinal (GI) motility requires coordination among several cell types in the intestinal epithelium and the neuromuscular apparatus. A disruption in GI motility was primarily attributed to disruption of this coordinated effort among different host cells, but recent studies have begun to uncover how the products of gut microbiota can alter GI motility by modulating the function of different host cells and the interactions among them. In this issue of the JCI, Chen, Qiu, et al. used a reverse translation approach, isolating a Shigella sp. - peristaltic contraction-inhibiting bacterium (PIB) - from a cohort of patients with intractable constipation. They identified an ω-3 polyunsaturated fatty acid (PUFA), docosapentaenoic acid (DPA), produced by this Shigella variant, as an important driver of constipation using a series of microbiologic, biochemical, and genetic manipulations combined with in vitro and in vivo studies. This finding advances the field, given that production of DPA is rare in the human gut and appears to have a distinct effect on GI physiology.

Figure 1. Schematic summary of mechanisms underlying microbial modulation of GI physiology.

The conventional, discovery-to-translation approach of studying microbial modulation of GI transit has focused on the effect of known bacterial metabolites, such as short-chain fatty acids and tryptophan metabolites (–12); cell wall components like LPS; and bacterial functions such as transformation of primary bile acids, on the different cell types (–9, 15, 16). In contrast, the Chen, Qiu, et al. study used a reverse translation approach, starting with patients diagnosed with IFC and identifying the microbial meditator DPA that prolonged GI transit. Similar to other metabolites, DPA likely alters GI transit by an effect on the enteric nervous system (17). SMCs, smooth muscle cells; 5-HT, serotonin; 5-HTR, serotonin receptor; CFTR, cystic fibrosis transmembrane conductance regulator;