Phytochemical-induced mucin accumulation in the gastrointestinal lumen is independent of the microbiota

Abstract

The mucus layer is critical to gastrointestinal health and ecology. Dietary phytochemicals are well documented to stimulate mucus production and secretion, but the underlying mechanism and effects on gut health are poorly understood. We fed germ-free and conventional mice diets containing approximately 0.4% of polyphenols per gram to determine if the phytochemical-induced accumulation of mucin in the gastrointestinal lumen is dependent on the microbiota. In addition, we assess how increased mucin shapes microbial communities in conventional mice. Germ-free mice receiving a pea ( Pisum sativuum ) seed coat proanthocyanidin-containing diet (PA) had greater levels of fecal mucin compared to the non-proanthocyanidin-containing (NPA) pea seed coat diet control ( P < 0.05), confirming that fecal mucin accumulation is independent of the gut microbiota. Conventional mice fed the PA diet and a red osier dogwood (ROD; Cornus sericea ) extract diet (DW) had higher mucin levels compared to a control diet without phytochemicals ( P < 0.01 and P < 0.05, respectively). The increase in luminal mucin was associated with consistent increases in bacterial taxa belonging to Lachnospiraceae and [ Clostridium ] leptum species and a decrease in Romboutsia species. We conclude that phytochemicals have the ability to alter gut microbial ecology by increasing the amount of mucin in the gastrointestinal lumen.

Impact of grape polyphenols on <i>Akkermansia muciniphila</i> and the gut barrier

“…Other studies have indicated that dietary polyphenol supplementation increased fecal mucus [73] , [74] ; however, in these studies, measurements of mucus layer thickness were not performed, and it was not determined whether polyphenols induced mucus production or a redistribution of mucus into the fecal pellet. The polyphenol EGCG, which is abundant in green tea, was found to aggregate salivary mucins and reduce mucin networking due to its protein-precipitating properties [75] .…”

“…Supplementing germ-free or conventional mice with PAC-rich pea seed coat extract increased fecal mucin levels [74] , suggesting that PACs directly increase mucus production rather than suppressing the production via alterations to gut bacteria. Additionally, mucin genes ( Muc1–4 ) were counterintuitively expressed at higher levels in germ-free mice when compared to conventional mice [84] ; however, it is not known how the fecal mucin level or mucus layer thickness was affected.…”

Polyphenols as Drivers of a Homeostatic Gut Microecology and Immuno-Metabolic Traits of Akkermansia muciniphila: From Mouse to Man

“…Hence, the accumulation of non-glycosylated Muc2 precursors weakens the protective mucus layer and exacerbates the adhesion and mucus degradation by opportunistic pathogens, in addition to reducing mucosa-associated symbionts, such as A. muciniphila [24,25]. These gut ecological disturbances were reported to notably reduce the A. muciniphila population but were shown to be prevented and restored by the consumption of polyphenols [26,27].…”

“…On the one hand, phenolics and derivatives can act as antimicrobials, inhibiting opportunistic bacteria that are abundant in metabolic diseases [28]. On the other hand, polyphenols and phenolic metabolites can simultaneously act locally in the intestinal mucosa, be absorbed through the epithelium into the systemic circulation, and regulate anti-inflammatory markers [27][28][29][30]. In line with this, the activation of the aryl hydrocarbon receptor (AhR) and the induction of interleukin (IL)-22 appear to be involved in the mechanisms of action, leading to a protective O-glycan-rich mucus layer and reduced mucosal inflammation by polyphenols [47][48][49].…”

“…Recent studies indicate that polyphenols induce goblet cell (GC) differentiation, increase mucus layer thickness, and reduce colitis. However, it remains unclear whether this is a direct effect or whether A. muciniphila is involved [26,27,51].…”