Lactiplantibacillus plantarum-Derived Indole-3-lactic Acid Ameliorates Intestinal Barrier Integrity through the AhR/Nrf2/NF-κB Axis

Abstract

Our previous studies have shown that Lactiplantibacillus plantarum DPUL-S164-derived indole-3-lactic acid (ILA) ameliorates intestinal epithelial cell barrier injury by activating aryl hydrocarbon receptor (AhR) and nuclear factor erythroid 2related factor 2 (Nrf2) signaling pathways and promoting tight junction protein expression. This study further explored the crucial substances of L. plantarum DPUL-S164 in alleviating intestinal barrier damage in mice through a dextran sodium sulfate-induced ulcerative colitis mouse model. Compared to dead L. plantarum DPUL-S164 (D-S164), live L. plantarum DPUL-S164 (S164) and its tryptophan metabolite, ILA, showed an effective ameliorating effect on the intestinal barrier injury of mice treated by antibiotic cocktail and sodium dextran sulfate, suggesting that the crucial substances of L. plantarum DPUL-S164 ameliorating intestinal barrier injury are its extracellular metabolites. Furthermore, S164 and its tryptophan metabolite, ILA, ameliorate intestinal barrier injury and suppress intestinal inflammation by activating the AhR−Nrf2 pathway and inhibiting the nuclear factor kappa-B (NF-κB) pathway. These results suggest that L. plantarum DPUL-S164 ameliorates intestinal epithelial barrier damage in mice, primarily by producing ILA as a ligand to activate the AhR pathway.

Indole-3-Lactic Acid Derived from Lacticaseibacillus paracasei Inhibits Helicobacter pylori Infection via Destruction of Bacteria Cells, Protection of Gastric Mucosa Epithelial Cells, and Alleviation of Inflammation

“…pylori were also down-regulated by ILA. Extensive reports have demonstrated that indole metabolites can effectively mitigate gastrointestinal injury caused by stress, suppress pro-inflammatory pathways, and boost anti-inflammatory pathways. , In the intestine, ILA has been shown to mitigate inflammation in epithelial cells by downregulating IL-8 levels as well as reduce mucosal inflammation in mice by suppressing TNF-α and IL-6 expression . Furthermore, pretreatment with ILA effectively inhibited ultraviolet B (UVB)-induced production of IL-6 in HaCaT human keratinocytes .…”

Characterization of Eurotium cristatum Fermented Thinned Young Apple and Mechanisms Underlying Its Alleviating Impacts on Experimental Colitis

“…Wang et al , reported that Lactobacillus-derived indole lactic acid could promote the expression of key bacterial enzymes implicated in tryptophan metabolism, leading to the synthesis of other indole derivatives including indole-3-propionic acid and indole-3-acetic acid, possessing the ability to reduce colonic inflammation. Anticolitis effect of indole lactic acid was also shown in previous studies conducted by Li et al and Wang et al Moreover, anti-inflammation effect of indole-3-carboxaldehyde has been recently recognized. Indole-3-carboxaldehyde has been shown to alleviate inflammation in the colon, liver, and kidney. , Although mechanisms underlying the benefits of indole derivatives remain exclusive, they may act as key PXR-modulating activators, subsequently attenuating inflammation by inhibiting NF-κB signaling. − …”