Lactobacillus-derived indole-3-lactic acid ameliorates colitis in cesarean-born offspring via activation of aryl hydrocarbon receptor

Yanan Xia; Chang Liu; Ruijia Li; Mengqi Zheng; Bingcheng Feng; Jiahui Gao; Xin Long; Lixiang Li; Shiyang Li; Xiuli Zuo; Yanqing Li

doi:10.1016/j.isci.2023.108279

Lactobacillus-derived indole-3-lactic acid ameliorates colitis in cesarean-born offspring via activation of aryl hydrocarbon receptor

iScience. 2023 Oct 19;26(11):108279. doi: 10.1016/j.isci.2023.108279. eCollection 2023 Nov 17.

Authors

Yanan Xia^{1

2}, Chang Liu^{1

2}, Ruijia Li^{1

2}, Mengqi Zheng^{1

2}, Bingcheng Feng³, Jiahui Gao^{1

2}, Xin Long^{1

2}, Lixiang Li^{1

2

4}, Shiyang Li^{1

5}, Xiuli Zuo^{1

2

4

6}, Yanqing Li^{1

2

4}

Affiliations

¹ Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, China.
² Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, China.
³ Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
⁴ Shandong Provincial Clinical Research Center for Digestive Disease, Qilu Hospital of Shandong University, Jinan, Shandong, China.
⁵ Advanced Medical Research Institute, Shandong University, Jinan, China.
⁶ Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital of Shandong University, Jinan, Shandong, China.

Abstract

Cesarean section (CS) delivery is known to disrupt the transmission of maternal microbiota to offspring, leading to an increased risk of inflammatory bowel disease (IBD). However, the underlying mechanisms remain poorly characterized. Here, we demonstrate that CS birth renders mice susceptible to dextran sulfate sodium (DSS)-induced colitis and impairs group 3 innate lymphoid cell (ILC3) development. Additionally, CS induces a sustained decrease in Lactobacillus abundance, which subsequently contributes to the colitis progression and ILC3 deficiency. Supplementation with a probiotic strain, L. acidophilus, or its metabolite, indole-3-lactic acid (ILA), can attenuate intestinal inflammation and restore ILC3 frequency and interleukin (IL)-22 level in CS offspring. Mechanistically, we indicate that ILA activates ILC3 through the aryl hydrocarbon receptor (AhR) signaling. Overall, our findings uncover a detrimental role of CS-induced gut dysbiosis in the pathogenesis of colitis and suggest L. acidophilus and ILA as potential targets to re-establish intestinal homeostasis in CS offspring.

Keywords: Biological sciences; Immunology; Microbiology; Physiology.