2. Academic Validation
  3. Maternal Western diet mediates susceptibility of offspring to Crohn's-like colitis by deoxycholate generation

Maternal Western diet mediates susceptibility of offspring to Crohn's-like colitis by deoxycholate generation

  • Microbiome. 2023 May 2;11(1):96. doi: 10.1186/s40168-023-01546-6.
Chongyang Huang # 1 2,  Huishi Tan # 3,  Mengyao Song # 1,  Ke Liu # 1,  Hongbin Liu 1,  Jun Wang 2,  Yanqiang Shi 4,  Fengyi Hou 1,  Qian Zhou 1,  Ruo Huang 1,  Binghai Shen 1,  Xinlong Lin 1,  Xiaoming Qin 1,  Fachao Zhi 5
Affiliations

Affiliations

  • 1 Guangdong Provincial Key Laboratory of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • 2 Department of Gastroenterology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
  • 3 State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • 4 Institute of Dermatology and Venereology, Dermatology Hospital, Southern Medical University, Guangzhou, China.
  • 5 Guangdong Provincial Key Laboratory of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China. [email protected].
  • # Contributed equally.
PMID: 37131223 DOI: 10.1186/s40168-023-01546-6
Abstract

Background: The Western dietary pattern, characterized by high consumption of fats and sugars, has been strongly associated with an increased risk of developing Crohn's disease (CD). However, the potential impact of maternal obesity or prenatal exposure to a Western diet on offspring's susceptibility to CD remains unclear. Herein, we investigated the effects and underlying mechanisms of a maternal high-fat/high-sugar Western-style diet (WD) on offspring's susceptibility to 2,4,6-Trinitrobenzenesulfonic acid (TNBS)-induced Crohn's-like colitis.

Methods: Maternal dams were fed either a WD or a normal control diet (ND) for eight weeks prior to mating and continued throughout gestation and lactation. Post-weaning, the offspring were subjected to WD and ND to create four groups: ND-born offspring fed a normal diet (N-N) or Western diet (N-W), and WD-born offspring fed a normal (W-N) or Western diet (W-W). At eight weeks of age, they were administered TNBS to induce a CD model.

Results: Our findings revealed that the W-N group exhibited more severe intestinal inflammation than the N-N group, as demonstrated by a lower survival rate, increased weight loss, and a shorter colon length. The W-N group displayed a significant increase in Bacteroidetes, which was accompanied by an accumulation of deoxycholic acid (DCA). Further experimentation confirmed an increased generation of DCA in mice colonized with gut microbes from the W-N group. Moreover, DCA administration aggravated TNBS-induced colitis by promoting Gasdermin D (GSDMD)-mediated Pyroptosis and IL-1beta (IL-1β) production in macrophages. Importantly, the deletion of GSDMD effectively restrains the effect of DCA on TNBS-induced colitis.

Conclusions: Our study demonstrates that a maternal Western-style diet can alter gut microbiota composition and bile acid metabolism in mouse offspring, leading to an increased susceptibility to CD-like colitis. These findings highlight the importance of understanding the long-term consequences of maternal diet on offspring health and may have implications for the prevention and management of Crohn's disease. Video Abstract.

Keywords

Deoxycholic acid; Gasdermin D; Gut microbiota; Intestinal inflammation; Maternal factors; Western diet.

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