Limosilactobacillus reuteri SXDT-32-derived shikimic acid protects against colonic inflammation in piglets by inhibiting the PI3K-Akt pathway

Abstract Background Colitis caused by bacterial infection is a major global health challenge. Unfortunately, current treatment options are limited. We previously disclosed that L. reuteri SXDT-32 was enriched in the feces of an ancient diarrhea-resistant pig breed (Mashen pig) in China over 2500 yea...

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Main Authors: Ying Chen, Chengzeng Luo, Zhaohan Zhan, Shuo Liu, Chunran Teng, Ruixiao Mao, Shunfen Zhang, Xunbozan Zhang, Qingshi Meng, Ruqing Zhong, Liang Chen, Hongfu Zhang
Format: Article
Language:English
Published: BMC 2025-06-01
Series:Journal of Animal Science and Biotechnology
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Online Access:https://doi.org/10.1186/s40104-025-01221-w
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author Ying Chen
Chengzeng Luo
Zhaohan Zhan
Shuo Liu
Chunran Teng
Ruixiao Mao
Shunfen Zhang
Xunbozan Zhang
Qingshi Meng
Ruqing Zhong
Liang Chen
Hongfu Zhang
author_facet Ying Chen
Chengzeng Luo
Zhaohan Zhan
Shuo Liu
Chunran Teng
Ruixiao Mao
Shunfen Zhang
Xunbozan Zhang
Qingshi Meng
Ruqing Zhong
Liang Chen
Hongfu Zhang
author_sort Ying Chen
collection DOAJ
description Abstract Background Colitis caused by bacterial infection is a major global health challenge. Unfortunately, current treatment options are limited. We previously disclosed that L. reuteri SXDT-32 was enriched in the feces of an ancient diarrhea-resistant pig breed (Mashen pig) in China over 2500 years old. As diarrhea is often closely associated with intestinal inflammation, L. reuteri SXDT-32 was identified as a potential beneficial bacterium to prevent intestinal inflammation. However, the precise mechanisms involved remained unclear. Results Our tests showed that L. reuteri SXDT-32 alleviated colonic damage induced by pathogenic E. coli SKLAN202302 in weaned pigs by enhancing barrier integrity and inhibiting inflammation. The transcriptomics revealed that L. reuteri SXDT-32 protected against inflammatory injury by inhibiting the PI3K-AKT signaling pathway. Metabolite analysis indicated that the content of shikimic acid (SA) was substantially elevated in the colonic mucosa of L. reuteri SXDT-32-fed piglets (P < 0.05). In addition, Liquid Chromatography-Mass Spectrometer (LC-MS) analysis showed significant increases in SA content in both the colonic chyme of L. reuteri SXDT-32-fed piglets and the supernatant of in vitro grown cultures of L. reuteri SXDT-32 (P < 0.05). Polymerase chain reaction (PCR) analysis identified gene aroE from L. reuteri SXDT-32, which is a key gene directly linked to SA synthesis, and elevated shikimate dehydrogenase (SD, encoded by aroE) was also detected in both L. reuteri SXDT-32 and the colonic mucosa of piglets fed L. reuteri SXDT-32 (P < 0.01). In vitro Caco-2 cell experiments demonstrated that SA, L. reuteri SXDT-32, and the supernatant from in vitro grown cultures of L. reuteri SXDT-32 exhibited comparable inhibitory effects on the PI3K-Akt pathway to those of the PI3K inhibitor LY294002. Conclusions L. reuteri SXDT-32 alleviated intestinal inflammation in piglets by producing SA that inhibits the PI3K-Akt pathway. This study provides an innovative approach for the treatment and prevention of colitis caused by bacterial infection.
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spelling doaj-art-3484d5a00e9f4698be5bfc6fc39c579a2025-08-20T02:39:48ZengBMCJournal of Animal Science and Biotechnology2049-18912025-06-0116111510.1186/s40104-025-01221-wLimosilactobacillus reuteri SXDT-32-derived shikimic acid protects against colonic inflammation in piglets by inhibiting the PI3K-Akt pathwayYing Chen0Chengzeng Luo1Zhaohan Zhan2Shuo Liu3Chunran Teng4Ruixiao Mao5Shunfen Zhang6Xunbozan Zhang7Qingshi Meng8Ruqing Zhong9Liang Chen10Hongfu Zhang11State Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Sciences, Chinese Academy of Agricultural SciencesState Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Sciences, Chinese Academy of Agricultural SciencesState Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Sciences, Chinese Academy of Agricultural SciencesState Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Sciences, Chinese Academy of Agricultural SciencesState Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Sciences, Chinese Academy of Agricultural SciencesState Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Sciences, Chinese Academy of Agricultural SciencesState Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Sciences, Chinese Academy of Agricultural SciencesState Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Sciences, Chinese Academy of Agricultural SciencesState Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Sciences, Chinese Academy of Agricultural SciencesState Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Sciences, Chinese Academy of Agricultural SciencesState Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Sciences, Chinese Academy of Agricultural SciencesState Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Sciences, Chinese Academy of Agricultural SciencesAbstract Background Colitis caused by bacterial infection is a major global health challenge. Unfortunately, current treatment options are limited. We previously disclosed that L. reuteri SXDT-32 was enriched in the feces of an ancient diarrhea-resistant pig breed (Mashen pig) in China over 2500 years old. As diarrhea is often closely associated with intestinal inflammation, L. reuteri SXDT-32 was identified as a potential beneficial bacterium to prevent intestinal inflammation. However, the precise mechanisms involved remained unclear. Results Our tests showed that L. reuteri SXDT-32 alleviated colonic damage induced by pathogenic E. coli SKLAN202302 in weaned pigs by enhancing barrier integrity and inhibiting inflammation. The transcriptomics revealed that L. reuteri SXDT-32 protected against inflammatory injury by inhibiting the PI3K-AKT signaling pathway. Metabolite analysis indicated that the content of shikimic acid (SA) was substantially elevated in the colonic mucosa of L. reuteri SXDT-32-fed piglets (P < 0.05). In addition, Liquid Chromatography-Mass Spectrometer (LC-MS) analysis showed significant increases in SA content in both the colonic chyme of L. reuteri SXDT-32-fed piglets and the supernatant of in vitro grown cultures of L. reuteri SXDT-32 (P < 0.05). Polymerase chain reaction (PCR) analysis identified gene aroE from L. reuteri SXDT-32, which is a key gene directly linked to SA synthesis, and elevated shikimate dehydrogenase (SD, encoded by aroE) was also detected in both L. reuteri SXDT-32 and the colonic mucosa of piglets fed L. reuteri SXDT-32 (P < 0.01). In vitro Caco-2 cell experiments demonstrated that SA, L. reuteri SXDT-32, and the supernatant from in vitro grown cultures of L. reuteri SXDT-32 exhibited comparable inhibitory effects on the PI3K-Akt pathway to those of the PI3K inhibitor LY294002. Conclusions L. reuteri SXDT-32 alleviated intestinal inflammation in piglets by producing SA that inhibits the PI3K-Akt pathway. This study provides an innovative approach for the treatment and prevention of colitis caused by bacterial infection.https://doi.org/10.1186/s40104-025-01221-wIntestinal inflammationL. reuteri SXDT-32PI3K-Akt pathwayShikimic acid
spellingShingle Ying Chen
Chengzeng Luo
Zhaohan Zhan
Shuo Liu
Chunran Teng
Ruixiao Mao
Shunfen Zhang
Xunbozan Zhang
Qingshi Meng
Ruqing Zhong
Liang Chen
Hongfu Zhang
Limosilactobacillus reuteri SXDT-32-derived shikimic acid protects against colonic inflammation in piglets by inhibiting the PI3K-Akt pathway
Journal of Animal Science and Biotechnology
Intestinal inflammation
L. reuteri SXDT-32
PI3K-Akt pathway
Shikimic acid
title Limosilactobacillus reuteri SXDT-32-derived shikimic acid protects against colonic inflammation in piglets by inhibiting the PI3K-Akt pathway
title_full Limosilactobacillus reuteri SXDT-32-derived shikimic acid protects against colonic inflammation in piglets by inhibiting the PI3K-Akt pathway
title_fullStr Limosilactobacillus reuteri SXDT-32-derived shikimic acid protects against colonic inflammation in piglets by inhibiting the PI3K-Akt pathway
title_full_unstemmed Limosilactobacillus reuteri SXDT-32-derived shikimic acid protects against colonic inflammation in piglets by inhibiting the PI3K-Akt pathway
title_short Limosilactobacillus reuteri SXDT-32-derived shikimic acid protects against colonic inflammation in piglets by inhibiting the PI3K-Akt pathway
title_sort limosilactobacillus reuteri sxdt 32 derived shikimic acid protects against colonic inflammation in piglets by inhibiting the pi3k akt pathway
topic Intestinal inflammation
L. reuteri SXDT-32
PI3K-Akt pathway
Shikimic acid
url https://doi.org/10.1186/s40104-025-01221-w
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