Altered gut microbiota-host bile acid metabolism in IBS-D patients with liver depression and spleen deficiency pattern

Liqing Du; Zhaozhou Zhang; Lixiang Zhai; Shujun Xu; Wei Yang; Chunhua Huang; Chengyuan Lin; Linda L D Zhong; Zhaoxiang Bian; Ling Zhao

doi:10.1186/s13020-023-00795-9

Altered gut microbiota-host bile acid metabolism in IBS-D patients with liver depression and spleen deficiency pattern

Chin Med. 2023 Jul 19;18(1):87. doi: 10.1186/s13020-023-00795-9.

Authors

Liqing Du^#¹, Zhaozhou Zhang^#¹, Lixiang Zhai², Shujun Xu², Wei Yang², Chunhua Huang², Chengyuan Lin², Linda L D Zhong³, Zhaoxiang Bian^{4

5}, Ling Zhao⁶

Affiliations

¹ School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, China.
² School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, SAR, China.
³ School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.
⁴ School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, SAR, China. bzxiang@hkbu.edu.hk.
⁵ Institute of Brain and Gut Research, Chinese Medicine Clinical Study Center, School of Chinese Medicine, 7 Hong Kong Baptist University Road, Kowloon, Hong Kong, SAR, China. bzxiang@hkbu.edu.hk.
⁶ School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, China. lzhao@shutcm.edu.cn.

^# Contributed equally.

Abstract

Background: Dysregulation of gut microbiota-host bile acid (BA) co-metabolism is a critical pathogenic factor of diarrhea-predominant irritable bowel syndrome (IBS-D). Traditional Chinese Medicine (TCM), instructed by pattern differentiation, is effective in treating IBS-D, in which liver depression and spleen deficiency (LDSD) is the most prevalent pattern. Still, it is unclear the linkage between the LDSD pattern and the BA metabolic phenotype.

Purpose: This study aimed to uncover the biological basis of the LDSD pattern from the BA metabolic perspective.

Methods: Patients with IBS-D completed questionnaires regarding the irritable bowel severity scoring system (IBS-SSS), stool frequency, Stool Bristol scale, and Self-Rating Scales of mental health. Fasting blood and morning feces were collected to analyze the gut metagenome and BA-related indices/metabolites.

Results: IBS-D patients with LDSD had a higher incidence of BA overexcretion (41% vs. 23% non-LDSD) with significant elevations in fecal total BAs and serum BA precursor 7α-hydroxy-4-cholesten-3-one levels. Compared to controls or non-LDSD patients, LDSD patients had a featured fecal BA profile, with higher proportions of deoxycholic acid (DCA), 7-ketodeoxycholic acid, and lithocholic acid. It is consistent with the BA-metabolizing genomic changes in the LDSD gut microbiota characterized by overabundances of 7-dehydroxylating bacteria and BA-inducible genes (baiCD/E/H). The score of bowel symptoms (stool frequency and abdominal pain) showing greater severity in the LDSD pattern were positively correlated with bai-expressing bacterial abundances and fecal DCA levels separately.

Conclusion: We clarified a differed BA metabolic phenotype in IBS patients with LDSD, which closely correlates with the severity of bowel symptoms. It demonstrates that gut microbiota and host co-metabolism of BAs would provide crucial insight into the biology of the LDSD pattern and its internal relationship with IBS progression.

Keywords: Bile acids; Diarrhea-predominant irritable bowel syndrome; Gut microbiota; Liver depression and spleen deficiency; Traditional Chinese Medicine.

Abstract

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