Dietary inulin ameliorates obesity-induced severe acute pancreatitis via gut-pancreas axis

Obesity is a definitive factor of severity and mortality of acute pancreatitis (AP), and gut microbiota dysbiosis is involved in its pathogenesis. However, the effect of gut microbiota modulation by dietary components on high fat diet (HFD)-induced severe AP remains unclear. Here, we found that the...

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Main Authors: Xin Li, Pan Zheng, Yaoyu Zou, Langyi Guan, Nianshuang Li, Jianping Liu, Nonghua Lu, Yin Zhu, Cong He
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Gut Microbes
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Online Access:https://www.tandfonline.com/doi/10.1080/19490976.2024.2436949
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author Xin Li
Pan Zheng
Yaoyu Zou
Langyi Guan
Nianshuang Li
Jianping Liu
Nonghua Lu
Yin Zhu
Cong He
author_facet Xin Li
Pan Zheng
Yaoyu Zou
Langyi Guan
Nianshuang Li
Jianping Liu
Nonghua Lu
Yin Zhu
Cong He
author_sort Xin Li
collection DOAJ
description Obesity is a definitive factor of severity and mortality of acute pancreatitis (AP), and gut microbiota dysbiosis is involved in its pathogenesis. However, the effect of gut microbiota modulation by dietary components on high fat diet (HFD)-induced severe AP remains unclear. Here, we found that the inulin, a soluble dietary fiber, mitigated pancreatic injury and systematic inflammation in mice fed HFD, which was dependent on gut microbiota as this protective effect was attenuated in germ-free mice. Inulin treatment suppressed the overgrowth of pathogenic bacteria Escherichia Shigella, Enterococcus, Klebsiella, while increased the abundance of probiotics Akkermansia. Fecal microbiota transplantation from inulin-treated mice to recipient mice reduced pancreatic damage and remodeled intestinal homeostasis. Additionally, inulin increased fecal short chain fatty acids (SCFAs), strengthened gut barrier and restored Paneth cells. The beneficial effect of inulin on improving pancreatic damage and leaky gut was diminished after the suppression of SCFAs. Notably, SCFAs administration, especially butyrate, to HFD mice blocked pancreatic and intestinal injury with the inhibition of histone deacetylase 3 (HDAC3), and pharmacological HDAC3 inhibition mimicked the ameliorative effect of SCFAs. Mechanically, butyrate modulated macrophage M1/M2 polarization balance by suppressing HDAC3 and subsequent acetylation of histone H3K27. Collectively, our data offer new insights into the gut microbiota-pancreas axis that may be leveraged to augment the potential supplementation of prebiotic inulin in the management of obesity associated severe AP.
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spelling doaj-art-e5ebc8b712c948449fe872b21c02408f2025-08-20T02:21:52ZengTaylor & Francis GroupGut Microbes1949-09761949-09842024-12-0116110.1080/19490976.2024.2436949Dietary inulin ameliorates obesity-induced severe acute pancreatitis via gut-pancreas axisXin Li0Pan Zheng1Yaoyu Zou2Langyi Guan3Nianshuang Li4Jianping Liu5Nonghua Lu6Yin Zhu7Cong He8Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, ChinaDepartment of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, ChinaDepartment of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, ChinaDepartment of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, ChinaDepartment of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, ChinaDepartment of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, ChinaDepartment of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, ChinaDepartment of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, ChinaDepartment of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, ChinaObesity is a definitive factor of severity and mortality of acute pancreatitis (AP), and gut microbiota dysbiosis is involved in its pathogenesis. However, the effect of gut microbiota modulation by dietary components on high fat diet (HFD)-induced severe AP remains unclear. Here, we found that the inulin, a soluble dietary fiber, mitigated pancreatic injury and systematic inflammation in mice fed HFD, which was dependent on gut microbiota as this protective effect was attenuated in germ-free mice. Inulin treatment suppressed the overgrowth of pathogenic bacteria Escherichia Shigella, Enterococcus, Klebsiella, while increased the abundance of probiotics Akkermansia. Fecal microbiota transplantation from inulin-treated mice to recipient mice reduced pancreatic damage and remodeled intestinal homeostasis. Additionally, inulin increased fecal short chain fatty acids (SCFAs), strengthened gut barrier and restored Paneth cells. The beneficial effect of inulin on improving pancreatic damage and leaky gut was diminished after the suppression of SCFAs. Notably, SCFAs administration, especially butyrate, to HFD mice blocked pancreatic and intestinal injury with the inhibition of histone deacetylase 3 (HDAC3), and pharmacological HDAC3 inhibition mimicked the ameliorative effect of SCFAs. Mechanically, butyrate modulated macrophage M1/M2 polarization balance by suppressing HDAC3 and subsequent acetylation of histone H3K27. Collectively, our data offer new insights into the gut microbiota-pancreas axis that may be leveraged to augment the potential supplementation of prebiotic inulin in the management of obesity associated severe AP.https://www.tandfonline.com/doi/10.1080/19490976.2024.2436949Acute pancreatitishigh fat dietinulingut microbiotashort chain fatty acids
spellingShingle Xin Li
Pan Zheng
Yaoyu Zou
Langyi Guan
Nianshuang Li
Jianping Liu
Nonghua Lu
Yin Zhu
Cong He
Dietary inulin ameliorates obesity-induced severe acute pancreatitis via gut-pancreas axis
Gut Microbes
Acute pancreatitis
high fat diet
inulin
gut microbiota
short chain fatty acids
title Dietary inulin ameliorates obesity-induced severe acute pancreatitis via gut-pancreas axis
title_full Dietary inulin ameliorates obesity-induced severe acute pancreatitis via gut-pancreas axis
title_fullStr Dietary inulin ameliorates obesity-induced severe acute pancreatitis via gut-pancreas axis
title_full_unstemmed Dietary inulin ameliorates obesity-induced severe acute pancreatitis via gut-pancreas axis
title_short Dietary inulin ameliorates obesity-induced severe acute pancreatitis via gut-pancreas axis
title_sort dietary inulin ameliorates obesity induced severe acute pancreatitis via gut pancreas axis
topic Acute pancreatitis
high fat diet
inulin
gut microbiota
short chain fatty acids
url https://www.tandfonline.com/doi/10.1080/19490976.2024.2436949
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