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Ketogenic Diet Exacerbates L-Arginine-Induced Acute Pancreatitis and Reveals the Therapeutic Potential of Butyrate

The ketogenic diet (KD) has emerged as a popular weight-loss regimen in recent years. However, it has been confirmed to elicit a mild inflammatory response in the intestinal epithelium and exacerbate various digestive disorders. The severity of acute pancreatitis (AP) is closely associated with the...

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Autores principales: Xia, He, Guo, Jing, Shen, Jian, Jiang, Shiman, Han, Shengyi, Li, Lanjuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10609823/
https://www.ncbi.nlm.nih.gov/pubmed/37892502
http://dx.doi.org/10.3390/nu15204427
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author Xia, He
Guo, Jing
Shen, Jian
Jiang, Shiman
Han, Shengyi
Li, Lanjuan
author_facet Xia, He
Guo, Jing
Shen, Jian
Jiang, Shiman
Han, Shengyi
Li, Lanjuan
author_sort Xia, He
collection PubMed
description The ketogenic diet (KD) has emerged as a popular weight-loss regimen in recent years. However, it has been confirmed to elicit a mild inflammatory response in the intestinal epithelium and exacerbate various digestive disorders. The severity of acute pancreatitis (AP) is closely associated with the permeability of the intestinal epithelium and gut microbiota, yet the impact of KD on acute pancreatitis remains unclear. In this study, we induced acute pancreatitis using L-arginine in mice fed with KD. The consumption of KD resulted in an elevation of lipopolysaccharide-binding protein (LBP), accompanied by upregulated cytokines (IL-1a, IL-5, IL-12, MIP-1a, and Rantes) and dysfunction of the intestinal barrier both in control and AP groups. The bloom of Lachnospirales and Erysipelotrichales was observed as a specific profile of gut microbiota in KD-fed mice with AP, along with downregulation of carbohydrate metabolism and depletion of short-chain fatty acids (SCFAs). Antibiotic decontamination reduced the cytokine storm and tissue necrosis but did not significantly improve the integrity of the intestinal barrier in KD-fed mice with AP. The overgrowth of Mycoplasmatales in feces and Enterobacterales in colonic tissue appears to explain the limitation of antibiotic treatment to aggravate acute pancreatitis. Butyrate supplementation attenuated the depletion of SCFAs, promoted the intestinal barrier, and reduced the necrotic area in AP mice. The bloom of Bacteroidales and the correlated increase in tryptophan metabolism explain the therapeutic potential of butyrate supplements for acute pancreatitis. In conclusion, our findings suggest that the ketogenic diet exacerbates acute pancreatitis through its impact on the gut microbiota and subsequent disruption of the intestinal barrier, while butyrate supplementation reverses this effect.
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spelling pubmed-106098232023-10-28 Ketogenic Diet Exacerbates L-Arginine-Induced Acute Pancreatitis and Reveals the Therapeutic Potential of Butyrate Xia, He Guo, Jing Shen, Jian Jiang, Shiman Han, Shengyi Li, Lanjuan Nutrients Article The ketogenic diet (KD) has emerged as a popular weight-loss regimen in recent years. However, it has been confirmed to elicit a mild inflammatory response in the intestinal epithelium and exacerbate various digestive disorders. The severity of acute pancreatitis (AP) is closely associated with the permeability of the intestinal epithelium and gut microbiota, yet the impact of KD on acute pancreatitis remains unclear. In this study, we induced acute pancreatitis using L-arginine in mice fed with KD. The consumption of KD resulted in an elevation of lipopolysaccharide-binding protein (LBP), accompanied by upregulated cytokines (IL-1a, IL-5, IL-12, MIP-1a, and Rantes) and dysfunction of the intestinal barrier both in control and AP groups. The bloom of Lachnospirales and Erysipelotrichales was observed as a specific profile of gut microbiota in KD-fed mice with AP, along with downregulation of carbohydrate metabolism and depletion of short-chain fatty acids (SCFAs). Antibiotic decontamination reduced the cytokine storm and tissue necrosis but did not significantly improve the integrity of the intestinal barrier in KD-fed mice with AP. The overgrowth of Mycoplasmatales in feces and Enterobacterales in colonic tissue appears to explain the limitation of antibiotic treatment to aggravate acute pancreatitis. Butyrate supplementation attenuated the depletion of SCFAs, promoted the intestinal barrier, and reduced the necrotic area in AP mice. The bloom of Bacteroidales and the correlated increase in tryptophan metabolism explain the therapeutic potential of butyrate supplements for acute pancreatitis. In conclusion, our findings suggest that the ketogenic diet exacerbates acute pancreatitis through its impact on the gut microbiota and subsequent disruption of the intestinal barrier, while butyrate supplementation reverses this effect. MDPI 2023-10-18 /pmc/articles/PMC10609823/ /pubmed/37892502 http://dx.doi.org/10.3390/nu15204427 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Xia, He
Guo, Jing
Shen, Jian
Jiang, Shiman
Han, Shengyi
Li, Lanjuan
Ketogenic Diet Exacerbates L-Arginine-Induced Acute Pancreatitis and Reveals the Therapeutic Potential of Butyrate
title Ketogenic Diet Exacerbates L-Arginine-Induced Acute Pancreatitis and Reveals the Therapeutic Potential of Butyrate
title_full Ketogenic Diet Exacerbates L-Arginine-Induced Acute Pancreatitis and Reveals the Therapeutic Potential of Butyrate
title_fullStr Ketogenic Diet Exacerbates L-Arginine-Induced Acute Pancreatitis and Reveals the Therapeutic Potential of Butyrate
title_full_unstemmed Ketogenic Diet Exacerbates L-Arginine-Induced Acute Pancreatitis and Reveals the Therapeutic Potential of Butyrate
title_short Ketogenic Diet Exacerbates L-Arginine-Induced Acute Pancreatitis and Reveals the Therapeutic Potential of Butyrate
title_sort ketogenic diet exacerbates l-arginine-induced acute pancreatitis and reveals the therapeutic potential of butyrate
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10609823/
https://www.ncbi.nlm.nih.gov/pubmed/37892502
http://dx.doi.org/10.3390/nu15204427
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