Hiroshi Fukui1, Reiner Wiest2. 1. Department of Gastroenterology, Endocrinology and Metabolism, Nara Medical University, Kashihara, Japan. 2. Department of Gastroenterology, University Hospital of Visceral Surgery and Medicine, Bern, Switzerland.
Abstract
BACKGROUND: Understanding of the gut-liver axis is important for the up-to-date management of liver cirrhosis, and changes of intestinal functions form the core of this interesting research field. SUMMARY: Most investigators noted small intestinal dysmotility in their patients with liver cirrhosis. Marked changes in the contraction pattern were observed in early manometric studies. The orocecal transit time, particularly small intestinal transit, has generally been reported to be prolonged, which has been demonstrated in multiple investigations to be related to the severity of the liver disease (e.g., Child-Pugh class), the presence of small intestinal bacterial overgrowth (SIBO) and hepatic encephalopathy (HE) as well as a history of spontaneous bacterial peritonitis. Bacteriologically proven SIBO in proximal jejunal aspiration has been reported to be present in up to 59% of cirrhotic patients and is associated with systemic endotoxemia. Clinical and experimental studies suggest that delayed small bowel transit in liver cirrhosis may lead to SIBO, which could contribute to the symptoms of abdominal pain and diarrhea. In addition to autonomic neuropathy, metabolic derangements and diabetic state, SIBO itself may delay intestinal transit in cirrhotic patients. Several studies, both from the West and the East, have shown that the gut microbiota is altered in cirrhotic patients and particularly those with HE. Further, a quantitative change in Bacteroides/Firmicutes ratio, with a prevalence of potentially pathogenic bacteria (e.g., Enterobacteriaceae) and reduction in specific commensals (e.g., Lachnospiraceae), has been described. Structural and functional changes in the intestinal mucosa that contribute to increases in intestinal permeability for bacteria and their products have been observed in patients with liver cirrhosis, which is considered as an important pathogenetic factor for several complications. The mechanism of intestinal barrier dysfunction in cirrhosis is multifactorial, including alcohol, portal hypertension (vascular congestion and dysregulation), endotoxemia, SIBO, local inflammation and, most likely, immunological factors and medications. KEY MESSAGES: This review summarizes major achievements regarding intestinal dysfunction in cirrhosis for future gastroenterology research. The question of whether this intestinal barrier dysfunction is accompanied and/or at least partly caused by structural and functional changes in the epithelial tight junction proteins is as yet unsolved. Development of new strategies to modulate gut-liver interaction is urgently needed.
BACKGROUND: Understanding of the gut-liver axis is important for the up-to-date management of liver cirrhosis, and changes of intestinal functions form the core of this interesting research field. SUMMARY: Most investigators noted small intestinal dysmotility in their patients with liver cirrhosis. Marked changes in the contraction pattern were observed in early manometric studies. The orocecal transit time, particularly small intestinal transit, has generally been reported to be prolonged, which has been demonstrated in multiple investigations to be related to the severity of the liver disease (e.g., Child-Pugh class), the presence of small intestinal bacterial overgrowth (SIBO) and hepatic encephalopathy (HE) as well as a history of spontaneous bacterial peritonitis. Bacteriologically proven SIBO in proximal jejunal aspiration has been reported to be present in up to 59% of cirrhotic patients and is associated with systemic endotoxemia. Clinical and experimental studies suggest that delayed small bowel transit in liver cirrhosis may lead to SIBO, which could contribute to the symptoms of abdominal pain and diarrhea. In addition to autonomic neuropathy, metabolic derangements and diabetic state, SIBO itself may delay intestinal transit in cirrhotic patients. Several studies, both from the West and the East, have shown that the gut microbiota is altered in cirrhotic patients and particularly those with HE. Further, a quantitative change in Bacteroides/Firmicutes ratio, with a prevalence of potentially pathogenic bacteria (e.g., Enterobacteriaceae) and reduction in specific commensals (e.g., Lachnospiraceae), has been described. Structural and functional changes in the intestinal mucosa that contribute to increases in intestinal permeability for bacteria and their products have been observed in patients with liver cirrhosis, which is considered as an important pathogenetic factor for several complications. The mechanism of intestinal barrier dysfunction in cirrhosis is multifactorial, including alcohol, portal hypertension (vascular congestion and dysregulation), endotoxemia, SIBO, local inflammation and, most likely, immunological factors and medications. KEY MESSAGES: This review summarizes major achievements regarding intestinal dysfunction in cirrhosis for future gastroenterology research. The question of whether this intestinal barrier dysfunction is accompanied and/or at least partly caused by structural and functional changes in the epithelial tight junction proteins is as yet unsolved. Development of new strategies to modulate gut-liver interaction is urgently needed.
Entities:
Keywords:
Bacterial translocation; Endotoxemia; Intestinal hyperpermeability; Liver cirrhosis; Small intestinal bacterial overgrowth; Small intestinal dysmotility
Authors: Ulrich Thalheimer; Fosca De Iorio; Franco Capra; Maria del Mar Lleo; Valeria Zuliani; Valentina Ghidini; Maria Carla Tafi; Greta Caburlotto; Micol Gennari; Andrew K Burroughs; Italo Vantini Journal: Eur J Gastroenterol Hepatol Date: 2010-10 Impact factor: 2.566
Authors: Sonia Pascual; José Such; Angel Esteban; Pedro Zapater; Juan A Casellas; José R Aparicio; Eva Girona; Ana Gutiérrez; Fernando Carnices; Jose M Palazón; Javier Sola-Vera; Miguel Pérez-Mateo Journal: Hepatogastroenterology Date: 2003 Sep-Oct
Authors: Bruno Sangro; Stephen L Chan; Tim Meyer; María Reig; Anthony El-Khoueiry; Peter R Galle Journal: J Hepatol Date: 2020-02 Impact factor: 25.083
Authors: Katharine Margaret Irvine; Isanka Ratnasekera; Elizabeth E Powell; David Arthur Hume Journal: Front Immunol Date: 2019-02-25 Impact factor: 7.561
Authors: Luise Ehlers; Karen Bannert; Sarah Rohde; Peggy Berlin; Johannes Reiner; Mats Wiese; Julia Doller; Markus M Lerch; Ali A Aghdassi; Fatuma Meyer; Luzia Valentini; Ottavia Agrifoglio; Cornelia C Metges; Georg Lamprecht; Robert Jaster Journal: J Cell Mol Med Date: 2020-07-06 Impact factor: 5.310
Authors: Fatuma Meyer; Karen Bannert; Mats Wiese; Susanne Esau; Lea F Sautter; Luise Ehlers; Ali A Aghdassi; Cornelia C Metges; Leif-A Garbe; Robert Jaster; Markus M Lerch; Georg Lamprecht; Luzia Valentini Journal: Int J Mol Sci Date: 2020-07-28 Impact factor: 5.923