Intestinal flora imbalance promotes alcohol‑induced liver fibrosis by the TGFβ/smad signaling pathway in mice

Zhang,Dong; Hao,Xiuxian; Xu,Lili; Cui,Jing; Xue,Li; Tian,Zibin

doi:10.3892/ol.2017.6762

Intestinal flora imbalance promotes alcohol‑induced liver fibrosis by the TGFβ/smad signaling pathway in mice

Authors:
- Dong Zhang
- Xiuxian Hao
- Lili Xu
- Jing Cui
- Li Xue
- Zibin Tian
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Affiliations: Medical College, Qingdao University, Qingdao, Shandong 266042, P.R. China, Department of Endocrinology, Qingdao Center Hospital, Qingdao, Shandong 266042, P.R. China, Department of Endocrinology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China, Department of Emergency, The Third People's Hospital of Qingdao, Qingdao, Shandong 266041, P.R. China, Department of Gastroenterology, Qingdao Center Hospital, Qingdao, Shandong 266042, P.R. China, Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China
Published online on: August 17, 2017 https://doi.org/10.3892/ol.2017.6762
Pages: 4511-4516
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Intestinal flora performs a crucial role in human health and its imbalance may cause numerous pathological changes. The liver can also affect the intestinal function through bile secretion via the enterohepatic cycle. The pathophysiological association between the gut and the liver is described as the gut‑liver axis. The present study investigated the role of intestinal flora in alcohol‑induced liver fibrosis. A total of 36 C57 mice were randomly and equally divided into 3 different dietary regimes: Group I (alcohol injury; received alcohol); group II (alcohol injury with flora imbalance; received alcohol plus lincomycin hydrochloride) and group III (alcohol injury with corrected flora imbalance; received alcohol, lincomycin hydrochloride and extra probiotics). The present study then investigated several indicators of liver damage. Alkaline phosphatase (ALP) levels, aspartate aminotransferase (AST) levels and alanine aminotransferase (ALT) levels in mice serum were studied. Masson staining and Annexin V‑fluorescein isothiocyanate/propidium iodide double staining was also performed, and the expression of mothers against decapentaplegic homolog (smad) 3 and smad4 proteins in hepatic stellate cells (HSCs) of the mice was examined using western blot analysis. The levels of serum ALP, AST and ALT were the highest in group II mice, and all 3 levels decreased in group III mice compared with those from group II. The degree of liver fibrosis was aggravated in group II mice compared with group I mice. The apoptosis of HSCs was significantly inhibited in group II mice, but was increased in group III mice. The HSCs in group II mice exhibited higher expression of smad3 and smad4, whilst group III mice (with corrected intestinal flora imbalance) exhibited downregulated expression of smad3 and smad4. The present data indicates that the intestinal flora perform a significant role in maintaining liver homeostasis. Furthermore, an imbalance of intestinal flora can exacerbate alcohol‑induced liver fibrosis in mice through the transforming growth factor β/SMA/MAD homology signaling pathway, which subsequently leads to more serious liver damage.

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