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通过调节肠道微生物群和短链脂肪酸改善抗结核药物引起的大鼠肠道不良反应。

Improve Anti-Tuberculosis Drugs-Induced Intestinal Adverse Reactions in Rat by Modulating Gut Microbiota and Short-Chain Fatty Acids.

机构信息

Department of Nutrition and Food Hygiene, School of Public Health, Qingdao University, Qingdao 266021, China.

Institute of Nutrition and Health, School of Public Health, Qingdao University, Qingdao 266021, China.

出版信息

Nutrients. 2022 Apr 17;14(8):1668. doi: 10.3390/nu14081668.

DOI:10.3390/nu14081668
PMID:35458230
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9032531/
Abstract

The adverse effects of anti-tuberculosis (TB) drugs in the intestines were related to alteration of the intestinal microbiota. However, there was less information about microbial metabolism on the adverse reactions. This study aimed to explore whether Lactobacillus casei could regulate gut microbiota or short-chain fatty acids (SCFAs) disorders to protect intestinal adverse reactions induced by isoniazid (H) and rifampicin (R). Male Wistar rats were given low and high doses of Lactobacillus casei two hours before daily administration of anti-TB drugs. After 42 days, colon tissue and blood were collected for analysis. The feces at two-week and six-week were collected to analyze the microbial composition and the content of SCFAs in colon contents was determined. Supplementation of Lactobacillus casei increased the proportion of intestinal goblet cells induced by H and R (p < 0.05). In addition, HR also reduced the level of mucin-2 (p < 0.05), and supplementation of Lactobacillus casei restored. After two weeks of HR intervention, a decrease in OTUs, diversity index, the abundance of Bacteroides, Akkermansia, and Blautia, and an increase of the abundance of Lacetospiraceae NK4A136 group and Rumencoccus UCG-005, were observed compared with the control group (p all < 0.05). These indices in Lactobacillus casei intervention groups were similar to the HR group. Six-week intervention resulted in a dramatic reduction of Lacetospiraceae NK4A136 group, butyric acid, valeric acid and hexanoic acid, while an increase of Bacteroides and Blautia (p all < 0.05). Pretreatment with Lactobacillus casei significantly increased the content of hexanoic acid compared with HR group (p < 0.05). Lactobacillus casei might prevent intestinal injury induced by anti-tuberculosis drugs by regulating gut microbiota and SCFAs metabolism.

摘要

抗结核(TB)药物对肠道的不良反应与肠道微生物群的改变有关。然而,关于微生物代谢与不良反应之间的关系,我们了解得还比较少。本研究旨在探索干酪乳杆菌是否可以通过调节肠道菌群或短链脂肪酸(SCFAs)代谢来预防异烟肼(H)和利福平(R)引起的肠道不良反应。雄性 Wistar 大鼠在每天给予抗结核药物前两小时给予低剂量和高剂量的干酪乳杆菌。42 天后,收集结肠组织和血液进行分析。收集粪便进行分析,以确定微生物组成和结肠内容物中 SCFAs 的含量。补充干酪乳杆菌增加了 H 和 R 诱导的肠道杯状细胞的比例(p<0.05)。此外,HR 还降低了粘蛋白-2 的水平(p<0.05),而补充干酪乳杆菌则恢复了这一水平。在 HR 干预两周后,与对照组相比,OTUs、多样性指数、拟杆菌、阿克曼氏菌和布劳特氏菌的丰度降低,Lacetospiraceae NK4A136 组和鲁米努斯球菌 UCG-005 的丰度增加(p 均<0.05)。与 HR 组相比,干酪乳杆菌干预组的这些指数相似。六周的干预导致 Lacetospiraceae NK4A136 组、丁酸、戊酸和己酸显著减少,而拟杆菌和布劳特氏菌增加(p 均<0.05)。与 HR 组相比,干酪乳杆菌预处理显著增加了己酸的含量(p<0.05)。干酪乳杆菌可能通过调节肠道菌群和 SCFAs 代谢来预防抗结核药物引起的肠道损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd2a/9032531/15b98f2d9e71/nutrients-14-01668-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd2a/9032531/f67e29dddf32/nutrients-14-01668-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd2a/9032531/3e539a78a4d4/nutrients-14-01668-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd2a/9032531/6b3332bc0d7d/nutrients-14-01668-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd2a/9032531/b393a81e048e/nutrients-14-01668-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd2a/9032531/caa678b4f2dd/nutrients-14-01668-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd2a/9032531/15b98f2d9e71/nutrients-14-01668-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd2a/9032531/f67e29dddf32/nutrients-14-01668-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd2a/9032531/3e539a78a4d4/nutrients-14-01668-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd2a/9032531/6b3332bc0d7d/nutrients-14-01668-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd2a/9032531/b393a81e048e/nutrients-14-01668-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd2a/9032531/caa678b4f2dd/nutrients-14-01668-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd2a/9032531/15b98f2d9e71/nutrients-14-01668-g006.jpg

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