Lactose-Induced Chronic Diarrhea Results From Abnormal Luminal Microbial Fermentation and Disorder of Ion Transport in the Colon
Lactose-Induced Chronic Diarrhea Results From Abnormal Luminal Microbial Fermentation and Disorder of Ion Transport in the Colon
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DOI：
10.3389/fphys.2020.00877
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发表时间：
2020-07
影响因子：
4
通讯作者：
H. Xue;Min Zhang;Jinxin Ma;Ting Chen;Fengyun Wang;Xudong Tang
中科院分区：
文献类型：
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作者：
H. Xue;Min Zhang;Jinxin Ma;Ting Chen;Fengyun Wang;Xudong Tang
腹泻是乳糖不耐受受试者的主要腹部症状之一。乳糖引起的腹泻中大肠管腔环境的变化和上皮离子转运障碍尚不清楚。本研究旨在研究增量高乳糖饮食（IHLD，30%/40%/50%）对肠腔微生物群、微生物群衍生代谢物浓度和结肠离子转运的影响。通过16S rRNA扩增子测序分析肠道微生物群，通过气相色谱分析SCFAs浓度，通过检测试剂盒分析半乳糖、乳糖和乳酸；使用室来检测基础离子传输和受激离子传输；通过蛋白质印迹和免疫染色分析结肠粘膜中 SCFA 转运蛋白、Na-H 交换蛋白 3（NHE3）、囊性纤维化转运蛋白调节蛋白（CFTR）和 NKCC1 的表达和位置。盲肠内容物中乳糖、半乳糖和乳酸浓度显着升高（P < 0.01），SCFA浓度显着降低（P < 0.01）。这与毛螺菌科 NK4A136 群和瘤胃球菌科 UCG-005 的消耗以及盲肠微生物群中乳杆菌、埃希氏菌和巨胞菌的相对丰度增加有关。 IHLD组结肠粘膜中单羧酸转运蛋白1的表达降低。 IHLD 组结肠粘膜中 NHE3 表达和磷酸化水平较低，以及去除顶端 Na+ 后 Delta 基础短路电流降低，导致 Na+ 在管腔内积聚，并减少刺激的 Cl- 分泌，同时 CFTR 和 NKCC1 表达低，可补偿腹泻过程中水和电解质的损失。这些结果表明，腹泻状态的持续是通过异常的结肠微生物群发酵维持的，导致管腔内乳糖、半乳糖和乳酸浓度高，SCFA 浓度低，并且 NHE3 表达和磷酸化水平低，Na + 吸收减少。
Diarrhea is one of the major abdominal symptoms in lactose-intolerant subjects. The changes in the large intestinal luminal environment and disorder of the epithelial ion transport in lactose-induced diarrhea remain unclear. The present study aimed to investigate the effect of an incremental high-lactose diet (IHLD, 30%/40%/50%) on luminal microbiota, microbiota-derived metabolite concentrations and colonic ion transport. Gut microbiota were analyzed by 16S rRNA amplicon sequencing and the concentration of SCFAs by gas chromatography, galactose, lactose and lactic acid through assay kit; Ussing chamber was performed to detect basal and stimulated ion transport; The expression and location of SCFA transporters, the Na-H exchanger 3(NHE3), cystic fibrosis transporter regulater (CFTR) and NKCC1 in the colon mucosa were analyzed by western and immunostaining. The concentrations of lactose, galactose and lactic acid of the cecal content were markedly increased (P < 0.01) and SCFA concentration was significantly decreased (P < 0.01). This was associated with depletion of the Lachnospiraceae NK4A136 group and Ruminococcaceae UCG-005 and increased relative abundance of Lactobacillus, escherichia-shigella and megamonas in the cecal microbiota. The expression of monocarboxylate transporter 1 was decreased in the colonic mucosa of the IHLD group. Low NHE3 expression and phosphorylation levels, and decreases in delta basal short circuit current after apical Na+ removal in the colonic mucosa of the IHLD group contributed to Na+ accumulation in the lumen and decrease stimulated Cl– secretion with low CFTR and NKCC1 expression would compensate for water and electrolyte loss during the diarrhea process. These results indicated that the persistence of the diarrhea state was maintained by abnormal colonic microbiota fermentation leading to high concentrations of lactose, galactose and lactic acid and low SCFAs in the lumen, and decreased Na+ absorption with the low NHE3 expression and phosphorylation levels.