Gut microbiota-derived short-chain fatty acids protect against the progression of endometriosis.
Gut microbiota-derived short-chain fatty acids protect against the progression of endometriosis.
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肠道微生物群衍生的短链脂肪酸可防止子宫内膜异位症的进展。
DOI：
10.26508/lsa.202101224
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发表时间：
2021-12
影响因子：
4.4
通讯作者：
Kommagani R
中科院分区：
文献类型：
--
作者：
Chadchan SB;Popli P;Ambati CR;Tycksen E;Han SJ;Bulun SE;Putluri N;Biest SW;Kommagani R
这项研究表明，肠源性正丁酸通过激活RAP1GAP GT3的表达来抑制RAP1致癌通路，从而保护子宫内膜异位症，表明正丁酸与肠道微生物群和子宫内膜异位症疾病有关。全世界有1.96亿人患有子宫内膜异位症，这是一种疼痛的疾病，其中子宫内膜组织在腹部腹膜表面植入并增殖。关于子宫内膜异位症的起源理论仍然没有定论。而高达90%的女性经历逆行月经，只有10%的发展子宫内膜异位症，这表明改变腹膜环境的因素可能有助于子宫内膜异位症。在此，我们报告说，虽然一些肠道细菌促进子宫内膜异位症，其他人通过发酵纤维产生短链脂肪酸来防止子宫内膜异位症。具体来说，我们发现改变的肠道微生物群驱动了子宫内膜异位症病变的生长，并且患有子宫内膜异位症的小鼠的粪便比没有子宫内膜异位症的小鼠的粪便含有更少的短链脂肪酸和正丁酸盐。在临床前小鼠模型中，用正丁酸盐治疗可减少小鼠肿瘤病变和人肿瘤病变的生长。机制研究表明，正丁酸盐通过G蛋白偶联受体、组蛋白脱乙酰酶和GT3激活蛋白RAP1GAP抑制人卵巢癌细胞存活和病变生长。我们的研究结果将使未来的研究，旨在开发诊断测试，肠道细菌代谢产物和治疗策略，膳食补充剂，正丁酸类似物，或益生菌子宫内膜异位症。
This study revealed that gut-derived n-butyrate protects against endometriosis by activating the expression of RAP1GAP GTPase to inhibit the RAP1 oncogenic pathway, indicating n-butyrate is linked with intestinal microbiota and endometriosis disease. Worldwide, ∼196 million are afflicted with endometriosis, a painful disease in which endometrial tissue implants and proliferates on abdominal peritoneal surfaces. Theories on the origin of endometriosis remained inconclusive. Whereas up to 90% of women experience retrograde menstruation, only 10% develop endometriosis, suggesting that factors that alter peritoneal environment might contribute to endometriosis. Herein, we report that whereas some gut bacteria promote endometriosis, others protect against endometriosis by fermenting fiber to produce short-chain fatty acids. Specifically, we found that altered gut microbiota drives endometriotic lesion growth and feces from mice with endometriosis contained less of short-chain fatty acid and n-butyrate than feces from mice without endometriosis. Treatment with n-butyrate reduced growth of both mouse endometriotic lesions and human endometriotic lesions in a pre-clinical mouse model. Mechanistic studies revealed that n-butyrate inhibited human endometriotic cell survival and lesion growth through G-protein–coupled receptors, histone deacetylases, and a GTPase activating protein, RAP1GAP. Our findings will enable future studies aimed at developing diagnostic tests, gut bacteria metabolites and treatment strategies, dietary supplements, n-butyrate analogs, or probiotics for endometriosis.
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DOI：
10.4049/jimmunol.1701625
发表时间：
2018-04-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Bhatt B;Zeng P;Zhu H;Sivaprakasam S;Li S;Xiao H;Dong L;Shiao P;Kolhe R;Patel N;Li H;Levy-Bercowski D;Ganapathy V;Singh N
通讯作者：
Singh N
影响因子：
7.7
作者：
den Besten, Gijs;Bleeker, Aycha;Bakker, Barbara M.
通讯作者：
Bakker, Barbara M.
影响因子：
7.3
作者：
Ang Z;Ding JL
通讯作者：
Ding JL
DOI：
10.1152/ajpheart.00515.2019
发表时间：
2021-03-01
影响因子：
4.8
作者：
Castro, Pollyana Ribeiro;Fernandes Bittencourt, Lucas Felipe;Barcelos, Luciola Silva
通讯作者：
Barcelos, Luciola Silva
影响因子：
11.2
作者：
Bailey CL;Kelly P;Casey PJ
通讯作者：
Casey PJ