Gut microbiota profile on women with functional constipation. Human gut microbiome with functional constipation

Introduction Functional constipation is caused by various factors, including luminal factors mediated by microbiota dysbiosis. The gut microbiota plays a fundamental role in several aspects of host health and disease. In this study, we aimed to uncover the effect of supplementation with an indigenous Lactiplantibacillus (formerly Lactobacillus) plantarum IS-10506 probiotic isolated from dadih on the composition and diversity of microbiota and the profile of short-chain fatty acids (SCFAs) in women with functional constipation compared with that in women without constipation. Methods A randomized, double-blind, placebo-controlled clinical trial was conducted on 37 women with functional constipation in Jakarta, Indonesia. The effect of the supplementation of 120 mL fermented milk containing the probiotic strain L. plantarum IS-10506 (1.2 × 1010 CFU/day) on the gut microbiota and SCFA profiles was compared with placebo and 10 non-constipation subjects, by using next-generation sequencing and gas chromatography–mass spectrometry, respectively. Results Baseline data showed dysbiosis of microbiota composition in terms of the Firmicutes/Bacteroidetes ratio and within the Clostridiales order; Ruminococcaceae and Mogibacteriaceae families; and Coprococcus, Prevotella, and Blautia genera. Women with constipation also had lower concentrations for acetate, propionate, and butyrate SCFAs compared with those without constipation. After 21 days of probiotic supplementation, a significant increase in Lactobacillacea abundance showed strong correlation with a significant increase in that of Lachnospiraceae, which in turn balanced the abundance of Ruminococcaceae sp., including Roseburia sp., and of Bilophila sp. The eubiotic tendency of the relative abundance of Roseburia sp. strongly correlated with the increasing SCFA concentration. SCFAs can also interact on the other side of the digestive tract, such as in the enteric nervous system, by stimulating motility to reliave functional constipation. Conclusion The supplementation of fermented milk containing L. plantarum IS-10506 (1.2 × 1010 CFU/day) of dadih origin improved the balance of microbiota toward eubiosis and increased SCFA concentration as underlying molecular mechanisms of relieving functional constipation symptoms in women. Key words: Probiotic, Lactiplantibacillus plantarum IS-10506, functional constipation in women, microbiota profile, SCFA Running title: Microbiota profile in functional constipation

引言 功能性便秘（functional constipation）由多种因素诱发，其中包括由菌群失调（microbiota dysbiosis）介导的管腔因素。肠道菌群在宿主健康与疾病的诸多维度中均发挥着基础性作用。本研究旨在探究从达迪（dadih）中分离得到的本土植物乳杆菌（Lactiplantibacillus plantarum，旧称乳酸杆菌属Lactobacillus）IS-10506益生菌补充剂，对比分析其对功能性便秘女性与非便秘女性的肠道菌群组成、多样性以及短链脂肪酸（short-chain fatty acids, SCFAs）谱的影响。
方法 本研究在印度尼西亚雅加达开展了一项针对37名功能性便秘女性的随机双盲安慰剂对照临床试验。分别采用下一代测序技术与气相色谱-质谱联用法，对比每日补充120mL含植物乳杆菌IS-10506（L. plantarum IS-10506，剂量为1.2×10¹⁰ CFU/天）的发酵乳与安慰剂，以及10名非便秘受试者的肠道菌群与短链脂肪酸谱变化。
结果 基线数据显示，便秘受试者的菌群组成存在失调，具体表现为厚壁菌门/拟杆菌门（Firmicutes/Bacteroidetes）比值异常，梭菌目（Clostridiales）下的瘤胃球菌科（Ruminococcaceae）和摩氏杆菌科（Mogibacteriaceae），以及粪球菌属（Coprococcus）、普雷沃氏菌属（Prevotella）和布劳特氏菌属（Blautia）的相对丰度均出现异常。与非便秘女性相比，便秘女性的乙酸、丙酸和丁酸等短链脂肪酸浓度均显著更低。在接受21天益生菌补充干预后，乳杆菌科（Lactobacillaceae）的丰度显著升高，这与毛螺菌科（Lachnospiraceae）丰度的显著升高呈强相关性，而后者又可平衡瘤胃球菌科相关菌种（包括罗斯氏菌属Roseburia sp.）以及嗜胆菌属（Bilophila）的丰度。罗斯氏菌属相对丰度的菌群稳态（eubiotic）倾向与短链脂肪酸浓度的升高呈显著正相关。短链脂肪酸还可作用于消化道的其他部位，例如肠神经系统，通过促进胃肠蠕动以缓解功能性便秘。
结论 补充源自达迪的植物乳杆菌IS-10506（1.2×10¹⁰ CFU/天）发酵乳，可改善肠道菌群平衡至稳态，并提升短链脂肪酸浓度，这是缓解女性功能性便秘症状的潜在分子机制。
关键词：益生菌、植物乳杆菌IS-10506（Lactiplantibacillus plantarum IS-10506）、女性功能性便秘、菌群谱、短链脂肪酸
副标题：功能性便秘患者的菌群谱