Jhaveri Microbiology Centre, Brien Holden Eye Research Centre, L. V. Prasad Eye Institute, Kallam Anji Reddy campus, Hyderabad, India.
Bio-Sciences R&D Division, TCS Research, Tata Consultancy Services Ltd., Pune, India.
PLoS One. 2018 Jun 22;13(6):e0199640. doi: 10.1371/journal.pone.0199640. eCollection 2018.
Dysbiosis in the gut microbiome has been implicated in several diseases including auto-immune diseases, inflammatory diseases, cancers and mental disorders. Keratitis is an inflammatory disease of the eye significantly contributing to corneal blindness in the developing world. It would be worthwhile to investigate the possibility of dysbiosis in the gut microbiome being associated with Keratitis. Here, we have analyzed fungal and bacterial populations in stool samples through high-throughput sequencing of the ITS2 region for fungi and V3-V4 region of 16S rRNA gene for bacteria in healthy controls (HC, n = 31) and patients with fungal keratitis (FK, n = 32). Candida albicans (2 OTUs), Aspergillus (1 OTU) and 3 other denovo-OTUs were enriched in FK samples and an unclassified denovo-OTU was enriched in HC samples. However, the overall abundances of these 'discriminatory' OTUs were very low (< 0.001%) and not indicative of significant dysbiosis in the fungal community inhabiting the gut of FK patients. In contrast, the gut bacterial richness and diversity in FK patients was significantly decreased when compared to HC. 52 OTUs were significantly enriched in HC samples whereas only 5 OTUs in FK. The OTUs prominently enriched in HC were identified as Faecalibacterium prausnitzii, Bifidobacterium adolescentis, Lachnospira, Mitsuokella multacida, Bacteroides plebeius, Megasphaera and Lachnospiraceae. In FK samples, 5 OTUs affiliated to Bacteroides fragilis, Dorea, Treponema, Fusobacteriaceae, and Acidimicrobiales were significantly higher in abundance. The functional implications are that Faecalibacterium prausnitzii, an anti-inflammatory bacterium and Megasphaera, Mitsuokella multacida and Lachnospira are butyrate producers, which were enriched in HC patients, whereas Treponema and Bacteroides fragilis, which are pathogenic were abundant in FK patients, playing a potential pro-inflammatory role. Heatmap, PCoA plots and functional profiles further confirm the distinct patterns of gut bacterial composition in FK and HC samples. Our study demonstrates dysbiosis in the gut bacterial microbiomes of FK patients compared to HC. Further, based on inferred functions, it appears that dysbiosis in the gut of FK subjects is strongly associated with the disease phenotype with decrease in abundance of beneficial bacteria and increase in abundance of pro-inflammatory and pathogenic bacteria.
肠道微生物组的生态失调与包括自身免疫性疾病、炎症性疾病、癌症和精神障碍在内的多种疾病有关。角膜炎是一种眼部炎症性疾病，在发展中国家显著导致角膜盲。值得研究肠道微生物组的生态失调是否与角膜炎有关。在这里，我们通过对健康对照组（HC，n=31）和真菌性角膜炎（FK，n=32）患者粪便样本中 ITS2 区的真菌和 V3-V4 区 16S rRNA 基因的高通量测序，分析了真菌和细菌种群。白色念珠菌（2 个 OTU）、曲霉（1 个 OTU）和 3 个其他新 OTU 在 FK 样本中富集，未分类的新 OTU 在 HC 样本中富集。然而，这些“有区别”的 OTU 的总体丰度非常低（<0.001%），并不能表明 FK 患者肠道中真菌群落存在明显的生态失调。相比之下，FK 患者的肠道细菌丰富度和多样性明显降低。52 个 OTU 在 HC 样本中显著富集，而 FK 样本中只有 5 个 OTU。在 HC 样本中明显富集的 OTU 被鉴定为普拉梭菌、青春双歧杆菌、lachnospira、Mitsuokella multacida、拟杆菌 plebeius、巨大球型菌和lachnospiraceae。在 FK 样本中，丰度显著较高的 5 个 OTU 属于脆弱拟杆菌、Dorea、Treponema、梭杆菌科和 Acidimicrobiales。功能意义在于，普拉梭菌是一种抗炎细菌，而巨大球型菌、Mitsuokella multacida 和lachnospira 是丁酸产生菌，它们在 HC 患者中富集，而致病性的 Treponema 和脆弱拟杆菌在 FK 患者中丰富，发挥潜在的促炎作用。热图、PCoA 图和功能谱进一步证实了 FK 和 HC 样本中肠道细菌组成的明显模式。我们的研究表明，与 HC 相比，FK 患者的肠道细菌微生物组存在生态失调。此外，根据推断的功能，FK 患者肠道的生态失调似乎与疾病表型密切相关，有益菌的丰度降低，促炎和致病性细菌的丰度增加。
