Dysbiosis in the Gut Bacterial Microbiome of Patients with Uveitis, an Inflammatory Disease of the Eye

Abstract

Uveitis (UVT), an inflammatory disease of the eye significantly contributes to vision impairment and blindness. Uveitis is associated with systemic infectious and autoimmune diseases, but in most cases, the aetiology remains unidentified. Dysbiosis in the gut microbiome has been implicated in autoimmune diseases, inflammatory diseases, cancers and mental disorders. In a mice model of autoimmune UVT, it was observed that manipulating the gut microbiome reduces the inflammation and disease severity. Further, alterations in the bacterial gut microbiome and their metabolites were reported in UVT patients from a Chinese cohort. Hence, it is worth comparing the bacterial gut microbiome of UVT patients with that of healthy controls (HC) to ascertain whether dysbiosis of the gut microbiome has implications in UVT. Our analyses showed reduced diversity of several anti-inflammatory organisms including ,, , and members of Lachnospiraceae and Ruminococcaceae families, and enrichment of (proinflammatory) and (pathogenic) OTUs in UVT microbiomes compared to HC. In addition, decrease in probiotic and antibacterial organisms was observed in UVT compared to HC microbiomes. Heatmap and PCoA plots also indicated significant variations in the microbiomes of UVT versus HC. This is the first study demonstrating dysbiosis in the gut bacterial communities of UVT patients in an Indian cohort and suggests a role of the gut microbiome in the pathophysiology of UVT.

Implicating Dysbiosis of the Gut Fungal Microbiome in Uveitis, an Inflammatory Disease of the Eye

“…For instance, using the same set of HC, we compared the bacterial and fungal microbiomes of individuals with bacterial and/or fungal keratitis or UVT with the microbiomes of HC matched for age, gender, ethnicity, and region of origin. 4,19,30 Such an approach is advantageous since by carefully designing the experiments the same set of control individuals could be recruited for the three different ocular diseases. In this paper, the demographic and the fungal microbiome data of 24 HC was derived from the 31 individuals analyzed by us earlier 30 and was also common to 21 HC, 19 which were published earlier.…”

“…In this paper, the demographic and the fungal microbiome data of 24 HC was derived from the 31 individuals analyzed by us earlier 30 and was also common to 21 HC, 19 which were published earlier. The demographic data of 13 of the 14 UVT patients is also common to the UVT patients in Kalyana Chakravarthy et al 4…”

“…[5][6][7] Our own study also confirmed gut bacterial microbiome dysbiosis in human beings with auto-immune and idiopathic UVT. 4 Two papers 6,7 indicated that HLA B27 affects the microbiome and in turn predisposes to UVT. Systemic inflammatory diseases like asthma, diabetes, rheumatoid arthritis, ulcerative colitis, Crohn's disease, etc., have also been implicated in bacterial Interaction networks of the bacterial and fungal genera in gut microbiomes of HC and UVT patients.…”

“…29 The bacterial microbiome data of nine UVT patients and 13 HC was obtained from our earlier study. 4…”

“…A few of these studies in humans have also shown association of dysbiosis in the gut bacterial microbiome with UVT. [2][3][4] Studies in mice models also suggested a role for the gut microbiome in the pathophysiology of UVT and indicated that altering the bacterial composition would attenuate the disease. [5][6][7] The most probable mechanism by which gut microbiome influences disease pathology is through the interaction with host immune system.…”