Background/Purpose:  We have presented evidence that the frequency of helper T (Th)17 cells increased and the cells had already been activated in vivo in patients with Behcet’s disease (BD). Major proinflammatory cytokines, such as IL-1β, IL-23 and TNFα, significantly increased IL-17 production of T cells of BD patients. Recently, some researchers clarified the relationships among several gut bacteria, skewed Th17 cell function and local inflammation in autoimmune disease models, presumably through the overproduction of several proinflammatory cytokines in the intestinal immune system. We conducted fecal metagenomic analysis of BD patients and compared the data with those of normal individuals (NI) to assess whether unfavorable compositional and functional changes of gut microbiota (Dysbiosis) exist in BD patients.

Methods:  We explored fecal microbiota of 12 patients with BD and 12 NI by sequencing of 16S rRNA gene. We calculated relative abundance of bacterial taxa and the diversity of each sample (alpha diversity) and each group (beta diversity). We compared the relative abundance of bacterial taxa with fecal secretary IgA (sIgA) concentrations and a BD disease activity index in BD patients. Then we predicted metagenome functional content from the 16S rRNA gene data using a bioinformatics software package (PICRUSt).

Results:  The sequencing data showed that the family Lactobacillaceae, the genera Bifidobacterium and Eggerthella increased significantly in BD. The order Clostridia and the genus Megamonas significantly increased in NI. Fecal sIgA concentrations increased significantly in BD patients compared with those in NI. None of the relative abundance of bacterial taxa correlated with fecal sIgA concentrations or the BD activity index of patients with BD. There was no significant difference in alpha diversity between BD and NI. An exploratory analysis showed a significant difference between the two groups (BD and NI) in beta diversity. Bacterial genome function analyses revealed that glycolysis/glycogenesis and fatty acid metabolic pathways exceeded in BD patients compared with NI.

Conclusion:  Lactic acid producing bacteria, such as Bifidobacterium and Lactobacillus, were suggested to decrease short chain fatty acid production of microbes belonging to the class Clostridia, some of which were reported to be essential for the differentiation of regulatory type T cells. Recently, glycogen and several short chain fatty acids were reported to play a role in the activation of T cells through the regulation of metabolic pathway. We suggest that low short chain fatty acid concentrations with bacterial metabolic alterations may have a relationship with the skewed Th cell differentiation of BD.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/characteristic-compositional-and-functional-alteration-of-gut-microbiota-in-patients-with-behcets-disease/