Recovery of Ggt7 and Ace Expressions in the Colon Alleviates Collagen-Induced Arthritis in Rats by Specific Bioactive Polysaccharide Intervention

Rheumatoid arthritis (RA) causes swollen joints and irreversible joint damage and may even elevate cancer risks. Several bioactive nonstarch polysaccharides (NSPs) were reported to alleviate RA, but the key colonic genes accountable for this alleviation were elusive. Using collagen-induced arthritis as an RA model, colonic candidate genes related to RA were selected by transcriptome and methylome. The key genes were determined by comparing the transcriptome, methylome, and quantitative reverse transcription polymerase chain reaction profiles in RA rats with and without Lycium barbarum polysaccharides' treatment and further validated using Angelica sinensis polysaccharides and Astragalus propinquus polysaccharides for comparison. Both colonic genes gamma-glutamyltransferase 7 (Ggt7) and angiotensin-I-converting enzyme (Ace) were downregulated by RA, and they were upregulated after L. barbarum polysaccharides' and A. sinensis polysaccharides' intervention that reduced the RA-caused hypermethylation status in nucleotide sites in the exon/promoter region of the two genes. However, the A. propinquus polysaccharides' intervention barely reduced the hypermethylation in the corresponding sites, failing to recover the expressions of these two genes and improve RA. Therefore, the colonic Ggt7 and Ace can be considered as key genes accountable for RA alleviation by bioactive NSP intervention. This study provides a more comprehensive insight into diet intervention to improve RA.