Correlation between gut microbiota diversity and inflammatory cytokine expression levels in Alzheimer´s disease mice

Objective To observe the changes of intestinal flora and fecal inflammatory factors in mice model of Alzheimers disease (AD).

Methods Thirty mice were divided into control group (CON group, n=18) and AD model group (AD group, n=18). Fecal samples were collected at different months of age, respectively. 16S rRNA genes high throughput sequencing was performed, and the sequencing results were analyzed for the diversity of intestinal flora. ELISA kits were used to detect the levels of IL-1β, IL-6, IL-10, IL-17A, IL-22, IL-23, TNF-α and IFN-γ in feces. The correlation between the diversity of intestinal flora and the expression levels of inflammatory factors in AD mice was analyzed.

Results There were no significant differences in intestinal flora structure of CON group among the mice aged 3, 6 and 9 months, but in the alpha diversity (OTU, Chao1, Ace, Shannon, Simpson indexes) between 3 months old AD mice and control mice (U=33.000, 35.000, 36.000, 33.000, 2.000, all P＜0.050). At the phylum level, Bacteroidetes, Proteobacteria and Tenericutes increased with age, while Firmicutes decreased with age in AD model mice at 3, 6 and 9 months of age. Lactobacillus genus in AD mice at 3, 6 and 9 months of age significantly decreased with age (H=9.871, P＜0.010), while Desulfovibrio genus significantly increased with age (H=7.906, P＜0.050). The diversity and abundance of intestinal flora in AD mice significantly changed. Lactobacillus genus significantly enriched in 3 months old AD mice. Mycoplasma and Parvibacter significantly enriched in 6 months old AD mice. Helicobacter significantly enriched in 9 months old AD mice. The concentration of fecal cytokine TNF-α in 3 months old AD mice was lower than that in 3 months old CON mice (t=4.091, P=0.005).

Conclusion There are differences in the composition of microbiota in AD mice with different months of age. Intestinal beneficial bacteria decrease with age, while pathogenic bacteria increase with age. The concentration of TNF-α in feces of 3 months oldAD mice was significantly lower than that of 3 months old CON mice.

Keywords: Alzheimers disease; Gut microbiota; High-throughput sequence; 16S rRNA; Inflammatory factor