Different oral and gut microbial profiles in those with Alzheimer's disease consuming anti-inflammatory diets

Abstract

The number of people living with Alzheimer's disease (AD) is increasing alongside with aging of the population. Systemic chronic inflammation and microbial imbalance may play an important role in the pathogenesis of AD. Inflammatory diets regulate both the host microbiomes and inflammatory status. This study aimed to explore the impact of inflammatory diets on oral-gut microbes in patients with AD and the relationship between microbes and markers of systemic inflammation. The dietary inflammatory properties and the oral and gut microorganisms were analyzed using the dietary inflammatory index (DII) and 16S RNA in 60 patients with AD. The α-diversity was not related to the DII (p > 0.05), whereas the β-diversity was different in the oral microbiomes (R² = 0.061, p = 0.013). In the most anti-inflammatory diet group, Prevotella and Olsenella were more abundant in oral microbiomes and Alistipes, Ruminococcus, Odoribacter, and unclassified Firmicutes were in the gut microbiomes (p < 0.05). Specific oral and gut genera were associated with interleukin-6 (IL)-6, complement 3 (C3), high-sensitivity C-reactive protein (hs-CRP), IL-1β, IL-4, IL-10, IL-12, and tumor necrosis factor-α (TNF-α) (p < 0.05). In conclusion, anti-inflammatory diets seem to be associated with increased abundance of beneficial microbes, and specific oral and gut microbial composition was associated with inflammatory markers.

Keywords: Alzheimer's disease; dietary inflammatory index; gut microbial; oral microbial; systemic inflammation.

Figure 1

Differences in serum IL-4 levels in different AD groups (mean ± SEM). *p < 0.05.

Figure 2

Pan/Core OTU species analysis of the oral (A) and gut microbiomes (B). The Pan/Core plot reflects the rate of emergence of species under continuous sampling. The curve flattens out as the sample size increases, indicating that species don't increase significantly with sample size.

Figure 3

The oral microbial α-diversity, as assessed with ACE (A), Chao (B), Shannon (C), and Simpson (D) indexes among three groups. PT1 (tertile 1) means the oral microbiomes of the most anti-inflammatory diet group, PT2 (tertile 2) means the oral microbiomes of the no anti-inflammatory/pro-inflammatory diet group, and PT3 (tertile 3) means the oral microbiomes of the most pro-inflammatory diet group.

Figure 4

The gut microbial α-diversity, as assessed with the ACE (A), Chao (B), Shannon (C), and Simpson (D) indexes among three groups. FT1 (tertile 1) means the gut microbiomes of the most anti-inflammatory diet group, FT2 (tertile 2) means the gut microbiomes of the no anti-inflammatory/pro-inflammatory diet group, and FT3 (tertile 3) means the gut microbiomes of the most pro-inflammatory diet group).

Figure 5

The β-diversity analysis of the oral (A) and gut (B) microbiomes among different DII tertiles in patients with AD. The PCoA based on the Bray–Curtis of β-diversity analysis is presented. PCoA, principal coordinate analysis.

Figure 6

Distribution of oral and gut microbiomes between the most anti-inflammatory diet group, no anti-inflammatory/pro-inflammatory diet group, and the most pro-inflammatory diet group. (A,B) represent the relative abundance of oral microbiomes at the phylum level and genus level, respectively; (C,D) represent the relative abundance of gut microbiomes at the phylum level and genus level, respectively.

Figure 7

Differences in the relative abundance of bacterial genera in the oral (A) and gut (B) microbiomes from the most anti-inflammatory diet group and the most pro-inflammatory diet group. The left of the figure shows the differential species between the two groups, and the right shows the difference in the mean proportions of the target species (p < 0.05).

Figure 8

Heatmap of the correlation between Spearman's analysis of inflammatory markers and the relative abundance of oral (A) and gut microbiota (B) at the genus level. Orange and gray represent positive and negative correlations, respectively, with color intensity proportional to the degree of association between indices, and numbers represent r values.