Gut Micriobiome May Impact Diabetes Development

Changes in the composition of the gut microbiome may contribute to the development of anti-islet autoimmunity in T1DM, according to results from the German BABYDIET study published in Microbiome. 

The results also suggested that early exposure to complex food, particularly exposure to meat, may contribute to increased risk for anti-islet cell antibodies.

“Overall, we support observations made in the prospective cohorts, that early introduction of higher food complexity increases the risk for autoimmunity,” wrote first author David Endesfelder, PhD, of the Helmholtz Center (Munich), and colleagues.

Anti-islet cell autoimmunity develops early in life, preceding the development of T1DM. While genetic background contributes to about 60% of T1DM risk, the remaining contribution may stem from environmental factors like diet and early infections, according to background information in the article.

In the postnatal period, diet can strongly affect the composition of the gut microbiome, which plays an important role in the infant’s developing immune system.  Research has yielded contradictory results about the protective role of breastfeeding in T1DM, though increasing evidence seems to support a role for early introduction of a complex diet in the development of T1DM.

In the study, researchers developed a new approach called community analysis on co-occurrence networks of bacteria, which can provide information about the contribution of diet to the composition of the gut microbiome. They analyzed 298 stool samples from 44 children aged 0.24 to 3.2 years who participated in the BABYDIET study (22 children later developed anti-islet cell antibodies, and 22 children remained antibody negative). Researchers estimated the composition of gut microbiota in these children at age 6 months, when breast feeding may stop and more complex food may be introduced. Parents self-reported their children’s daily diet.

Key results identified three main communities:

• Community 1: Dominated by Enterobacterials (38%, P<0.00001) and Lactobacillales (21%, P=0.002), and was the only community with Bifidobacteriales

♦ More balanced microbial composition

♦ High levels of breast-feeding (P=0.012), and low levels of complex diet (P=0.00006)

♦ No associations with anti-islet cell autoantibody development

• Community 2: Dominated by Clostridiales (65%, P<0.0001) and Erysipelotrichales (15%, P=0.02)

♦ Microbial composition more capable of breaking down complex polysaccharides

♦ Lower levels of breastfeeding, increased exposure to solid foods

♦ No associations with anti-islet cell autoantibody development

• Community 3: Dominated by Firmicutes (67%) and Bacteroidetes (22%, P=0.002)

♦ A subgroup dominated by Bacteroides and almost no Akkermasia had higher exposure to a complex diet, and early introduction to non-fat milk and meat

♦ The Bacteroides-dominated subgroup had significantly increased risk of early autoantibody development, compared to subgroups with low Bacteroides and increased Akkermasia (P=0.041)

♦ Levels of Bacteroides were significantly higher in children with early exposure to meat (P=0.007)

The authors pointed out that children in Akkermansia-dominated subgroups had microbiomes that favored butyrate production, compared to children in the Bacteroides-dominated subgroup.   

Akkermansia has been associated with healthier guts, though early introduction of solid food like complex carbohydrates and meat might decrease this advantage in favor of Bacteroides, they continued.  Intestinal epithelial cells use butyrate as their major energy source. Decreased levels of butyrate could impair gut integrity, contributing to “leaky gut,” in which larger molecules can breach the gut epithelial barrier. Butyrate might also directly modulate inflammation, or microbial species like Bacteroides could directly trigger immune responses from the host, they explained.

“[T]hese observations support the hypothesis that increased availability of butyrate in the intestinal tract has a protective effect on development of autoimmunity and T1D… and that this effect is associated with differences in composition of mucin-degrading bacteria and the early introduction of complex food,” they concluded.

Take-home Points

• Changes in the composition of the gut microbiome and early exposure to complex food may contribute to the development of anti-islet autoimmunity in T1DM.

• Children with gut microbiomes dominated by Bacteroides and almost no Akkermansia had higher exposure to a complex diet, and significantly increased risk of early autoantibody development.

• Children in Akkermansia-dominated subgroups had gut microbiomes that favored butyrate production, which may be protective against autoimmunity and T1DM.

• Early introduction of solid foods like complex carbohydrates and meat might offset the microbial balance in favor of Bacteroides.

Reference: Endesfelder D, et al. Towards a functional hypothesis relating anti-islet cell autoimmunity to the dietary impact on microbial communities and butyrate production. Microbiome. 2016 Apr 26;4:17.