Gut Microbial Diversity Linked to Benefit in Insulin Resistance, Lower Risk of T2D

Trudy Voortman, PhD

While previous studies have found differences in the gut microbiome may affect the development of type 2 diabetes (T2D), there is limited available data due to a small sample size.

Investigators, led by Trudy Voortman, PhD and Zhangling Chen, MD, PhD, Department of Epidemiology, Erasmus Medical Center, explored the association between gut microbiome composition with insulin resistance and T2D in 2 large population-based cohorts.

The team found the composition of gut microbiome may actually influence the development of T2D, while an increased gut microbial diversity can benefit insulin resistance and risk of T2D.

Study

The team performed an analysis from January 2018 - December 2020, with the primary outcomes including insulin resistance and T2D.

The cross-sectional study took place within 2 ongoing, population-based, prospective cohorts in the Netherlands, including the Rotterdam Study (RS) and the LifeLines-DEEP (LLD) for a total of 4671 participants.

The RS included a cohort study of participants ≥45 years (n = 3132) and the LLD was a population-based cohort of participants ≥18 years (n = 1539).

Investigators used the 16S ribosomal RNA method to measure microbiome composition in stool samples, collected between January 2012 - December 2013.

They identified α diversity using the Shannon index, richness, and Inverse Simpson index, β diversity through the Bray-Curtis dissimilarity matrix, and taxa to reflect gut microbiome composition.

They used the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and glucose and insulin were measured to calculate the assessment.

In addition, the team identified cases of T2D through fasting blood glucose concentration of ≥126 mg/dL, non-fasting blood glucose of 200 mg/dL, or the use of blood glucose-lowering drugs.

Results

Data show a total of 193 T2D cases among the 2166 participants, with 1418 from the RS study and 748 from the LLD study.

Investigators observed a lower microbiome Shannon index and richness had an association with higher HOMA-IR (Shannon index -0.06; 95% CI, -0.10 to -0.02). They noted patients with T2D had lower richness than patients without diabetes (OR 0.93; 95% CI, 0.88 - 0.99).

In addition, the β diversity was associated with insulin resistance (R2= .004, P = .002 in RS and R2 = .005, P = .002 in LLD).

Data show 12 groups of bacteria were linked to HOMA-IR or T2D.

A higher amount of christensenellaceae (β = −0.08; 95% CI, −0.12 to −0.03, P < .001), christensenellaceae R7 group (β = −0.07; 95% CI, −0.12 to −0.03, P < .001) and marvinbryantia (β = −0.07; 95% CI, −0.11 to −0.03, P < .001) was associated with lower HOMA-IR.

Moreover, an increased amount of clostridiaceae 1 (OR, 0.51; 95% CI, 0.41 - 0.65, P <.001), peptostreptococcaceae (OR, 0.56; 95% CI, 0.45 - 0.70, P < .001), C sensu stricto 1 (OR, 0.51; 95% CI, 0.40 - 0.65, P < .001), intestinibacter (OR, 0.60; 95% CI, 0.48-0.76; P < .001), or Romboutsia (OR, 0.55; 95% CI, 0.44-0.70; P < .001) was shown to have association with lower rates of T2D.

Conclusion

The team concluded a higher microbiome α diversity had an association with less T2D and lower insulin resistance in individuals without diabetes.

“An increased gut microbial diversity, along with specifically more butyrate-producing bacteria, may benefit insulin resistance and risk of type 2 diabetes,” investigators wrote. “These findings may help provide new insight into causes, mechanisms, and prevention of, as well as therapy for, type 2 diabetes.”

The study, “Association of Insulin Resistance and Type 2 Diabetes With Gut Microbial Diversity: A Microbiome-Wide Analysis From Population Studies,” was published online in JAMA Network Open.