Diabetes and the Gut Biome

Research status: Strong

The relationship between type-2 diabetes and the gut microbiome is well-summarized by Allin et. al in a literature review published in the journal Mechanisms in Endocrinology:

"Perturbations of the composition and function of the gut microbiota have been associated with metabolic disorders including obesity, insulin resistance and type 2 diabetes...

While mechanistic studies on mice collectively support a causal role of the gut microbiota in metabolic diseases, the majority of studies in humans are correlative of nature and thus hinder causal inferences. Importantly, several factors known to influence the risk of type 2 diabetes, e.g. diet and age, have also been linked to alterations in the gut microbiota complicating the interpretation of correlative studies.

However, based upon the available evidence, it is hypothesised that the gut microbiota may mediate or modulate the influence of lifestyle factors triggering development of type 2 diabetes."

We can conclude there is a large association between gut microbiome imbalances and type 2 diabetes, but the exact mechanisms, while suspected with a high level of certainty in mice, remain to be confirmed in humans.

However, several studies have established with high certainty that probiotics reduce oxidative stress (P<0.001) and insulin sensitivity (P<0.05) in type 2 diabetics.

Selected scientific literature:

1. [Review] Mechanisms in endocrinology: Gut microbiota in patients with type 2 diabetes mellitus.
  • “While mechanistic studies on mice collectively support a causal role of the gut microbiota in metabolic diseases, the majority of studies in humans are correlative of nature and thus hinder causal inferences. Importantly, several factors known to influence the risk of type 2 diabetes, e.g. diet and age, have also been linked to alterations in the gut microbiota complicating the interpretation of correlative studies. However, based upon the available evidence, it is hypothesised that the gut microbiota may mediate or modulate the influence of lifestyle factors triggering development of type 2 diabetes."
2. [Human] Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome.
  • "Alterations in intestinal microbiota are associated with obesity and insulin resistance. We studied the effects of infusing intestinal microbiota from lean donors to male recipients with metabolic syndrome on the recipients' microbiota composition and glucose metabolism. Subjects were assigned randomly to groups that were given small intestinal infusions of allogenic or autologous microbiota. Six weeks after infusion of microbiota from lean donors, insulin sensitivity of recipients increased (median rate of glucose disappearance changed from 26.2 to 45.3 μmol/kg/min; P < .05) along with levels of butyrate-producing intestinal microbiota. Intestinal microbiota might be developed as therapeutic agents to increase insulin sensitivity in humans; www.trialregister.nl; registered at the Dutch Trial Register (NTR1776)."
3. [Human] Effects of synbiotic food consumption on metabolic status of diabetic patients: a double-blind randomized cross-over controlled clinical trial.
  • "Consumption of a synbiotic food, compared to the control, resulted in a significant decrease in serum insulin levels (changes from baseline: [Probiotic, difference from baseline] -1.75 ± 0.60 vs. [Control] +0.95 ± 1.09 μIU/mL, P = 0.03). Although we failed to find a significant effect of synbiotic food consumption on total- and LDL-cholesterol levels and HOMA-IR, the effects on FPG (22.3 vs. 4.2 mg/dL, P = 0.09), serum triglycerides (45.9 vs. 20.6 mg/dL, P = 0.08) and HDL-cholesterol levels (3.1 vs. -2 mg/dL, P = 0.06) tended to be significant. A significant reduction in serum hs-CRP [high-sensitivity C-reactive protein] levels (-1057.86 ± 283.74 vs. 95.40 ± 385.38 ng/mL, P = 0.01) was found following the consumption of synbiotic food compared with the control group. Supplementation with the synbiotic food led to a significant increase in plasma total GSH [glutathione] (319.98 vs. 19.73 μmol/L, P < 0.001) and serum uric acid levels (+0.7 vs. -0.1 mg/dL, P = 0.04) compared to the control food."
  • The reduction in serum insulin levels suggests that insulin resistance decreased after the use of probiotics. The reduction in CRP (C-reactive protein, a marker of inflammation produced by the liver) is also highly significant in showing reduced inflammation. Additionally, the synbiotic group showed highly-increased levels of Glutathione (GSH) which is a powerful antioxidant. 

4. [Review/Meta analysis] The effect of probiotic and synbiotic supplementation on biomarkers of inflammation and oxidative stress in diabetic patients: A systematic review and meta-analysis of randomized controlled trials.

  • "Pooled data from these trials demonstrated that probiotic and synbiotic consumption significantly decreased hs-CRP [high-sensitivity C-reactive protein] level (standardized mean difference [SMD]=-0.38; 95% confidence interval [CI]:-0.51,-0.24; P = 0.000) and MDA (Malondialdahyde, oxidative stress indicator) (SMD=-0.61; 95% CI: -0.89, -0.32; P = 0.000) in diabetic patients compared to placebo, but increase total antioxidant capacity (SMD = 0.31; 95% CI: 0.09, 0.52; P = 0.006), NO (nitric oxide, SMD, 0.62; 95% CI (chlorine), 0.25 to 0.99; P = 0.001) and glutathione (SMD = 0.41; 95% CI: 0.26, 0.55, P = 0.000) levels.

    The results of this systematic review and meta-analysis suggest that probiotic and synbiotic supplementation may help to improve biomarkers of inflammation and oxidative stress in diabetic patients."

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