By Atreyi Mukherji, MD, MPH, FRCPC

Private Practice, Integrative Internal Medicine & Infectious Diseases, Stoney Creek, Ontario

Dr. Mukherji reports no financial relationships relevant to this field of study.

SYNOPSIS: The long-term consumption of a healthy diet, such as the Mediterranean diet or low-fat/high complex carbohydrate diets, may exert a protective effect on the development of type 2 diabetes by changing the gut microbiota, increasing the abundance of Roseburia genera and Faecalibacterium prausnitzii, respectively.

SOURCE: Haro C, Montes-Borrego M, Rangel-Zuniga OA, et al. Two healthy diets modulate gut microbial community improving insulin sensitivity in a human obese population. J Clin Endocrinol Metab 2016;101:233-242.

Obesity is a chronic disease and its pathophysiology has been linked to changes in the gut microbiota.1 Gut microbiota are a complex and diverse ecosystem of microorganisms in the human colon that act collectively as a fully integrated organ. Gut microbiota are involved in extracting nutrients, regulating innate and adaptive immunity, and helping control energy balance.2 Animal model studies show that obesity is associated with an increase in the Firmicutes/Bacteroides bacteria ratio.1 In addition, the intestinal absorption of bacterial components, such as endotoxin lipopolysaccharides, bacterial DNA, and flagellins, activate Toll-like receptors that favor insulin resistance.3 A few studies show changes in gut microbiota by dietary intervention.4,5 The Western diet increases endotoxemia, suggesting a disruption in the intestinal barrier and an increase in gram-negative bacteria content in the microbiota.4,6 A high-fat, high-carbohydrate diet induces endotoxemia and inflammation,4,7 whereas a high-fruit and high-fiber meal or intake of a polyphenol preparation, such as resveratrol, does not induce such changes.8,9

The objective of the Haro et al trial was to study the changes in gut microbiota after one year of consumption of two healthy diets: the Mediterranean diet (MedDiet) or the low-fat, high complex carbohydrate (LFHCC) diet in 20 obese patients with coronary heart disease (CHD). The study was conducted in a subgroup of the CORDIOPREV study, an ongoing prospective, randomized, open, controlled trial in patients with stable CHD (event-free for six months prior to enrollment). Patients ranged from 20-74 years of age and were excluded if they had severe CHD with life expectancy of < 5 years. All patients were on standardized treatments for CHD. The MedDiet composition was 35% fat with 22% monounsaturated fat and the LFHCC diet contained 28% fat with 12% monounsaturated fat. To ensure consistency of diet, all patients in the MedDiet group were provided olive oil. Food packs, including low-fat foods (cereal, biscuits, pasta) of similar costs, were provided to patients in the low-fat group. Plasma and fecal samples were analyzed using various molecular technologies to assess change in microbiota and metabolomic analysis.

The main findings of the study were changes in microbiota. The LFHCC diet increased Prevotella genera and decreased the Roseburia genera, whereas the MedDiet decreased the Prevotella and increased the Roseburia and Oscillospira genera (P = 0.028, 0.002, and 0.016, respectively). Parabacteroides distasonis (P = 0.025) and Faecalibacterium prausnitzii (P = 0.020) were more abundant after consumption of the MedDiet and LFHCC diet, respectively. The increase in Roseburia in the MedDiet group and the increase in F. prausnitzii in the LFHCC diet group also were accompanied by an increase in insulin sensitivity index for both diets (P = 0.019 and P = 0.005, respectively) when measured by oral glucose tolerance test performed at baseline and after one year of dietary intervention. The main metabolic changes noted in the fecal analysis were the profiles of the amino acids, peptides, and sphingolipid metabolism, which could be linked to changes in the gut microbiota.

COMMENTARY

This preliminary study showed that long-term (one-year) consumption of two heathy diets (MedDiet and LFHCC diet) was associated with changes in gut microbiota population in the colon, as well as changes in some aspects of the metabolic profile. An improvement in insulin sensitivity also was observed, as measured by the glucose tolerance test in the LHFCC diet, suggesting that these diet patterns may have a protective effect on development of type 2 diabetes.

Roseburia genera and F. prausnitzii are butyrate-producing bacteria that are found to be low in patients with type 2 diabetes. Roseburia could play an important role in gut health10 and is known to produce an anti-inflammatory effect on the gut.10-12 An antimicrobial effect through inhibiting Bacillus subtilus in the colon is another mechanism by which Roseburia genera have been shown to affect the gut microbial population in the colon.13 F. prausnitzii, along with other butyrate-producing bacteria, previously have been shown to increase in people with metabolic syndrome on the MedDiet, but not the LFHCC diet.14 The increase in Prevotella in the LFHCC diet is thought to be an adaptation of the microbiota to enhance extraction of calories from carbohydrates that escape digestion in the small intestine and are fermented in the gut.15 This also is born out in a study demonstrating Prevotella abundance with long-term diets rich in carbohydrates.16

In conclusion, the observations in this study are provocative and suggest the development of a new hypothesis about how changes in the existing gut microbiota may be one mechanism by which dietary interventions could be a therapeutic tool for chronic disease. Further studies are required to assess the effect of these findings in clinical practice. Perhaps a potential exists for a more customized (personalized) approach to the implementation of dietary interventions based on the disease and the individual patient. In the interim, clinicians should continue to utilize evidence-based dietary interventions such as the MedDiet for chronic disease, including cardiovascular disease and breast cancer.

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