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Gut Microbiota and Metabolic Health: The Potential Beneficial Effects of a Medium Chain Triglyceride Diet in Obese Individuals

Abstract

Sabri Ahmed Rial, Antony D. Karelis, Karl-F. Bergeron, and Catherine Mounier,

Obesity and associated metabolic complications, such as non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D), are in constant increase around the world. While most obese patients show several metabolic and biometric abnormalities and comorbidities, a subgroup of patients representing 3% to 57% of obese adults, depending on the diagnosis criteria, remains metabolically healthy. Among many other factors, the gut microbiota is now identified as a determining factor in the pathogenesis of metabolically unhealthy obese (MUHO) individuals and in obesity-related diseases such as endotoxemia, intestinal and systemic inflammation, as well as insulin resistance. Interestingly, recent studies suggest that an optimal healthy-like gut microbiota structure may contribute to the metabolically healthy obese (MHO) phenotype. Here, we describe how dietary medium chain triglycerides (MCT), previously found to promote lipid catabolism, energy expenditure and weight loss, can ameliorate metabolic health via their capacity to improve both intestinal ecosystem and permeability. MCT-enriched diets could therefore be used to manage metabolic diseases through modification of gut microbiota.

Introduction

Obesity has become an international public health problem with 2.1 billion people worldwide being overweight (body mass index (BMI) ≥ 25.0) and more than half a billion among them being obese (BMI ≥ 30.0) . Obesity is now described as a pandemic with increased prevalence in both adult and child populations. Since the 1980s, the combined prevalence of obesity and overweight increased by 28% in adults and 47% in children . Obesity is a multifactorial affection with broad etiology, and multiple comorbidities. Most of these comorbidities are thought to be the result of aberrant body fat distribution leading to the metabolic syndrome . This pathology is associated with an elevated waist circumference, a progressive state of non-alcoholic fatty liver disease (NAFLD) , insulin resistance, type 2 diabetes (T2D), some types of cancers (especially in women), hypertension, cardiovascular diseases, reproductive abnormalities, dyslipidemias, psychological affections, and a severely reduced life expectancy . Obesity is also considered a risk factor for several other diseases such as chronic respiratory diseases and arthritis.

Some contributing factors for obesity progression are: unfavorable genetic determinants , lack of physical activity , socio-economic status , circadian cycle disturbance , sleep deprivation , hormonal dysregulation, persistent organic pollutants and alteration of the gut microbiota . However, the most powerful inducer of obesity and its associated adverse metabolic effects remains, by far, inappropriate food intake. The modern prevalence of obesity and metabolic syndrome is likely due to the rise in consumption of energy-dense food, containing high amounts of fat and carbohydrates, especially in Western countries. In these countries, fats typically account for 33% to 42% of dietary energy intake, with a rich proportion of long chain saturated fat . When the energy intake exceeds both the caloric needs of the body and its glycogen storage capacity, dietary carbohydrates and fats are first converted and stored as triglycerides (TG) in white adipose tissue (WAT) and, later on, in other tissues such as the liver . Sustained and abusive accumulation of lipids in the liver induces NAFLD (highly concurrent with obesity) which may result in lipotoxicity, steatohepatitis, hepatocyte cell death, fibrosis and eventually liver cirrhosis as well as hepatocarcinoma .

Synthesis and Conclusions

This review aimed to highlight several aspects underlying the condition of obese subjects, which can be either metabolically unhealthy obese (MUHO) or metabolically healthy obese (MHO). While a panel of criteria serves to define the MUHO state, those defining metabolically healthy obesity remain the subject of current discussions. We underline the necessity of better defining the potential role of gut microbiota in the establishment of MUHO or MHO states. Moreover, we believe that gut microbiota structure may not only serve as a biomarker of those metabolic states, but can also be subjected to a diet-induced remodelling, modifying in turn the metabolic status of patients (MUHO vs. MHO or lean state). Dietary MCT, taken alone or with other supplements (such as prebiotics, probiotics, organic acids, etc.) could be used as anti-obesity interventions, in regards to their capacity to prevent intestinal permeability/endotoxemia by remodeling gut microbiota, and to prevent unhealthy storage by improving the lipid catabolism/anabolism balance. Figure 1 illustrates this concept.

Figure 1

Crosstalk between gut, liver and peripheral metabolic tissues under 4 metabolic states. Under condition of healthy leanness (A) an optimal relative abundance of LPS-expressing vs. non-expressing bacteria contribute to gut impermeability, low intestinal and hepatic inflammation, and non-obesogenic/steatogenic nutrient supply. Under MUHO conditions (B), an elevation in the relative abundance of LPS-expressing bacteria (Gram-negative) induces LPS infiltration and leads to altered intestinal barrier integrity, local inflammation, liver injury and endotoxemia. At the same time, a high fat and carbohydrate supply contributes to adiposity, hepatic steatosis and peripheral insulin resistance. In MHO subjects (C), despite an adiposity sustained by a rich diet, a balanced gut microbiota would contribute to maintain intestinal and systemic metabolic health, prevent endotoxemia, and lower hepatic injury and peripheral insulin resistance. Our hypothetical model (D) suggests that diet MCT supplementation for MUHO subjects may facilitate a shift towards an MHO-like profile by improving lipid catabolism and lowering adiposity in part, but also by remodelling the gut microbiota into a metabolically beneficial structure.

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