If Hippocrates the father of modern medicine is to be believed, “All disease begins in the gut”. The gastrointestinal tract with its microbiota is a complex, open, and integrated ecosystem. It is widely accepted that healthy gut microbiota is essential for optimal health. Imbalance in the gut flora could lead to one being vulnerable to a large spectrum of infectious and non-communicable diseases, including diabetes and obesity. There is an urgent need to develop efficient strategies to prevent and treat metabolic disorders such as diabetes and obesity. In this article, we will look at the implications of gut microbiota in diabesity and review ways of achieving optimal metabolic conditions.
- What is Gut Microbiota and Gut Microbiome?
The gut microbiota is a collective term for the microbial community in the gut, whereas the gut microbiome is defined as the full collection of genes in the gut microbiota. The intestinal microbiota is known to be associated with metabolic syndrome and related comorbidities. Associated diseases including obesity, T2D, and fatty liver disease (NAFLD/NASH) all seem to be linked to altered microbial composition; however, causality has not been proven yet. This points to the potential causal and personalized role of the human gut microbiota in obesity and T2D is highly prioritized.
The gut microbiome contains an immense diversity of microorganisms, varying from bacteria as well as viruses, fungi, phages, protozoa, and archaea all colonizing our adult bodies. There is a proposed view that our microbiota is a microbial (endocrine) organ living symbiotically inside our gut. This has led to a new perspective suggesting multiple lineages capable of communicating with each other and shaping host immune-metabolism in several ways. Some of the capabilities of these “organ” are:
- The degradation of otherwise indigestible components of our diet
- harvesting of energy and nutrients
- shaping of the host immune system
- maintaining the integrity of the gut mucosal barrier
- xenobiotic metabolism
In this way, gut microbiota complement our biology in ways that are mutually beneficial.
The current research data regarding the precision/personalized nutrition suggest that dietary interventions, including administration of pre-, pro-, and syn-biotics, as well as antibiotic treatment should be individually tailored to prevent chronic diseases based on the genetic background, food and beverage consumption, nutrient intake, microbiome, metabolome, and other omic profiles.
- The gut and diet….
Diet is essential in the composition and the function of the gut microbiota. Microbiota alters rapidly when exposed to great and fast changes in diet. Short-term dietary changes such as switching between plant- and meat-based diets, or adding more than 30 grams of fiber per day to the diet, or following a diet with different fat/fiber content can change the human gut microbiota in function and composition significantly in 48 hours.
Fiber-enriched diets have been shown to improve insulin resistance in lean and in obese subjects with diabetes. However, only long-term dietary habits are effective in shaping the composition of the gut microbiota as short-term dietary interventions failed to change the major features and classification of the microbiota.
- What is the impact of Gut Microbiome in Insulin Resistance and Type 2 Diabetes?
When there is low diversity in the gut microbiome, there is a higher prevalence of obesity, insulin resistance, non-alcoholic fatty liver disease (NAFLD), and low-grade inflammation. Furthermore, low bacterial diversity was characterized by pro-inflammatory properties, suggested by the reduction in butyrate-producing bacteria and the increase in mucin-degrading bacteria. These characteristics potentially impair the gut integrity causing low-grade inflammation through endotoxemia. This low-grade inflammation of visceral adipose tissue may provide a link between obesity and insulin resistance.
Ethnic differences between human populations may also affect microbiota composition. Karlsson et al. compared data of T2D-associated metagenomes between Chinese and Swedish subjects with T2D, which indicated that different intestinal bacterial species were involved in similar metabolic functions. The authors were also able to distinguish subjects with T2D from healthy subjects, with a predictive power exceeding that of body mass index (BMI).
- What is the effect of Gut Microbiota in Lipid Metabolism?
In recent decades, it has become clear that many metabolic, inflammatory, and innate immune mechanisms are also coordinated by (dietary-derived) lipids. The nutritional importance of dietary lipids is unequivocal.
Lipid accumulation in conjunction with low-grade inflammation is a pathophysiological hallmark of atherosclerosis. There is emerging evidence that the pathophysiology of atherosclerosis is related to interpersonal gut microbiome differences. Atherosclerosis seems to be related to TMAO, which is a new marker associated with increased risk of atherosclerosis and coronary artery disease.
Other key intestinal regulators of lipid and cholesterol metabolism are bile acids, which are involved in facilitating intestinal absorption and transport of diet-derived nutrients, vitamins, and lipids. Whereas bile production takes place in the liver (and is facilitated by products derived from lipid catabolism), 95% of all bile acids will be reabsorbed in the terminal ileum and subsequently re-absorbed by the liver, constituting the so-called enterohepatic circulation.
The intestinal microbiota is responsible for converting primary bile salt to secondary bile salts via bile acid de-hydroxylation. Although short courses of oral antibiotics affect intestinal microbiota composition and bile acid metabolism in humans, we found differential effects on glucose metabolism.
- What effect does the Gut Microbiome have on Appetite?
Obesity is defined as an imbalance between energy intake (usually food intake) and energy expenditure. The brain is a key regulator in detecting alterations in energy balance and induces behavioral and metabolic responses to correct these alterations. The hypothalamus plays an important role in regulation of both food intake as well as energy homeostasis, receiving hormonal and (vagal) neuronal information from the periphery.
Changing the gut microbiome composition with prebiotics has also been shown to affect portal vein levels of other hormones including GLP-1, which in turn affected food intake, followed by a decrease in body weight and fat mass.
- What are the Microbial Signatures in T2DM and Obesity?
Dysbiosis, which is the disruption of normal microbiota, has been described to be involved in a large spectrum of diseases, including diabetes, obesity, and insulin resistance, through disturbing the energy balance. It has therefore been suggested that the modulation of microbiota, either directly (by antimicrobials, diet, prebiotics and/or probiotics, stool transplant, microbial-derived signaling molecules or metabolites) or indirectly (e.g., immunotherapy) may contribute to the therapeutic management of these pathologies.
- What is the Influence of Diet on Gut Microbiota in Diabetes and Obesity?
Diet is one of the major lifestyle factors involved in the genesis, prevention and control of diabetes, obesity and other cardiometabolic diseases, being also strongly linked to changes in microbiota. Many reports have shown that the genetic susceptibility to obesity may have interacted with an obesogenic environment (e.g., a major shift in dietary patterns influencing the gut microbiota, a sedentary lifestyle and physical inactivity) in determining the obesity epidemic. To date, there are many popular diets including Mediterranean, gluten-free, vegan, Western, omnivore, vegetarian. To date, most of these diets have been clearly linked to different microbiome profiles.
Following the industrial revolution, countries in the West underwent a nutritional transition from the traditional diet to a diet rich in heavily processed foods, fats, sugars, proteins, plus different additives, while remaining low in micronutrients and dietary fibers (also referred to as Western diet). These diets were deficient of dietary fibers, which are essential for gut health due to their role in stimulation of the growth and/or activity of certain beneficial microorganisms.
Conversely, people in traditional societies, with a fiber intake of almost 50–120 g/day harbor a much more diverse gut microbiota, which indicates good health. SCFAs are found in lower amounts in individuals consuming a Western diet. Western diet was correlated with a decrease in the total bacterial load and in beneficial commensals. On the other hand, subjects consuming vegan and vegetarian diets which are rich in fermentable plant-based foods were reported to have a microbiota characterized by a lower abundance of Bacteroides sp. and Bifidobacterium sp.
The Mediterranean diet (vegetables, moderate consumption of poultry, olive oil, cereals, legumes, winenuts, fish and a low amount of red meat, dairy products, and refined sugars) provides beneficial effects through the elevated content in mono-unsaturated and poly-unsaturated fatty acids, as well as high levels of antioxidants, fibers and vegetable protein content. The gut microbiota in individuals receiving Mediterranean diet is characterized by a high colonization by Lactobacillus sp., Bifidobacterium sp., and Prevotella sp., and low levels of Clostridium sp, species which are associated with weight loss, improvement of the lipid profile and decreased inflammation.
Dietary proteins have also been reported to be involved in shaping the microbiota. Individuals consuming a diet rich in beef had high levels of Bacteroides sp. and Clostridia and were low in Bifidobacterium adolescentis unlike individuals eating a meatless diet. Several studies have recently shown that diets including vegetarian whey/pea protein, and animal protein (meats, eggs, and cheese) are linked with microbial diversity. Consumption of animal-based protein was positively associated to a richness in bile-tolerant anaerobes, including Alistipes sp., Bilophila sp., and Bacteroides sp.
- What are the Future Perspective on the Gut Microbiome?
Accumulating evidence suggests that gut microbiota plays a significant role in the initiation and progression of MS. The gut microbiota was proven to modulate plasma glucose, appetite, serum lipids and pro-inflammation. In addition, prebiotics or probiotics, which are widely used to manipulate the microbiota, can reduce low-grade intestinal inflammation and improve gut barrier integrity to reduce plasma glucose and serum lipid levels, induce weight loss and decrease insulin resistance. Based on these current achievements, the gut microbiota may be a potential therapeutic target for MS. However, clinical trials addressing the efficacy and efficiency of current or potential treatments on therapeutic applications in metabolic syndrome are needed.
Also, Individuals who are obese are likely to have an imbalance in gut microbiota composition. This possibility is a thrilling avenue for further research and possible novel treatment targets. However, because most studies have been undertaken in animals, direct translation of the findings to human is limited.
Prebiotics or other newly identified beneficial bacterial strains are potential interventions that will be used for treatment in the near future, and it will be important to evaluate their efficacy. Similarly, interventional studies with metabolites of microbiota will be performed (including SCFA butyrate supplementation) to evaluate if this compound has similar effects on food intake, energy expenditure, and improved metabolic features in humans.
The modifiable effects of the human gut microbiota on the development of metabolic syndrome make its handling a promising therapeutic approach. Analyzing and mapping individual microbial composition on a metagenomic level provides insight into specific targets for treatment and contributes to personalized therapeutic interventions.
References
- Frontiers in Nutrition: Gut Microbiota, Host Organism, and Diet Trialogue in Diabetes and Obesity. Retrieved from https://www.frontiersin.org/articles/10.3389/fnut.2019.00021/full
- NCBI (2018): The Gut Microbiome as a Target for the Treatment of Type 2 Diabetes. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013535/
- NCBI (2017): Gut microbiota as a potential target of metabolic syndrome: the role of probiotics and prebiotics https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655955/
