The intestinal microbiota and the risk of prediabetes: a critical analysis of relationships and therapeutic implications
The term “microorganism” is often associated by the general population with any infectious agent, but recent microbiological studies suggest otherwise.
Billions of years of evolutionary processes among microorganisms, enhanced by the theory of “survival of the fittest,” have led to the development of a relationship of coexistence and mutual benefit between humans and their symbionts, particularly intestinal microorganisms or the intestinal microbiota.
The Human Microbiome Project (HMP) was initiated in 2007 by the National Institutes of Health (NIH). The project aimed to establish the potential role of the human microbiome and its therapeutic effects on human health.
The HMP provides critical knowledge regarding the healthy human microbiome (Huttenhower et al., 2012). One analysis suggests that bacteria make up about 10^14 times our gut, corresponding to 10 times the total number of cells that make up our body (Thursby and Juge, 2017).
The symbiotic relationship is due to the unique environment of the human intestine, which provides favorable characteristics in the form of optimal temperature and pH, as well as specific nutrients, thus allowing specific gut microorganisms, also called intestinal microbiota, to potentially survive and thrive.
In return, specific species of intestinal microbiota trigger systemic effects on a variety of physiological processes, such as strengthening our immune system by fighting pathogens, modulating the blood coagulation cascade by producing essential vitamins such as B and K, assisting in cellular metabolism, and enhancing the digestion of carbohydrates, lipids, and proteins by activating metabolic pathways (de Vos et al., 2022; Lai et al., 2022).
Any potential dysbiosis, meaning disturbance in the local population of intestinal microbiota, leads to compositional and functional changes, consequently increasing the risk of developing disorders such as immunological, hematological, carcinogenic, intestinal, and cardiovascular, particularly metabolic syndrome.
A wide range of recent research has established the importance of the intestinal microbiome in metabolic homeostatic pathways.
Other theories suggest a possible correlation between alterations in the composition of the intestinal microbiota and various health conditions, including impaired fasting glucose, disturbed glucose tolerance, increased insulin resistance, and mild inflammation.
These symptoms are often related to the onset of type 2 diabetes mellitus (T2DM) (Wu et al., 2020; Iatcu et al., 2021). Although there have been various cross-sectional studies and randomized clinical trials investigating the effects of changes in the intestinal microbiome on the development of type 2 diabetes mellitus, less emphasis has been placed on determining whether the intestinal microbiota assists in the transition from a euglycemic state to prediabetes.
Prediabetes, a preliminary state to T2DM, is characterized by altered glycemic parameters compared to a euglycemic state. On average, statistics indicate that 70% of people diagnosed with prediabetes will eventually develop T2DM during their lifetime (Tabák et al., 2012).
Furthermore, considering that by 2040 it is estimated that 642 million people could be diagnosed with type 2 diabetes mellitus (Khetan and Rajagopalan, 2018), it is essential to understand the biological progression from prediabetes to diabetes.
While genetic and environmental factors such as lifestyle largely determine whether an individual will develop this chronic condition, the involvement of the intestinal microbiome in the development of prediabetes is a relatively understudied area.
This narrative review aims to evaluate the extent and contribution of changes in the composition of the intestinal microbiota in increasing the risk of developing prediabetes.
This review aims to summarize all findings on changes in the composition of the intestinal microbiome that have been shown to occur in individuals with prediabetes and diabetes compared to normal euglycemic states.
1. Dietary factors influencing the intestinal microbiota:
High-fat and sweetener-rich diets can alter the intestinal microbiota, increasing the risk of prediabetes and diabetes. Changes in the intestinal microbiota have also been observed in individuals with type 2 diabetes, with a decrease in bacteria producing butyrate, associated with intestinal health.
2. Role of exercise in influencing the intestinal microbiota:
Regular exercise can have anti-inflammatory effects on the intestinal microbiota, improving bacterial diversity and composition. Studies on mice and individuals have shown that exercise can increase butyrate production, an indicator of intestinal health, and reduce inflammation, helping to prevent prediabetes and type 2 diabetes.
3. Prolonged use of antibiotics:
Antibiotics can cause persistent intestinal dysbiosis, resulting in an increased risk of prediabetes and diabetes. Antibiotics can alter the composition of the intestinal microbiota and promote the development of antibiotic-resistant bacteria, increasing the risk of infections and metabolic complications.
4. Alcohol-associated dysmetabolism:
Chronic alcohol consumption can lead to intestinal dysbiosis, with an increase in pathogenic bacteria and a decrease in beneficial ones. These changes in the intestinal microbiota can contribute to the development of prediabetes and type 2 diabetes, as well as increase the risk of other metabolic and inflammatory complications.
5. Preventive supplementation:
Interventions such as changes in diet, supplementation with probiotics, and the use of drugs such as metformin and acarbose can positively influence the intestinal microbiota, delaying the onset of prediabetes and type 2 diabetes. However, further research is needed to fully understand the role of these interventions in managing carbohydrate metabolism and preventing metabolic diseases.
Alteration of the intestinal microbiota has emerged as a significant risk factor associated with prediabetes and type 2 diabetes (T2DM), with data supporting its relationship with metabolic disorders. The stability of microbial diversity is crucial for the functioning of metabolic processes, and alteration can lead to pathologies such as obesity and T2DM.
Prediabetes is considered one of the underlying etiologies of metabolic syndrome, and early intervention on the intestinal microbiota could reduce the risk of developing T2DM. The use of probiotics and synbiotics in controlled clinical studies has shown promising results in maintaining microbiota homeostasis during prediabetes.
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Source: Front. Bacteriol., 12 October 2023, Sec. Molecular Bacteriology and Microbiome, Volume 2 – 2023 | https://doi.org/10.3389/fbrio.2023.1242297.
