Parents’ lifestyle habits such as consuming a high-fat diet can adversely alter their offspring’s metabolism. Unhealthy eating—and numerous other environmental elements— can induce negative changes through altered gene expression in what is called epigenetics.
Much research has focused on epigenetic modifications in major processes, including cancer and neurodegenerative diseases. In light of the soaring global rates of metabolic diseases such as Type 2 diabetes mellitus, epigenetic influences in this regard are now an area of increased interest and study.
In addition to drugs and diet, probiotics are being explored as potential agents in reversing or modifying the cues transmitted to future generations. This article investigates the potential role of probiotics in the epigenetics of Type 2 diabetes mellitus (T2DM).
Epigenetics, in brief
Epigenetics describes the occurrence of inheritance across generations through cell division without modifying the DNA’s genetic material base sequence.
Various intricate mechanisms, such as chromatin remodeling, DNA methylation, histone protein modifications, and non-coding RNA activity, are involved in making epigenetic modifications.
Fortunately, epigenetic alterations resulting from environmental and nutritional influences are not permanent—in contrast to genetic inheritance— and can be reversed, causing the disappearance of previously acquired traits. However, while intervention may avoid the negative outcomes, the propensity may remain in later generations.
Epigenetics and T2DM
Many diseases are directly associated with the nutritional milieu. A high-fat, high-sugar diet (often called the “Western diet”) can increase the risk of developing Type 2 diabetes (T2DM) as well as obesity, heart disease, and many other conditions.
T2DM
The interplay of genetics and epigenetics is significant in the development of T2DM. The disease is characterized by faulty insulin secretion by pancreatic β-cells and reduced insulin sensitivity. Multiple studies have shown that epigenetic modifications can impact the progression of this condition by changing the expression of proteins that are associated with diabetes.
For example, histone methylation is a crucial modification that can influence the formation of pancreatic β cells, insulin secretion, and sensitivity. Beneficial bacteria enrich gut microbiota, which can, in turn, create vitamins that can donate methyl groups for DNA or histone methylation.
In addition, gut microbiota may affect our epigenome by providing substrates that act as regulators of chromatin modifications, which can affect glucose control in mothers and offspring.
Most likely, other mechanisms are involved. However, based on early evidence, gut microbiota may affect the epigenetic mechanisms underlying T2DM and may be a potential new target in changing gene expression in the disease.
Probiotics and epigenetic influence on T2DM
Probiotic supplementation with several species of lactobacilli has been shown to enhance insulin sensitivity and glucose metabolism in metabolic disorders. Restoration of gut microbiota by probiotics is considered to spur the beneficial changes.
Furthermore, recent research in animals explored whether lactobacilli could influence epigenetic changes that underpin insulin resistance.
One 2020 trial supplemented high-fat diet (HFD)-induced insulin-resistant rats with a mixture of lactobacilli (Lacticaseibacillus casei, Lactobacillus gasseri, and Lacticaseibacillus rhamnosus) for 12 weeks. In addition to reducing elevated blood sugars, lipids, and insulin, supplementation altered the epigenetic profile, most notably histone methylation.
A more recent study supplemented the same rat model with L. rhamnosus for 12 weeks and then mated them. Once again, probiotic supplementation reversed metabolic and histological alterations in the rats. The regimen also prevented their transfer of disease traits to offspring.
The authors concluded: “Lactobacillus rhamnosus prevents high-fat diet induced-epigenetic alterations and improves metabolism.”
In humans, the benefit of probiotics in reversing epigenetic traits is less clear. However, one small clinical study observed that probiotic supplementation throughout pregnancy led to significantly decreased levels of DNA methylation in obesity-related genes and genes associated with insulin resistance and diabetes in both mothers and children.
Takeaway
A global public health challenge, Type 2 diabetes mellitus (T2DM) is a consequence of genetic and environmental factors. New evidence suggests that gut microbiota may have a role in altering traits passed on to offspring through epigenetic effects. Specific probiotic supplementation may potentially influence outcomes by restoring microbiota to homeostasis. However, evidence is slim, and more research is needed to explore this proposed therapeutic opportunity for using probiotics to mitigate a devastating pandemic.
Key references
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