Metformin and Its Benefits in Improving Gut Microbiota Disturbances in Diabetes Patients

Abstract

The human gastrointestinal tract presents a vastly population of microorganisms, called the microbiota. The presence of these microorganisms offers many benefits to the host, through a range of physiological functions. However, there is a potential for these mechanisms to be disrupted condition, known as dysbiosis. Recent results are showing important associations between diabetes and the gut microbiota and how the intestinal flora can influence the prognosis of this illness. Microbial intestinal imbalance has been linked to alterations in insulin sensitivity and in glucose metabolism and may play an important role in the development of diabetes. Metformin is one of the most important and widely used first-line medications for the management of type 2 diabetes (T2D). It is a complex drug with multiple sites of action and multiple molecular mechanisms. In recent years, attention has been directed to other modes of action, other than the classic ones, with increasing evidence of a major key role of the intestine. By analysing the effects of metformin on the homeostasis of the microbiota of diabetes patients, our present topic becomes one of the major importance in understanding how metformin therapy can improve gut microbiota dysbiosis and thus provide a better outcome for this illness.

Metformin, Microbiota and Health

“…237,244 In this context, a study by Ma et al demonstrated that metformin was able to restore the cognitive impairment related to obesity through the recuperation of neurogenesis by the modulation of microbiota that acted on the attenuation of neuroinflammation. 245 Moreover, this study corroborated the observation that through its action in pathologies at risk for AD, such as diabetes and obesity, 246 where metformin promoted the increase of butyrate-producing strains that were associated with intestinal integrity, 7 It could prevent bacterial products, such as LPS from accessing the host's circulatory system and causing systemic inflammation, which could favor neuroinflammation and the development of AD. 106,247…”

“…Microbial profile alterations induced by metformin in T2DM treated patients showed (1) an increase in the Firmicutes phylum, (2) an increase in the Roseburia, Butyrivibrio, and Bifidobacterium genera, (3) an increase of the strain Akkermansia muciniphila, and (4) a reduction of the Bacteroides fragilis strain. 7 By modulating the microbiota, metformin was able to (1) preserve the gastrointestinal barrier by increasing the Akkermansia muciniphila strain and reducing Lipopolysaccharide (LPS)-producing strains, such as Bacteroides fragilis, therefore enabling the production of mucus in the gastrointestinal barrier that guaranteed its integrity and reduced intestinal permeability. It also prevented the release of LPS and the subsequent activation of toll-like receptor 4 (TLR4) on the surface of the macrophages leading to an inflammatory cascade that involved the activation of JNK and IKKβ and phosphorylation of IRS-1/2, which are considered as markers of insulin resistance and damage the glucose metabolism, respectively.…”

NLRP3 Inflammasome Biomarker—Could Be the New Tool for Improved Cardiometabolic Syndrome Outcome

“…Gut microbiota changes are observed both in high-risk patients and diagnosed T2D patients. These changes interest both the composition and the function of the microbiota [60,61]. Metabolites resulted from gut microbiota activity, such as short-chain fatty acids (SCFA) have an important impact on the normal metabolic processes like insulin secretion, incretin production (GLP-1, GIP), and immune system competence.…”