Berberine has been shown to benefit those with Type II Diabetes, and the changes can be applied to everyone on the spectrum of metabolic syndrome. Berberine has two pathways, a direct effect via the circulation and an indirect effect via the modification of the microbiome.[1] Butyrate can directly lower levels of lipids and glucose in the bloodstream, and can kill pathogenic bacteria while increasing the population of beneficial bacteria.[1]

Berberine is so potently beneficial, it's comparable to metformin, the standard treatment.[3] It also has synergistic effects when combined with it.[3] It lowers FBG (fasting blood glucose), triglycerides, total cholesterol, PBG (postprandial blood glucose), and it lowered cholesterol and triglycerides significantly more than metformin did.[3] Lowering of HbA1c levels is also comparable to metformin.[3]

Insulin sensitivity was enhanced by berberine as the HOMA-IR value was reduced by nearly 50%.[3] This effect may be related to fat distribution by berberine because waist and waist/hip of the patients were decreased significantly in the absence of weight change.[3] This may be due to the fact that berberine stimulates bile acids, and the bile acid receptors which are heavily present on brown adipose tissue (the good fat which generates heat and doesn't contribute to inflammation) and even activates thermogenesis in white adipose tissue.[4] These bile acids also help to regulate non-alcoholic fatty liver disease.[5] Berberine converts white fat to brown fat, increasing energy expenditure and resting metabolic rate.[6]

One of the most significant contributors to inflammation may very well be the bad bacteria of an imbalanced microbiome. Lipopolysaccharides are a chemical created by these bacteria, and they may reach the bloodstream when the intestines are not protected with a strong mucosal barrier.[5] Increased circulating LPS can promote inflammatory responses, insulin resistance, obesity, T2D mellitus, NAFL, chronic hepatitis, and other diseases.[5] The bacterial species Akkermansia has a close symbiotic relationship with humans and animals. It lives in the intestinal mucus layer, using mucus as a source of nutrition.[5] It has been shown to increase the intestinal epithelial tight junction protein levels, which improves the intestinal barrier and thus reduces the amount of lipopolysaccharides which can escape into the bloodstream, reducing inflammation.[5] Berberine significantly increases the population of this bacteria.[1][5]

Studies have shown that berberine has beneficial effects on the immune cells of the intestinal immune system and affects the expression of several intestinal immune factors.[1] This is important because Type II Diabetes, also known as Diabetes Mellitus, is an inflammatory disease, and numerous studies have shown that inflammation is such a contributing factor to weight gain, that it could be referred to as a common and potentially unifying mechanistic cause.[2] This inflammatory state via production of pro-inflammatory cytokines, is further amplified by adipokines, though a number of studies have demonstrated that adipokines stimulate additional inflammatory responses.[2] This means that the inflammation, which leads to insulin resistance and thus further weight gain, leads to more inflammation, which leads to more insulin resistance and thus more weight gain. This is one of the situations in the body which is referred to as a cascade, a problem which triggers a cycle of problems and gets out of control.

In summary, berberine can significantly reduce inflammation, fibrosis, and the levels of lipid peroxides in the liver, increase the population of Akkermansia muciniphila, a beneficial microbe which protects the intestinal barrier, increase bile acids, increase the generation of beneficial brown fat, increase the thermogenesis in both brown and white fat, reduce blood glucose, reduce blood triglycerides and cholesterol, increase the production of butyrate by gut microbes, reduce atherosclerosis, and can directly kill bad bacteria via antimicrobial activity.

[1] https://ncbi.nlm.nih.gov/pmc/articles/PMC7933196/

[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523054/

[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2410097/

[4] https://pubmed.ncbi.nlm.nih.gov/25423280

[5] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9463479/

[6] https://www.nature.com/articles/s41419-019-1706-y

[7] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5055107/