Atherosclerosis, fatty liver and type 2 diabetes

Bacterial TMA producers promote arteriosclerosis

Some intestinal bacteria convert choline, carnitine and lecithin into trimethylamine (TMA). Choline, carnitine and lecithin are found, for example, in meat or eggs, but also in dietary supplements for muscle building. The TMA formed is a gas that is well absorbed and rapidly oxidized by liver enzymes to trimethylamine N-oxide (TMAO).

Elevated TMAO levels are associated with a higher risk of cardiovascular disease – especially heart attack and stroke. TMAO increases the concentration of macrophage-specific cholesterol and the formation of foam cells in the vessel wall. It also promotes inflammation of the vascular wall and increases platelet activity.⁵

Bilophila wadsworthia amplifies the adverse effects of a diet high in saturated fat. The intestinal bacterium reacts to a corresponding overnutrition with increased growth, as a recent study with overweight and obese adults has shown.¹⁰

Other intestinal bacteria can also burden the liver with their metabolic products. The concentration of iso fatty acids indicates how strongly the intestinal bacteria form hepatotoxins such as ammonia, indole¹², skatole and phenol. The substances are formed during protein breakdown - together with the branched-chain fatty acids isobutyric acid and isovaleric acid, which can be excreted and detected in the stool. Increased bacterial protein breakdown can be caused by high cell counts of proteolytic bacteria in the intestine and a diet rich in animal protein.

Prevotella copri is the intestinal bacterium that plays the most important role in the production of BCAAs - and thus also in the overall development of insulin resistance, as a Danish cohort of non-diabetic men revealed.¹⁵ In another study, Prevotella copri cell counts and LPS levels were elevated in patients with type 2 diabetes.²

The acetic acid formed by the intestinal microbiota also promotes fat storage in a high-fat diet and at the same time increases the feeling of hunger.
Studies on rats have shown that if the animals ate food with a high fat content, the intestinal microbiota produced more acetic acid. This activated the parasympathetic nervous system¹³; glucose-stimulated insulin secretion and ghrelin secretion increased. The rats ate significantly more due to the increased ghrelin secretion and the increased glucose-stimulated insulin secretion promoted energy storage in the form of fat. The rats stored fat in their skeletal muscles and liver.
But a high-sugar diet can also increase the acetic acid concentration in the intestine, since some intestinal bacteria convert simple carbohydrates into acetic acid.

Elevated levels of propionic acid in the colon, on the other hand, can prevent weight gain - especially in overweight adults. This has been shown in human studies with overweight and obese test subjects.¹⁴ The cause was increased release of hormones such as PYY and GLP-1, which reduce calorie intake. In addition, administration of propionic acid improved insulin sensitivity and reduced the concentration of the pro-inflammatory cytokine IL-8.

Studies on rats were able to uncover further mechanisms of action of propionic acid: Propionic acid seems to reverse fat-induced lipid accumulation, decrease hepatic triglyceride concentrations, and improve insulin sensitivity.¹⁴ Accordingly, propionic acid administration reduced body weight, fat mass, and white adipose tissue volume in rats despite a high-fat diet.

Increased LPS entry from the gut microbiota in a hyperpermeable gut mucosa is closely linked to the development of obesity and insulin resistance. Both are among the leading causes of cardiovascular disease, NAFLD and type 2 diabetes.³

Diet strongly influences the composition of the intestinal microbiota and thus also LPS input and butyric acid production. A diet rich in simple carbohydrates, proteins or saturated fatty acids is particularly problematic.

A rich supply of protein promotes the growth of the LPS-bearing microbiota. The lipopolysaccharides (LPS) in the outer cell membrane of Gram-negative bacteria act as endotoxins. Under certain conditions, they can pass through the intestinal barrier and develop their toxic effect.

This is exactly what happens after a meal that contains a lot of saturated fatty acids: the bacterial lipopolysaccharides diffuse into the intestinal mucosa cells together with the dietary fats. There they are packed with triglycerides, phospholipids and cholesterol into chylomicrons and transported to the blood via the lymph.³

As a recent publication has shown, the type of fatty acids is crucial for a postprandial increase in LPS concentrations.22 According to this, only the consumption of saturated fatty acids increases the LPS concentration in the blood, whereas unsaturated fatty acids protect against elevated LPS concentrations.

If the diet is high in saturated fatty acids and low in fiber over a longer period of time, the composition of the intestinal microbiota changes and the mucous membrane becomes more permeable overall. The bacteria produce less butyric acid and the intestinal mucosa lacks the nutrient it needs to maintain the functionality of the selective mucosal barrier.

If the intestinal mucosa is hyperpermeable, bacteria²³, bacterial LPS and excess hepatotoxins constantly enter the lamina propria and the bloodstream.¹ Scientists speak of metabolic endotoxemia: the endotoxin concentration is subclinically elevated over a longer period of time and the body continuously produces pro -Inflammatory cytokines released. This triggers an underlying inflammation - the silent inflammation - that can fuel insulin resistance and contribute to the development of atherosclerosis and high blood pressure.^24,3 Scientists have even identified bacterial LPS as the triggering inflammatory factor responsible for obesity and diabetes.²⁵
Persistent endotoxemia can also have a lasting impact on liver function and lead to fatty liver. Fatty liver, in turn, can progress to liver cancer without the intermediate stage of liver cirrhosis.²⁶