Alcohol as friend or foe in autoimmune diseases: a role for gut microbiome?

Additionally, further research has focused on the molecular mechanism of ethanol’s action on nutrient absorption, more particularly on the nutrient transporter. Dose response studies investigating the effect of mild, moderate, and heavy alcohol consumption on nutrient absorption will be important to precisely define the beneficial and detrimental role of ethanol. Most Americans have consumed alcohol at a moderate level in the past month, according to the NIAAA 27,28,130. Nevertheless, only few studies in the literature focus on long term moderate alcohol consumption and its effect on intestinal nutrient absorption. Another significant gap in the field of ethanol consumption and nutrient absorption is the lack of sex-specific data, as well as ethanol’s effect on nutrient absorption during maternal gestation and lactation 123.

Autoimmune thyroid diseases

• In addition, alcohol abuse markedly diminishes the growth hormone (GH) insulin-like growth factor (IGF-I) axis at multiple levels, including release, signaling, and cellular responses (109).
• Rates of metabolism are expressed as milli-enzymatic units (mU) per gram (g) of tissue (94, 98).
• Although the changes are specific to the species being examined (e.g., mouse, rat, human) and the alcohol consumption protocol used (e.g., chronic versus acute) there is a trend for an increase in pro-inflammatory bacteria following exposure to alcohol.

Acute alcohol ingestion induces changes in the motility of the esophagus and stomach that favor gastroesophageal reflux and, probably, the development of reflux esophagitis. Beverages with a low alcohol content stimulate gastric acid secretion, whereas beverages with a high alcohol content do not. In alcoholics this damage commonly manifests itself as an enlargement (i.e., hypertrophy) of the parotid gland, although the mechanisms leading to this condition are unknown. Moreover, alcoholics may suffer from inflammation of the tongue (i.e., glossitis) and the mouth (i.e., stomatitis). It is unclear, however, whether these changes result from poor nutrition or reflect alcohol’s direct effect on the mucosa.

Alcohol and Development of Inflammatory Bowel Disease

Other studies have indicated that an alcohol-dependent increase in the production of leukotrienes—compounds produced by the immune system that cause allergic and inflammatory reactions—also might contribute to the development of alcohol-induced mucosal injury (Bode and Bode 1992). Dietary lipid composition also has been shown to affect glucose uptake in rats fed isocaloric diets high in saturated or polyunsaturated fats. Both diets prevented the jejunal uptake of glucose, galactose, medium and long-chain fatty acids, and cholesterol in rats fed 15% ethanol in their drinking water for four weeks 125. Moreover, rats fed with a diet containing saturated fatty acids prevent the inhibitory effects of acute and chronic ethanol exposure on jejunal glucose uptake 125. Beyond these studies, no work has investigated the effect of ethanol consumption on fat absorption, specifically cholesterol, bile acids, and triglycerides, along the small intestine. Moreover, the composition of lipids in diets are important to consider when examining the overall effect of ethanol consumption on nutrient absorption 125.

Similarly contradictory results have been reported on the effect of alcohol on endocrine cells regulating acid secretion (G cells). According to one group of authors, chronic alcohol consumption reduced the number of G cells while increased gastrin plasma level in experimental animals55. On the other hand, another study found that neither acute nor chronic ethanol consumption significantly changed the number of G cells or gastrin serum level56. More than 40 years ago Roberts49 already reported that gastritis and gastroduodenal ulcer were common in alcoholics. Ethanol can cause mucosal edema, erosion, hemorrhage and necrosis by directly damaging the gastric mucosal barrier and thus affecting the ability of the gastric mucosa to defend itself by gastric acid, bile and digestive enzymes49. Recent studies demonstrated that an impaired gastric microcirculation, accompanied by increased blood levels of endothelin-1 (ET-1) and decreased levels of nitric oxide (NO) and prostaglandin (PG)E2 can critically contribute to mucosal barrier damage in a rat model50.

2. Short-Chain Fatty Acids

In this review, we will provide an overview of mechanisms of alcohol-induced endotoxemia (i.e., dysbiosis and gut leakiness) and highlight the predisposing factors (e.g., disrupted circadian rhythms) for alcohol-induced dysbiosis and gut leakiness to endotoxins. Other important gastrointestinal aspects of alcohol intake include gastroesophageal reflux disease, severely damaged gastrointestinal mucosa with hemorrhagic gastritis, and lactose intolerance. In addition, alcohol use deteriorates both celiac disease and chronic inflammatory bowel disease and affects gastrointestinal motility. Discussing all alcohol-related gastrointestinal topics may well go beyond the constraints of a focused issue. Studies in dogs found that acute alcohol administration depressed the colon’s impeding motility but enhanced its propulsive motility (Mezey 1985).

The Influence of Alcohol Consumption on Intestinal Nutrient Absorption: A Comprehensive Review

Certain bacteria that are a major source of endotoxin may overgrow the normal bacterial flora in the jejunum of alcoholics (Bode and Bode 1992). The hypothesis that bacterial overgrowth may be responsible for the development of alcohol-related organ damage has been supported by the observation that sterilization of the intestine prevents alcohol-induced liver injury in animal experiments (Adachi et al. 1995). Both acute and chronic alcohol consumption can interfere with stomach functioning in several ways.

• Alcohol may interact directly with the gastric mucosa (i.e., topical stimulation); or, it may act through a more general mechanism affecting the release of hormones and the regulation of nerve functions involved in acid secretion (Chari et al. 1993).
• In experimental animal models (rodents or dogs), even low concentration of ethanol (≥ 4%, vol/vol) damages the intestinal mucosa59.
• Patients with alcohol-related liver disease have simultaneous immune activation and exhaustion 19.
• The frequent occurrence of alcohol use disorders in the adult population and the significant and widespread detrimental organ system effects highlight the importance of recognizing and further investigating the pathophysiological mechanisms underlying alcohol-induced tissue and organ injury.
• Ethanol can cause mucosal edema, erosion, hemorrhage and necrosis by directly damaging the gastric mucosal barrier and thus affecting the ability of the gastric mucosa to defend itself by gastric acid, bile and digestive enzymes49.

Alcohol’s pro- and anti-inflammatory effects on the immune system

However, the risk for adverse effects such as tissue damage generally increases following the consumption of more than 2 ounces of alcohol, which corresponds to approximately four standard drinks (i.e., “heavy” or “excessive” drinking). Another condition affecting alcoholics is Mallory-Weiss syndrome, which is characterized by massive bleeding caused by tears in the mucosa at the junction of the esophagus and the stomach. In 20 to 50 percent of all patients, the disorder is caused by increased gastric pressure resulting from repeated retching and vomiting following excessive acute alcohol consumption (Bode and Bode 1992). A recent study suggests that alcohol also can be metabolized by bacteria residing in the large intestine (Salaspuro 1996). In this pathway, alcohol is transported to the colon via the bloodstream and converted to acetaldehyde by bacterial ADH (see figure).

Alcohol and the Liver

Alcohol (ethanol) is a small water-soluble molecule that enters the blood stream via the stomach and proximal small intestine and is then distributed throughout the body. It first enters the portal vein, which drains directly into the liver, where the greatest exposure to alcohol occurs. The liver eliminates the majority of alcohol (90%), while 2–5% is excreted unchanged in urine, sweat and breath 1. In the small intestine, alcohol decreases the muscle movements that help retain the food for further digestion (i.e., the impeding wave motility). In contrast, alcohol does not affect the movements that propel food through the intestine (i.e., the propulsive wave motility) in either alcoholics or healthy subjects. These effects may contribute to the increased sensitivity to foods with a high sugar content (e.g., candy and sweetened juices), shortened transit time, and diarrhea frequently observed in alcoholics (Bode and Bode 1992).

Excessive gastric acid production can irritate the mucosa, causing gastric pain, and result in the development of gastric ulcers. Two bands of muscle fibers (i.e., sphincters) close off the stomach to the esophagus and the intestine. Weakness alcohols role in gastrointestinal tract disorders pmc of the sphincter separating the stomach from the esophagus allows the stomach content to flow back into the esophagus. This process, which is called gastroesophageal reflux, can lead to heartburn as well as inflammation (i.e., reflux esophagitis) and even to the development of ulcers in the lower part of the esophagus.

Contradictory results exist on the effect of alcohol upon gastric emptying, depending on dose and type of beverage involved. In fact gastric emptying seems to be accelerated after a low alcohol dose while high doses of ethanol delay emptying and reduce motility52. Several reports emphasized the potential role of NO in alcohol-seeking behavior as a main target of alcohol-related GI motility disorders53,54. Studies in NO sintase knockout animals demonstrated that NO is the main inhibitory nonadrenergic noncholinergic neurotransmitter in the enteric neuronal system and that NOS inhibitors delay gastric emptying and colonic transit53. SCFAs are fatty acids with fewer than six carbon atoms, and are the product of the anaerobic fermentation of indigestible dietary fibres by the gut microbiota 20.

Acetate is converted to water and carbon dioxide mainly in peripheral tissue, which is easily excreted. A minority of alcohol is metabolised by the mitochondrial enzyme oxidation system (MEOS), through the action of the cytochrome P450 (CYP) enzyme CYP2E1, to acetaldehyde with the generation of ROS. A third minor pathway of alcohol metabolism to acetaldehyde is by the action of catalase and the conversion of H2O2 to H2O. The gut microbiota refers to the collection of bacteria in the gastrointestinal tract (GI) 36,37. Bacterial communities differ from one individual to the next due to age, dietary habits, medications, illness, stress, and geographical origin just to name a few 38,39.

Intestinal Bacterial Microflora

In many animal species, including humans, alcohol is not only degraded but also produced in the GI tract. Alcohol also is formed in the human stomach, and in patients with disturbed gastric emptying, the concentrations can be as high as 0.35 percent (i.e., about four times as high as the blood alcohol levels for intoxication) (Bode and Bode 1992). First, they produce less gastric acid and thus allow the proliferation of bacteria in the stomach. Both factors lead to an increase in the bacterial degradation of nutrients and thus an increase in alcohol production. Chronic alcohol ingestion leads to hepatic steatosis via increased hepatic lipogenesis and decreased hepatic lipolysis. Alcohol elevates the ratio of reduced NAD/oxidised NAD in hepatocytes, which interferes with mitochondrial beta oxidation of fatty acids, leading to their accumulation in hepatocytes 39.