Alcohol has been known to interfere with the absorption of several nutrients (e.g., vitamins) and augment mucosal damage of the upper small intestine, thus contributing to malnutrition that’s frequently observed in alcoholics.
Recent evidence indicates that the gut flora plays an important role in the initiation and progression of alcoholic liver injury and in the pathogenesis of other alcohol-related diseases(1).
In addition, there’s increasing evidence that the effects of chronic alcohol consumption on the mucosal immune system of the gut contribute to immune deficiency and an increased incidence of infections(2).
In this article, we’ll investigate the latest evidence on the role alcohol plays inside our gut and how it interacts with different physiological systems within our body.
Let’s first take a look how alcohol is metabolized in the gut. Once consumed, alcohol is absorbed mainly in the upper intestinal tract by diffusion (i.e., higher concentration to lower concentration) and then enters the liver via the portal vein. The effect of alcohol on the distal small intestine and colon should largely come from its circulatory levels.
The majority of alcohol metabolism in humans occurs in the liver, within cells called hepatocytes. During social drinking, defined here as an average of two standard drinks, the body typically processes the ingested alcohol with no harmful effects.
This is achieved through a process called oxidative conversion, during which the enzyme alcohol dehydrogenase (ADH) converts alcohol into the toxin acetaldehyde.
Therefore, both the small and large intestine can be disturbed by alcohol and its metabolites as the result of its oxidative and nonoxidative metabolism. Metabolism of alcohol in the Gastrointestinal (GI) tract can lead to disruption of tissue homeostasis and cause a chronic state of intestinal inflammation(3).
A large percentage of absorption occurs in the GI tract. The GI tract is naturally permeable to allow nutrients and minerals to pass through the intestinal lining and into your bloodstream. There is also a protective layer in your GI tract that keeps toxins out of your blood. This protective intestinal lining covers more than 4,000 square feet of surface area. When it works properly, it forms a tight barrier that controls what gets absorbed into the bloodstream.
This barrier could get damaged with excessive alcohol consumption by damaging cells that line the intestinal walls, a condition known as leaky gut syndrome.
This allows partially digested food, toxins, and bugs to penetrate the tissues beneath it. In effect, this can trigger inflammation and changes in the gut flora (i.e., normal bacteria), potentially leading to problems within the digestive tract and beyond.
There is a lot of research that demonstrate modifications in intestinal bacteria and inflammation may play a role in the development of several common chronic diseases.
The intestine houses more than 500 bacterial species and achieves bacterial homeostasis when the ratio between “good” bacteria and pathogenic bacteria is appropriately balanced. “Dysbiosis” occurs when disease or environmental factors disrupt the bacterial balance(4).
Normal gut flora is disrupted when there is an overall overgrowth of bacteria and evidence indicates that alcohol promotes both dysbiosis and bacterial overgrowth(5) leading to an increase in endotoxins. These endotoxins activate proteins and immune cells that promote inflammation(6).
Evidence confirms that alcohol increases intestinal bacteria (7).
This overgrowth may be directly stimulated by alcohol, but some research indicates it could be an indirect byproduct of poor digestion and intestinal function caused by alcohol consumption. For example, some research using patients with liver cirrhosis found an association between patients with abnormal intestinal motility (the intestine’s ability to move food along) and bacterial overgrowth(8).
Other studies found a connection between alcohol, bile acid, and bacterial overgrowth. It seems that alcohol can alter bile-acid metabolism which can affect intestinal bacterial(5).
Recent evidence indicates a correlation between alcohol and negative changes in the ratio between beneficial or “good” bacteria, such as strains of Lactobacillus and Bifidobacterium, and pathogenic bacteria, such as proteobacteria and bacilli(7).
A current study found that short-term alcohol intake and long-term intake over 26 years demonstrated consistent and distinct effects on gut microbial communities, which opens the possibility that these bacteria may mediate, at least in part, the pathogenesis of alcohol associated chronic disease(9).
This was the first study that demonstrated the influence of both short and long-term alcohol intake on alterations in the gut microbial community among healthy individuals.
Chronic, excessive alcohol consumption tips the balance towards the more harmful bacteria, which can release toxins that deteriorate gut inflammation.
This imbalance of gut bacterial can lead to:
Alcohol-induced bacterial overgrowth also may increase the risk of inflammation because intestinal bacteria can independently metabolize alcohol, producing excess acetaldehyde in the colon. The increase in acetaldehyde increases production of proinflammatory alcohol metabolites(10).
As mentioned previously, the intestinal barrier regulates the passage of materials between the GI tract and the bloodstream, allowing for the absorption of key nutrients and preventing the absorption of noxious substances.
This intestinal barrier is made up of a layer of water, mucous gel, and epithelial and connective tissue. The epithelial layer can become leaky or “permeable,” allowing pathogens and other deleterious substances into the bloodstream.
Research reveals that people with alcohol use disorder have increased intestinal permeability(11) and are more likely to have liver disease(12).
This indicates that intestinal permeability may be a mediator of organ damage in some individuals with alcohol use disorder.
The increase in permeability occurs because alcohol disrupts epithelial cells and the spaces between these cells, which consist of tight junctions, the cytoskeleton, and several associated proteins (see figure below)(3).
Fig: The intestinal barrier regulates the passage of materials, including microbial products, between the inside of the intestine (where food and drink go) and the cells and blood vessels on the other side of the epithelial cell layer lining the inside of the intestine. Alcohol disrupts the intestinal barrier, increasing its permeability, in two ways: via transepithelial mechanisms (cells on the left), which allow material to pass directly through the epithelial cells, and paracellular mechanisms (cells on the right), which allow material to pass through the junctions between the epithelial cells. Alcohol and its metabolites trigger transepithelial mechanisms by damaging the cells directly and weakening cell membranes via several mechanisms including oxidative stress caused by reactive oxygen species (ROS). Alcohol’s metabolites trigger paracellular mechanisms by disrupting the proteins that create the tight junctions linking cells and proteins that stabilize cells’ cytoskeletons. Increased permeability of the intestinal barrier allows bacteria and the toxins they create to leave the gut and infiltrate other organs through the bloodstream. Figure take from Bishehsari et al.(3)
Trans-epithelial permeability is caused by direct cellular damage.
For example:
Clinical conditions associated with alcohol-induced gut inflammation are:
Alcohol consumption may also influence the course of IBD through associated gut inflammation, however, its effect in patients with IBD only has been investigated in a few small studies. Findings in this small amount of research suggest that chronic alcohol consumption could increase the long-term risk of disease flare in IBD.
It’s well established that the brain helps control the gut, and recent evidence suggests the opposite is true: the gut can influence brain function(17).
Research suggests that alcohol-induced intestinal permeability can influence psychological and cognitive function.
For instance, patients hospitalized for detoxification showed signs of intestinal permeability and also had higher levels depression and anxiety, while also scoring worse on measures of selective attention (11).
This finding suggests that some of the biological and behavioral changes seen in people with alcohol use disorder may extend from the systemic inflammatory response triggered by changes in the gut.
Although the mechanisms by how the gut-brain axis transmits the effect(s) of alcohol on the central nervous system aren’t well established, evidence indicates that systemic inflammation, similarly to alcohol-provoked leaky gut, can influence the nervous system in several ways.
It may affect neuronal function and drive some symptoms of alcohol withdrawal, including autonomic disturbances and anxiety(18).
Also, elevated cytokines caused by the inflammatory response may enter the brain and disrupt the blood-brain barrier, effectively perpetuating alcohol’s effect on the central nervous system(19).
Accumulating evidence suggests that alcohol-induced dysbiosis and gut microbiome may cause modifications in the vagal response and neuroinflammation in the central nervous system linked with alcohol-associated behaviors(20).
First of all, understand that excessive alcohol use of any type is bad for your gut health. If there is such a thing as “best” alcohol, it would be red wine because it is very rich in polyphenols. Polyphenols, such as resveratrol in the skin of red grapes, are micronutrients that are thought to have beneficial properties and act as a fuel for useful microbes living inside our bowel. Polyphenols may increase good gut bacteria and reduce inflammation. Keep in mind that polyphenols are also found in many fruits and vegetables.
A recent study questioned twins about their diet and how much and what type of alcohol they typically consumed. Results showed that red wine consumption is positively associated with gut microbiota α-diversity, which is a marker of gut health. Results also suggest that even rare consumption of red wine may be sufficient to increase α-diversity(21).
Essentially, a glass of red wine every two weeks may be beneficial.
A recent systematic review investigated human trials within the last 12 years and summarized the effects of dietary grape and wine polyphenols on gut microbiota and phenolic metabolites. They concluded that the polyphenols found in red wine had a positive effect on the microbiome(22). They also stated that too much will outweigh the benefits of those gut-loving polyphenols.
In summary, alcohol can have extremely deleterious effects on your gut if consumed in excess. The evidence indicates that it affects our gut bacteria and increases inflammation (i.e., leaky gut). This impacts how we regulate our emotions, energy levels and can cause other physical ailments such as digestive problems, constipation, food allergies and skin problems.
New research shows how excessive alcohol consumption affects the gut-brain axis and can influence our emotional state and the evidence indicates that red wine is the only ‘beneficial’ type of alcohol but should still be used in moderation.
To ensure your gut has the fuel it needs to remain balanced and healthy, be sure to get good sleep, stay hydrated, eat a wide variety of nutrient-dense food.
You can also incorporate a probiotic like Pro+ Flora Probiotic into your daily routine.
With more than 50 billion live cultures and 14 different strains,
Pro+Flora Probiotic helps you stay on point by providing your gut flora the tools and fuel they need to keep you healthy and strong!
References:
1. D.P Agarwal, H. K. S. E. (2001) Alcohol in Health and Disease,. Marcel Dekker, New York, Basel. pp 369-386
2. T.R Jerells, S. B. P. (1994) Immunotoxic effects of ethanol. in mmunotoxicology and Immunopharmacology 2nd Ed., Raven Press, New York. pp 323-347
3. Bishehsari, F., Magno, E., Swanson, G., Desai, V., Voigt, R. M., Forsyth, C. B., and Keshavarzian, A. (2017) Alcohol and Gut-Derived Inflammation. Alcohol Res 38, 163-171
4. Belizario, J. E., and Napolitano, M. (2015) Human microbiomes and their roles in dysbiosis, common diseases, and novel therapeutic approaches. Front Microbiol 6, 1050
5. Schnabl, B., and Brenner, D. A. (2014) Interactions between the intestinal microbiome and liver diseases. Gastroenterology 146, 1513-1524
6. Elamin, E. E., Masclee, A. A., Dekker, J., and Jonkers, D. M. (2013) Ethanol metabolism and its effects on the intestinal epithelial barrier. Nutr Rev 71, 483-499
7. M, C. C. C., N, L. L., C, M. F., J, L. G., D, A., C, G., G, C., S, H. P., C, M., F, S. M., J, R. N., M, M. T., A, L. B. G., and A, T. V. (2014) Comparing the effects of acute alcohol consumption in germ-free and conventional mice: the role of the gut microbiota. BMC Microbiol 14, 240
8. Chang, C. S., Chen, G. H., Lien, H. C., and Yeh, H. Z. (1998) Small intestine dysmotility and bacterial overgrowth in cirrhotic patients with spontaneous bacterial peritonitis. Hepatology 28, 1187-1190
9. Yin Cao, L. H. N., Raaj S. Mehta, Cong Wang, Xiaobin Zheng, David A. Drew,, Paul Lochhead, K. L. I., Mingyang Song, Jacques Izard, Wendy Garrett, Edward, and Giovannucci, E. R., Curtis Huttenhower, Andrew T. Chan. (2019) SHORT- AND LONG-TERM ALCOHOL INTAKE AND ALTERATIONS IN THE
GUT MICROBIOME AMONG HEALTHY INDIVIDUALS. AGA Abstracts 156, S-479-S-480,
10. Zhong, W., and Zhou, Z. (2014) Alterations of the gut microbiome and metabolome in alcoholic liver disease. World J Gastrointest Pathophysiol 5, 514-522
11. Leclercq, S., De Saeger, C., Delzenne, N., de Timary, P., and Starkel, P. (2014) Role of inflammatory pathways, blood mononuclear cells, and gut-derived bacterial products in alcohol dependence. Biol Psychiatry 76, 725-733
12. Keshavarzian, A., Holmes, E. W., Patel, M., Iber, F., Fields, J. Z., and Pethkar, S. (1999) Leaky gut in alcoholic cirrhosis: a possible mechanism for alcohol-induced liver damage. Am J Gastroenterol 94, 200-207
13. Pijls, K. E., Jonkers, D. M., Elamin, E. E., Masclee, A. A., and Koek, G. H. (2013) Intestinal epithelial barrier function in liver cirrhosis: an extensive review of the literature. Liver Int 33, 1457-1469
14. Malaguarnera, G., Giordano, M., Nunnari, G., Bertino, G., and Malaguarnera, M. (2014) Gut microbiota in alcoholic liver disease: pathogenetic role and therapeutic perspectives. World J Gastroenterol 20, 16639-16648
15. Forsyth, C. B., Voigt, R. M., and Keshavarzian, A. (2014) Intestinal CYP2E1: A mediator of alcohol-induced gut leakiness. Redox Biol 3, 40-46
16. Swanson, G. R., Sedghi, S., Farhadi, A., and Keshavarzian, A. (2010) Pattern of alcohol consumption and its effect on gastrointestinal symptoms in inflammatory bowel disease. Alcohol 44, 223-228
17. Hsiao, E. Y., McBride, S. W., Hsien, S., Sharon, G., Hyde, E. R., McCue, T., Codelli, J. A., Chow, J., Reisman, S. E., Petrosino, J. F., Patterson, P. H., and Mazmanian, S. K. (2013) Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 155, 1451-1463
18. Retson, T. A., Hoek, J. B., Sterling, R. C., and Van Bockstaele, E. J. (2015) Amygdalar neuronal plasticity and the interactions of alcohol, sex, and stress. Brain Struct Funct 220, 3211-3232
19. Banks, W. A., Gray, A. M., Erickson, M. A., Salameh, T. S., Damodarasamy, M., Sheibani, N., Meabon, J. S., Wing, E. E., Morofuji, Y., Cook, D. G., and Reed, M. J. (2015) Lipopolysaccharide-induced blood-brain barrier disruption: roles of cyclooxygenase, oxidative stress, neuroinflammation, and elements of the neurovascular unit. J Neuroinflammation 12, 223
20. Gorky, J., and Schwaber, J. (2016) The role of the gut-brain axis in alcohol use disorders. Prog Neuropsychopharmacol Biol Psychiatry 65, 234-241
21. Le Roy, C. I., Wells, P. M., Si, J., Raes, J., Bell, J. T., and Spector, T. D. (2020) Red Wine Consumption Associated With Increased Gut Microbiota alpha-Diversity in 3 Independent Cohorts. Gastroenterology 158, 270-272 e272
22. Nash, V., Ranadheera, C. S., Georgousopoulou, E. N., Mellor, D. D., Panagiotakos, D. B., McKune, A. J., Kellett, J., and Naumovski, N. (2018) The effects of grape and red wine polyphenols on gut microbiota - A systematic review. Food Res Int 113, 277-287
