Biomes and Beverages: how alcohol interacts with gut microbiota
Famously, the human body contains trillions of microorganisms – in fact, ten times the number of total human cells. Together, they form a symbiotic relationship with the human body and scientists are beginning to understand more about this intricate connection. New research is increasingly pointing towards the integral role of microbiota found in our gastrointestinal tracts, which are particularly influential in the body due to their ability to release neurotransmitters and hormones into the blood.[1] These microbiota are also closely linked with the brain, forming what is known as the gut-brain axis – a bidirectional link between the brain and the gastrointestinal tract, which is beginning to receive more attention. This axis is comprised of a number of neural, endocrine and metabolic channels, including the vagus nerve and the hypothalamic-pituitary-adrenal axis.[2] When we drink alcohol, we are inadvertently affecting the quantity and diversity of our gut microbiota, which in turn has an affect upon our brain. This can then lead to behavioural changes – in particular, the kind of reward-directed behaviour related to the seeking of alcohol. This circular relationship between gut microbiota and alcohol will be explored in new findings, as well as diving deeper into how we can harness the power of gut microbiota to treat alcohol use disorders.
To examine closer the powerful influence of gut microbiota, the last decade has given rise to several important new findings about how the gut-brain axis is involved in alcohol use disorder (AUD). Alcohol dependence, which is characteristic of AUD, is often associated with an alteration to the neurological pathways in the areas of the brain responsible for reward processing.[3],[4] The cause of this neurological alteration has previously been unclear, however gut researchers have been able to shed light upon this. It is known that drinking large quantities of alcohol can damage the microbiota in the gastrointestinal tract through inflammation.[5] When the quantity and diversity of intestinal microbiota in the gut is damaged, this can lead to neuroinflammation which affects the transmission of dopamine in the brain. Dopamine is a crucial neurochemical involved in processes like motivation, memory and reward.[6] This gut-brain damage caused by drinking is particularly prevalent in the mesocorticolimbic circuit, which is an area of the brain which is heavily involved in the rewarding sensation of addictive substances. This ultimately leads to higher seeking behaviours, characteristic of those with alcohol addiction and dependence.[7] Higher rates of depression, anxiety and alcohol cravings have also been associated with this damage to microbiota.[8] Thus, this new research is able to show that drinking alcohol damages our gut microbiota, which in turn alters our brain and our resulting behaviour around alcohol. This creates another positive feedback mechanism seen in those who suffer with alcohol use disorders, making it harder for them to escape the characteristic behavioural loop.
Furthering this research, one recent study showed how the specific composition of one’s gut microbiota has a sizeable impact on how they respond to alcohol.[9] Having tested the microbiota and alcohol consumption of 507 people, along with 80 rat subjects, this study showed that heavy episodes of drinking were associated with higher quantities of Actinobacteria. However, what is particularly interesting is that when the researchers injected microbiota sourced from intoxicated rats into normal rats, this led to a higher voluntary intake of alcohol in these sober recipient rats. This suggests that alcohol-induced alteration to the gut microbiota – specifically bacteria of the genus Porphyromonas – led drinking subjects to engage in more drinking behaviour. This led to the researcher’s suggestion that the altered microbiota is affecting the brain reward system – in line with previous research about dopamine. Whilst the researchers acknowledged that correlation is not causation, these findings opened up the possibility of doing the exact opposite – injecting alcoholics with the microbiota of healthy donors to see if it might aid recovery. In other words, restoring the health of the gut microbiota to improve their alcohol-related behaviours through the vector of the gut-brain axis. Whilst this could partially be achieved by diet, researchers suggest something rather more direct. This leads us to the promising frontier of research around the injection of healthy donor gut microbiota from their fecal matter. Trials have already begun recently with fecal microbiota transplantation (FMT) for patients with alcohol use disorder. Some examples include the bacteriophage treatment of cytolysin-positive E. faecalis, or Bifidobacterium and Lactobacillus probiotic treatment. Both of which have been targeting those with alcohol-related liver disease, however there is hope that these treatments will extend to all of those struggling with alcohol use disorders.[10] Another very early clinical study showed that undergoing FMT led to a reduction in cravings, as well as the cognitive impairments and adverse psychosocial impacts which have been associated with problematic alcohol use.[11] In this trial, the donor was selected for a higher abundance of the Lachnospiraceae and Ruminococcaceae bacterial families, which aimed to restore the health of the microbiota of those with alcohol use disorder. This is very heartening research and it indicates that we are on the cusp of a novel treatment; the full potential of which has not yet been unlocked. Utilising microbiota may not only help not only those with alcohol use problems, but a wider range of other mental health and substance misuse issues.
Microbiota is emerging as a biological powerhouse which closely connects our bodies and minds. As we learn more about how alcohol affects the microorganisms in our gut, and our brains and behaviour as a result, we also learn more about how we can harness these microbiota in treatment. The most promising area of treatment currently is fecal microbiota transplantation, which has been shown to improve the behavioural and cognitive functions of those recovering from alcohol use disorders. More clinical research is critical to develop and expand the use of microbiota to treat a wider range of health issues. As we delve further into the relationship between the brain and the gut, we also move closer to seeing our body as one intricate and synergistic vessel for a whole spectrum of microorganisms.
References
[1] Neuman, H., Debelius, J.W., Knight, R., Koren, O. (2015) Microbial endocrinology: the interplay between the microbiota and the endocrine system. FEMS Microbiol Rev. 39. 509–21.
[2] Wittier Day, A., Kunamoto, C.A. (2022) Gut Microbiome Dysbiosis in Alcoholism: Consequences for Health and Recovery. Front. Cell. Infect. Microbiol. 12. 2235-2988.
[3] Rogers, G.B., Keating, D.J., Young, R.L., Wong, M.L., Licinio, J., Wesselingh, S. (2016) From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways. Mol Psychiatry. 21. 738–48.
[4] Temko, J.E., Bouhlal, S. et al. (2017) The microbiota, the gut and the brain in eating and alcohol use disorders: A ‘Menage a Trois’? Alcohol and Alcoholism. 52. 403-413.
[5] Bishehsari, F., Magno, E., et al. (2017) Alcohol and Gut-Derived Inflammation. Alcohol Res. 38(2). 163-171.
[6] González-Arancibia, C., Urrutia-Piñones, J., Illanes-González, J., Martinez-Pinto, J., Sotomayor-Zárate, R., Julio-Pieper, M., et al. (2019) Do your gut microbes affect your brain dopamine? Psychopharmacology. 236. 1611–22.
[7] Segovia-Rodríguez, L., Echeverry-Alzate, V., Rincón-Pérez, I. et al. (2022) Gut microbiota and voluntary alcohol consumption. Transl Psychiatry. 12. 146.
[8] Hsiao, E.Y., McBride, S.W., Hsien, S., et al. (2013) Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell. 155(7). 1451–1463.
[9] Segovia-Rodríguez, L., Echeverry-Alzate, V., Rincón-Pérez, I. et al. (2022) Gut microbiota and voluntary alcohol consumption. Transl Psychiatry. 12. 146.
[10] Wittier Day, A., Kunamoto, C.A. (2022) Gut Microbiome Dysbiosis in Alcoholism: Consequences for Health and Recovery. Front. Cell. Infect. Microbiol. 12. 2235-2988.
[11] Bajaj, J. S., Gavis, E. A., Fagan, A., Wade, J. B., Thacker, L. R., Fuchs, M., et al. (2021). A Randomized Clinical Trial of Fecal Microbiota Transplant for Alcohol Use Disorder. Hepatology. 73. 1688–1700.