If a patient were diagnosed with liver disease, most people would think of hepatitis, a viral infection of the liver, or cirrhosis, chronic scarring of the liver often associated with heavy alcohol use [1]. However, according to the Mayo Clinic, the most common form of chronic liver disease in the United States is actually non-alcoholic fatty liver disease (NAFLD), which affects between 80 and 100 million people nationwide [2]. Despite the condition affecting around 35% of the US population, its causes remain unknown [3].
Now, due to a recent study published in Cell Metabolism, we’re closer to solving this mystery. Jing Yuan et al. of Capital Medical University observed an individual with NAFLD and auto-brewery syndrome, a condition in which the body produces alcohol from digested sugars and starches [4]. This syndrome ultimately leads to intoxication without consumption of any alcohol. While many college students would point to this as a key medical discovery for totally-not-parties, the individual presented with an ultra-high blood alcohol content level (BAC) of 400 milligrams per deciliter, or five times the legal limit of .08% [5].
Furthermore, Yuan et al. observed a high-alcohol producing strain of the typical gut bacterium Klebsiella pneumoniae in this patient, which they called HiAlc Kpn [4]. The high level of alcohol produced by HiAlc Kpn in this patient and the patient’s symptoms led the researchers to suspect a link between HiAlc Kpn and NAFLD. To test the veracity of the link, they conducted an experiment which compared mice who were exposed to HiAlc Kpn and mice who were fed ethanol, a common alcohol [4]. The mice who were exposed to HiAlc Kpn displayed signs of steatosis, or fat buildup in the liver, a common precursor to non-alcoholic fatty liver disease. The HiAlc Kpn-exposed group of mice also demonstrated elevated levels of CD4 T-cells, macrophages, and neutrophils, all of which suggest that the immune system was activated in response to the fat buildup. This immune response may further damage the liver by causing tissue damage, chronic disease, and cancer [6].
However, although these results indicate a strong correlation between HiAlc Kpn and NAFLD, researchers have yet to identify a causal relationship. Since HiAlc Kpn was found in only 61% of a Chinese cohort of patients with NAFLD, it cannot be the sole factor behind NAFLD [4]. That said, this discovery offers insight into auto-brewery syndrome and potential causes for NAFLD. Non-communicable diseases (NCDs) like cancer and NAFLD already account for 71% of annual deaths worldwide [7]. As the burden of NCDs grows, research yielding even the smallest clue becomes invaluable.
References
(2018, November 30) Alcoholic hepatitis. Mayo Clinic. Mayo Foundation for Medical Education and Research.
Spengler, E. K., and Loomba, R. (2015, September) Recommendations for Diagnosis, Referral for Liver Biopsy, and Treatment of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis. Mayo Clinic proceedings. U.S. National Library of Medicine.
(2019, August 22) Nonalcoholic fatty liver disease. Mayo Clinic. Mayo Foundation for Medical Education and Research.
Yuan, J. (2019) Fatty Liver Disease Caused by High-Alcohol Producing Klebsiella pneumoniae. Cell Metabolism 30, 675–688.
Olena, A. (2019, September 19) Gut Microbe Linked to Nonalcoholic Fatty Liver Disease. The Scientist Magazine®.
Kubes, P., and Jenne, C. (2018) Immune Responses in the Liver. Annual Review of Immunology 36, 247–277.
(2018, June 1) Non communicable diseases. World Health Organization. World Health Organization.