THE GUT-LIVER AXIS
There is a bidirectional communication between the gut and the liver. These two organs communicate via the biliary tract and the portal vein. Liver products influence the gut microbiota composition, but the gut microbiota also has an impact on liver health.
The liver produces primary bile acids which are then excreted in the intestine through the gall bladder, which contribute to the absorption of fat from food intake and are also important in the preservation of microbial homeostasis. When bile acids reach the colon, the gut microbiota can transform a portion of bile acids from the liver into secondary bile acids. An impaired gut microbiota can shift the balance between primary and secondary bile acids, which in turn can alter liver signaling and cholesterol metabolism.
Intestinal permeability is also an important component in the maintenance of liver health. The gut barrier is composed of specific cells called enterocytes, that are tightly bound together to maintain the intestine’s impermeability. However, some external components like diet (alcohol intake or a fatty diet) stress, intense physical activity or changes in the gut microbiota can alter the gut barrier function, letting opportunistic microorganisms or microbial compounds enter the portal vein, a vein which is directly connected to the liver. These microbial compounds and opportunistic microorganisms, after reaching the liver, can then modify the normal gut-liver interactions and set the stage for abnormal metabolism and liver cell health.
Therefore, it is important to maintain this barrier which is key to maintain the health of the liver, along with many other organs.
The gut microbiota has also an impact on several metabolic cycles that can have impacts on liver health:
- Choline is an essential nutrient found in food that is important for the maintenance of liver metabolism. Appropriate use by a normal gut microbiome can lead to healthy fat levels in the liver, supporting long term health of the host.
- Butyrate is a short-chain fatty acid produced by gut bacteria which facilitates maintenance of the gut barrier. Healthy butyrate levels produced by a healthy gut microbiota, leads to a strong gut barrier function, maintaining normal interactions between the gut and the liver.
HOW CAN PROBIOTIC HELP IN THE MAINTENANCE OF LIVER HEALTH?
Probiotics, through their various modes of action can participate in the maintenance of liver health. First, probiotics can help maintain gut barrier integrity for normal gut-liver interactions. By competing with opportunistic microorganisms, producing antimicrobial products, and binding to epithelial cells, probiotics have been demonstrated to participate in the maintenance of gut barrier integrity. Probiotics can also support the maintenance of a healthy microflora to maintain proper choline, bile acids and short-chain fatty acids metabolism for a healthy liver. By maintaining a healthy gut microflora, probiotics can help maintain a proper choline metabolism, which assists in the excretion of VLDL in the liver and allows a normal triglyceride (main constituent of fat) metabolism. By maintaining a healthy gut microflora, probiotics can help in the maintenance of bile acid metabolism, which will allow the normal cycling of cholesterol metabolism. Finally, a healthy gut microbiota allows the normal production of butyrate by intestinal bacteria which helps in the maintenance of gut barrier integrity.
Probiotics for other uses than food and dietary supplements also showed promising results in the management of liver disease, such as Non-Alcoholic Fatty Liver Diseases (NAFLD). The intake of probiotics has been demonstrated to modify the gut microflora and ameliorate liver and blood parameters among NAFLD patients such it appears in the following clinical trials made in humans.
Bibliografía:
Malaguarnera M, Vacante M, Antic T, Giordano M, Chisari G, Acquaviva R, Mastrojeni S, Malaguarnera G, Mistretta A, Li Volti G, Galvano F. Bifidobacterium longum with fructooligosaccharides in patients with non alcoholic steatohepatitis. Dig Dis Sci. 2012 Feb;57(2):545-53. doi: 10.1007/s10620-011-1887-4. Epub 2011 Sep 8. PMID: 21901256.
A total of 66 patients were randomly and equally divided into two groups, one group received Bifidobacterium longum and lifestyle modification and was compared to the other group with lifestyle modification alone.
The patients that used B.longum significantly reduced TNF-α, CRP, serum AST levels, HOMA-IR, serum endotoxin, steatosis, and the NASH activity index.
Javadi, L. (2017). The effect of probiotic and/or prebiotic on liver function tests in patients with nonalcoholic fatty liver disease: a double blind randomized clinical trial. https://www.semanticscholar.org/paper/The-E%EF%AC%80ect-of-Probiotic-and-or-Prebiotic-on-Liver-in-Javadi-Ghavami/7bdf9a5856c66db686effff4bd048a2f4cef8e70
In this double blind, placebo-control clinical trial, 75 subjects with NAFLD.
Participants were randomly assigned in 4 groups.
Group 1 received Bifidobacterium longum (BL) and Lactobacillus acidophilus (LA), group 2 received prebiotic inulin , group 3 received probiotic and the prebiotic, and group 4 received a placebo for 3 months.
The supplementation with probiotics and prebiotics improved aminotransferase enzymes, and recovered the grade of fatty liver in NAFLD patients.
Honda, Y., Kessoku, T., Sumida, Y., Kobayashi, T., Kato, T., Ogawa, Y., Tomeno, W., Imajo, K., Fujita, K., Yoneda, M., Kataoka, K., Taguri, M., Yamanaka, T., Seko, Y., Tanaka, S., Saito, S., Ono, M., Oeda, S., Eguchi, Y., Aoi, W., … Nakajima, A. (2017). Efficacy of glutathione for the treatment of nonalcoholic fatty liver disease: an open-label, single-arm, multicenter, pilot study. BMC gastroenterology, 17(1), 96. https://doi.org/10.1186/s12876-017-0652-3
The study was an open label, single arm, multicenter, pilot trial with thirty-four NAFLD patients diagnosed. All patients first underwent intervention to improve their lifestyle habits
(diet and exercise) for 3 months, followed by treatment with glutathione (300 mg/day) for 4 months. Their blood parameters and the liver fat and were evaluated before and after glutathione treatment.
ALT triglycerides, non-esterified fatty acids, and ferritin levels significantly decreased.
Irie, M., Sohda, T., Anan, A., Fukunaga, A., Takata, K., Tanaka, T., Yokoyama, K., Morihara, D., Takeyama, Y., Shakado, S., & Sakisaka, S. (2016). Reduced Glutathione suppresses Oxidative Stress in Nonalcoholic Fatty Liver Disease. Euroasian journal of hepato-gastroenterology, 6(1), 13–18. https://doi.org/10.5005/jp-journals-10018-1159
Five patients with Fatty liver and 10 with nonalcoholic steatohepatitis were enrolled in the study. Three hundred milligrams per day of glutathione was given orally to the patients
The present pilot study demonstrated that antioxidant therapy with glutathione may reduce the pathological oxidative stress in the liver in NASH, preventing the progression from NAFLD to NASH.
Aller, R., De Luis, D. A., Izaola, O., Conde, R., Gonzalez Sagrado, M., Primo, D., De La Fuente, B., & Gonzalez, J. (2011). Effect of a probiotic on liver aminotransferases in nonalcoholic fatty liver disease patients: a double blind randomized clinical trial. European review for medical and pharmacological sciences, 15(9), 1090–1095.
Double blind randomized clinical trial with 30 patients.A tablet of Lactobacillus bulgaricus and Streptococcus thermophilus, with a randomized clinical design, improved liver aminotransferases levels in patients with NAFLD.
Abhari, K., Saadati, S., Yari, Z., Hosseini, H., Hedayati, M., Abhari, S., Alavian, S. M., & Hekmatdoost, A. (2020). The effects of Bacillus coagulans supplementation in patients with non-alcoholic fatty liver disease: A randomized, placebo-controlled, clinical trial. Clinical nutrition ESPEN, 39, 53–60. https://doi.org/10.1016/j.clnesp.2020.06.020
In a randomized, double-blind, placebo-controlled clinical trial, fifty three patients with NAFLD were randomly assigned to receive either a synbiotic or a placebo capsule for 12 weeks.
It showed that daily intake of synbiotic capsule containing B. coagulans and inulin plus lifestyle modifications (diet and exercise) issuperior to lifestyle modifications alone in reduction of hepaticsteatosis and serum level of TNF-a in patients with NAFLD.