Liver cirrhosis is a common end-stage consequence of diverse chronic liver diseases, with its underlying mechanisms not completely understood. Liver cirrhosis is widely prevalence and linked to significant morbidity and mortality.
It emerges following prolonged inflammation and ranks the 11th most common cause of death globally, with an approximate annual toll of a million lives.
Probiotics, lactulose, and herbal remedies have exhibited the ability to modify intestinal balance, exert anti-cirrhotic effects, and combat inflammatory factors.
Despite this, there is a scarcity of comprehensive meta-analyses examining the impact of probiotic interventions on cirrhotic patients, with most studies primarily focusing on liver function changes.
As such, researchers from Wuhan University of Science and Technology are hoping to fill the gap by analysing 33 randomised controlled trials published between 2008 and 2022, to elucidate and update the association between probiotics and cirrhosis.
The analysed trials included 1045 participants in the intervention group and 1367 participants in the control group. Their duration ranged from 1 to 48 weeks with no significant differences found between the groups.
What can probiotics do?
Of which, eight studies indicated a notable improvement in the overall clinical efficiency of cirrhosis patients through probiotic intervention (Risk Difference [RD] = 0.15, 95% Confidence Interval [CI] = 0.11–0.20, P < 0.00001).
22 studies demonstrated the effectiveness of probiotic supplements in reducing Aspartate transaminase (AST) levels (Mean Deviation [MD] = −8.77, 95% CI = −10.50 to −7.04, P < 0.00001), and a significant reduction in Alanine transaminase (ALT) was also observed (MD = −9.13, 95% CI = −10.09 to −8.18, P < 0.00001).
Additionally, 21 studies showcased lower TNF-α levels in the experimental group compared to the control group (MD = −7.76, 95% CI = −10.26 to −5.26, P < 0.00001), while 13 studies illustrated a decrease in Total bilirubin (TBIL) (MD = −6.35, 95% CI = −8.21 to −4.49, P < 0.00001).
Furthermore, 15 studies observed a significant reduction in endotoxin levels with probiotic intervention (MD = −0.19, 95% CI = −0.25 to −0.12, P < 0.00001). However, six studies reported no significant changes in IL-2 (MD = 2.95, 95% CI = −1.40 to 7.30, P = 0.18) and IL-6 (MD = −0.61, 95% CI = −5.63 to 4.41, P = 0.81).
Overall, researchers note that the intricate interplay between the enterohepatic circulation, gut microbiota, and the immune system plays a crucial role in maintaining homeostasis. Disruption of this balance, leading to increased intestinal permeability, can contribute to liver disease.
At the same time, researchers also note that there are concerns around potential infections, the transmission of drug resistance, regulatory ambiguities in probiotic products.
However, majority of the probiotic species, including Lactobacillus, Bifidobacterium, Lactococcus, and yeasts, are under the “Generally Recognized as Safe” (GRAS) category.
Caution the use of probiotics in vulnerable populations
Researchers also highlighted that the present meta-analysis encounters significant heterogeneity, particularly in metrics like IL-6, TNF-α, and TBIL.
Given the diverse timelines and participant demographics across included studies, caution is warranted when interpreting results for IL-6, TNF-α, and TBIL due to potential vast individual differences.
Moreover, only six studies contributed to the analysis of IL-2 and IL-10, revealing no significant difference, and highlighting the need for more attention to these indicators in cirrhosis research.
While probiotics' functions in cirrhosis remain unclear, understanding their role could inspire innovative therapeutic strategies. As such, the researchers urged future research to explore bioengineering technologies like compounds adsorbing specific microbiota or engineered microbiota producing anti-inflammatory molecules.
“Albeit there is no effective radical cure for cirrhosis, the results of this systematic review and meta-analysis show that the emerging networks of probiotics interventions, gut microbiota, and inflammatory factors currently prove to be possibly profitable therapeutic targets.” The researchers wrote.
“The use of probiotics in cirrhosis not only reduced liver transaminase levels but also appeared to improve inflammation and decrease pro-inflammatory markers……Probiotics are relatively safe and well tolerated, which makes them advantageous over other treatment regiments for long periods of time.”
Source: Open Life Sciences
Probiotic management and inflammatory factors as a novel treatment in cirrhosis: A systematic review and meta-analysis
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10590617/
Authors: Qinglan Xia, Yumeng Lei, Jiadun Wang, and Qiang Wang
