Lactobacillus rhamnosus probiotic treatment modulates gut and liver inflammatory pathways in a hepatocellular
Iuliana Nenu1, Ioana Baldea2, Camelia Alexandra Coadă3
1Department of Functional Sciences, Physiology Discipline, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania; Regional Institute of Gastroenterology and Hepatology, Cluj-Napoca, Romania.
Background And Aims:
Hepatocellular carcinoma (HCC) is a growing global concern with an increasing incidence rate. The intestinal microbiota has been identified as a potential culprit in modulating the effects of antitumoral drugs. We aimed to assess the impact of adding Lactobacillus rhamnosus probiotic to regorafenib in mice with HCC.
Methods:
Cirrhosis and HCCs were induced in 56 male Swiss mice via diethylnitrosamine injection and carbon tetrachloride administration. Mice were divided into four groups: treated with vehicle (VC), regorafenib (Rego), L. rhamnosus probiotic, and a combination of regorafenib and probiotic (Rego-Pro). After 3 weeks of treatment, liver and intestinal fragments were collected for analysis.
Results:
Regorafenib elevated gut permeability, an effect mitigated by probiotic intervention, which exhibited a notable correlation with reduced inflammation (p < 0.01). iNOS levels were also reduced by adding the probiotic with respect to the mice treated with regorafenib only (p < 0.001). Notably, regorafenib substantially increased IL-6, TNF-a and TLR4 in intestinal fragments (p < 0.01). The administration of the probiotic effectively restored IL-6 to its initial levels (p < 0.001).
Conclusion:
Reducing systemic and intestinal inflammation by administering L. rhamnosus probiotic may alleviate tumoral resistance and systemic adverse effects.
