Tight junction modulation by Bifidobacterium bifidum: A review on the potential mechanisms of lapatinib-induced diarrhoea

Lapatinib is a targeted therapy for ErbB2-positive breast cancer. Despite its efficacy, a notable side effect associated with lapatinib is diarrhoea. Due to the prolonged duration of treatment, diarrhoea significantly impacts patients’ quality of life. A reduction in Bifidobacterium spp. levels in diarrhoea patients treated with tyrosine kinase inhibitors (TKIs) indicates an altered gut bacteria composition. However, the precise mechanisms remain unclear. This review investigates potential mechanisms behind lapatinib-induced diarrhoea through its effect on Bifidobacterium bifidum (BB) in altering the tight junctions (TJs) of the gastrointestinal (GI) tract. Scopus and PubMed searches were performed using current data from 2018 to 2024, with BB, lapatinib, diarrhoea, intestinal permeability, and TJ proteins as keywords. A total of 16 of 167 Scopus articles and 29 of 58 PubMed articles were selectively discussed. The effects of bacterial exposure and alteration of TJs in the GI tract were investigated using the in vitro model Caco-2, as these cells can spontaneously differentiate into polarised monolayers. Overall, these articles highlighted the significance of Bifidobacterium spp. studies, in maintaining intestinal homeostasis. Notably, BB plays an essential role in modulating intestinal flora and enhancing barrier function. Therefore, alterations in BB induced by lapatinib may influence TJ properties, enhance intestinal permeability, and potentially lead to diarrhoea. This review highlights the importance of understanding how lapatinib induced changes to gut microbiota and intestinal barrier function contribute to diarrhoea. Elucidating these mechanisms may help clinicians better understand the pathophysiology of TKI-induced diarrhoea and improve its management.