Introduction: Pirfenidone is used for anti-fibrotic therapy of idiopathic pulmonary fibrosis (IPF). Pirfenidone causes some adverse effects (AEs) such as photosensitivity and nausea, which appear pellagra-like. Our pharmacological studies using mice had indicated that gut microbiota might play an important role in the development of these phenotypes. Here, we investigated the effect of Bifidobacterium longum BB536 on pellagra-related nausea caused by pirfenidone in our mouse model.

Aims: We investigated the role of BB536 in the development of pellagra-related nausea.

Methods: Mice kept under low-niacin diets were administered vehicle or pirfenidone (1,0 or 3.0 mg/mg/animal, twice daily, 5 days) and some mice were treated with BB536using HydroGel (a non-wetting water gel for animal hydration). The resulting nausea was evaluated based on their pica behavior and the urinary metabolite levels were analyzed using liquid chromatography coupled with mass spectrometry. Furthermore, the profiles of gut microbiota were investigated.

Results: A modulation of the gut microbiota profile caused by pirfenidone were observed, which appeared to play an important role in the development of pellagra-related nausea. A therapeutic effect of BB536 against nausea caused by pirfenidone was also identified. Finally, the urinary ratio of nicotinamide / N-methylnicotinamide was shown to be a biomarker of pellagra-like AEs induced by pirfenidone.

Conclusions: The utility of BB536 in pirfenidone-related pellagra from the viewpoint of reducing AEs was indicated. Importantly, further research is needed prior to clinical use of BB536 because its safety has not yet been evaluated in patients with IPF.