Role of piperine in arsenic-induced gut dysbiosis and associated cognitive deficits

Background and objectives Piperine is an alkaloid present in black pepper ( Piper nigrum ) with antioxidant and anti-inflammatory properties and is known to modulate gut microbiota. This study was aimed at assessing the protective effect of piperine against arsenic-induced gut dysbiosis and cognitive deficits in a mouse model. Methods Swiss albino male mice (8 wk old, 22–24 g) were randomly allocated based on body weight into four groups (n=10 per group): control, arsenic-treated (As (III), 50 ppm), arsenic+piperine (10 mg/kg, p.o.), and piperine per se, and were treated for 16 weeks. Anthropometric parameters and levels of arsenic were determined using inductively coupled plasma-mass spectrometry (ICP-MS). Cognitive function was examined using Morris water maze. Gut microbial abundance was determined using real-time PCR, and systemic inflammatory markers like corticosterone, lipopolysaccharide binding protein, and cytokines in both the serum and brain tissue homogenates were quantified using commercially available enzyme-linked immunosorbent assay (ELISA) kits. Results Arsenic-treated group exhibited the lowest time spent in the target quadrant (TSTQ), whereas piperine supplementation resulted in the maximum time. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) results showed that piperine supplementation modulated key microbial populations by increasing Firmicutes, Lactobacillus , Bacteroidetes, and Akkermansia , whereas As (III) reduced Bacteroidetes and Roseburia abundances. Arsenic also increased serum lipopolysaccharide binding protein and corticosterone levels, whereas piperine markedly attenuated these induced elevations. Interpretation and conclusions Piperine showed a beneficial effect on arsenic-induced dysbiosis and cognitive impairments, which might be mediated by modulations in gut microbiota and reduction in systemic inflammation.