Neuroprotective effects of cell-free supernatant from Pediococcus pentosaceus TAP041 against glycation- and inflammation-associated stress responses

Abstract Neurodegenerative diseases are increasingly associated with the convergence of oxidative, inflammatory, and glycation-associated stress pathways. The present study evaluated the stress-modulatory activity and probiotic-related characteristics of Pediococcus pentosaceus TAP041, a lactic acid bacterium isolated from citrus fruit. cell-free supernatant from P. pentosaceus TAP041 (TAP041 CFS) was assessed in in vitro models of neuronal and glial stress. In SH-SY5Y neuroblastoma cells, TAP041 CFS was associated with improved cell viability, reduced intracellular ROS accumulation, a lower Bax/Bcl-2 mRNA ratio, and increased BDNF and TH mRNA expression under methylglyoxal (MGO)- and lipopolysaccharide (LPS)-induced stress. The protective effects under N ε -(carboxymethyl)-lysine (CML) exposure were comparatively limited, with partial modulation of apoptosis-related markers in the absence of significant viability recovery. In primary rat glial cells, TAP041 CFS attenuated LPS-induced GFAP immunoreactivity and suppressed IL-6 and TNF-α expression at the transcriptional level. TAP041 CFS also exhibited ABTS radical scavenging activity, providing direct biochemical evidence for secreted antioxidant constituents. The strain demonstrated gastrointestinal stress tolerance, intestinal adhesion capacity, and a favourable safety profile, including non-hemolytic and non-cytotoxic phenotypes, absence of transferable antibiotic resistance determinants, and no known virulence factors. whole-genome sequencing identified predicted pathways for glyoxalase-mediated detoxification, antioxidant defence, and B-vitamin biosynthesis, consistent with but not directly establishing the observed phenotypes. These findings identify P. pentosaceus TAP041 as a candidate strain warranting further investigation and provide a basis for future mechanistic and in vivo studies on probiotic-derived metabolites in neurodegeneration-related stress. Key points • TAP041 CFS reduced ROS, normalized Bax/Bcl-2, and suppressed glial inflammation. • TAP041 exhibits probiotic potential with GI tolerance, adhesion, and a safe profile. • Genome predicts glyoxalase and antioxidant pathways; ABTS confirms CFS antioxidants.