Cross-species examination of single- and multi-strain probiotic treatment effects on neuropsychiatric outcomes.

Interest in elucidating gut-brain-behavior mechanisms and advancing neuropsychiatric disorder treatments has led to a recent proliferation of probiotic trials. Yet, a considerable gap remains in our knowledge of probiotic efficacy across populations and experimental contexts. We conducted a cross-species examination of single- and multi-strain combinations of established probiotics. Forty-eight human (seven infant/child, thirty-six young/middle-aged adult, five older adult) and fifty-eight non-human (twenty-five rat, twenty-seven mouse, five zebrafish, one quail) investigations met the inclusion/exclusion criteria. Heterogeneity of probiotic strains, substrains, and study methodologies limited our ability to conduct meta-analyses. Human trials detected variations in anxiety, depression, or emotional regulation (single-strain 55.6%; multi-strain 50.0%) and cognition or social functioning post-probiotic intake (single-strain 25.9%; multi-strain 31.5%). For the non-human studies, single- (60.5%) and multi-strain (45.0%) combinations modified stress, anxiety, or depression behaviors in addition to altering social or cognitive performance (single-strain 57.9%; multi-strain 85.0%). Rigorous trials that confirm existing findings, investigate additional probiotic strain/substrain combinations, and test novel experimental paradigms, are necessary to develop future probiotic treatments that successfully target specific neuropsychiatric outcomes.