Probiotic Lactobacillus rhamnosus GR-1 supplementation attenuates Pb-induced learning and memory deficits by reshaping the gut microbiota

Abstract

Lead (Pb) exposure during early life has been associated with an increased risk of neurodevelopmental disorders, including learning and memory deficits. The intestinal flora, via the microbiome–gut–brain axis, could play a significant role in the nervous system. However, the effects of probiotics on ameliorating Pb-induced learning and memory deficits are still unclear. In this study, we showed that adolescent Pb exposure (150 ppm) for 2 months impaired spatial learning and memory ability, accompanied by the decreasing diversity of gut microbiota, and the decreasing abundance of Lactobacillus at the genus level. Surprisingly, administration of the Lactobacillus rhamnosus GR-1 (1010 organisms/rat/day), not L. rhamnosus LGG or Lactobacillus reuteri RC-14, reversed learning and memory deficits induced by Pb exposure. Meanwhile, administration of the L. rhamnosus GR-1 increased the diversity of the gut microbiota composition and partially normalized the genus level of Lactobacillus, Parabacteroides, Enterococcus, and Akkermansia in Pb-exposed rats. Notably, supplementation of L. rhamnosus GR-1 decreased the gut permeability of Pb-exposed rats, reduced proinflammatory cytokines [interleukin-1β (IL-1β) and IL-6] expression, and promoted anti-inflammatory cytokines [granulocyte colony-stimulating factor (G-CSF)] expression. Interestingly, neural cell treatment with G-CSF rescued Pb-induced neurotoxicity. In general, L. rhamnosus GR-1 supplementation recovered the Pb-induced loss of intestinal bacteria (Lactobacillus), which may have reversed the damage to learning and memory ability. Collectively, our findings demonstrate an unexpectedly pivotal role of L. rhamnosus GR-1 in Pb-induced cognitive deficits and identify a potential probiotic therapy for cognitive dysfunction during early life.

Gut microbiota links to serum ferritin and cognition

“… 20 SCFAs contribute to the integrity of the blood-brain barrier, inhibiting neuroinflammation and regulating the development and function of microglia. 21 Lactobacillus rhamnosus has been associated with increased hippocampal neurogenesis, inhibiting the release of proinflammatory cytokines by the microglia, thus reducing hippocampal microgliosis and inflammation, 22 , 23 which are known to impair learning and memory. 24 In mice, supplementation with Lactobacillus rhamnosus led to improved memory and EF 22 , 23 in mice and in subjects with mild cognitive impairment.…”

Probiotic has prophylactic effect on spatial memory deficits by modulating gut microbiota characterized by the inhibitory growth of Escherichia coli

“…Therefore, by optimizing the microbial community, LGR-1 is able to influence the memory status as shown in this study. Given that the unique MGB axis mediates the specific gut-brain crosstalk, our efforts are made to delineate the mediatory route in probiotic effect, manifested by modulating the immune-microglia route (Gu et al, 2022 ). Another valuable reference is the intervention process of formulated probiotics (Xiao et al, 2020 ), which showed that IL-6/H3K27me3 played important roles in improving spatial memory.…”

“…For instance, long-term probiotic supplementation enhanced memory of middle-aged rats (O’Hagan et al, 2017 ); Lactobacillus helveticus NS8 attenuated the cognition deficits caused by restraint stress (Liang et al, 2015 ). In addition, our previous findings also indicated the positive influence of probiotics on lead-induced memory dysfunction (Xiao et al, 2020 ; Gu et al, 2022 ), but till date, no attempts have been made to interrogate their preventive roles prior to the actual damage caused by environmental insults.…”