Premium
Soluble Mediators Derived from Lactobacillus rhamnosus GG (LGG) Decrease Visceral Pain Hypersensitivity Induced by Early Life Stress
Author(s) -
Neufeld KarenAnne McVey,
O'Mahony Siobhain M,
Waworuntu Rosaline V,
Manurung Sarmauli,
Gross Gabriele,
Berg Brian M,
Dinan Timothy G,
Cryan John F
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1176.15
Subject(s) - lactobacillus rhamnosus , probiotic , weaning , in vivo , offspring , mannitol , visceral pain , in vitro , medicine , physiology , biology , pharmacology , microbiology and biotechnology , food science , bacteria , biochemistry , nociception , pregnancy , genetics , receptor
Maternal separation of rat pups is a robust and reliable model of early life stress that induces long‐term alterations to behavior and brain neurochemistry. These changes are particularly apparent with respect to the microbiota‐gut‐brain axis where probiotic feeding has been shown to ameliorate some of these stress‐induced alterations. It is possible that biologically relevant products of probiotic metabolism are involved in such effects, and therefore could deliver the required benefits without requiring the live organism to be present. In this study the effects of a specific preparation of soluble mediators from the probiotic Lactobacillus rhamnosus GG (LGG) were evaluated. Previously, immunomodulatory properties of this material have been demonstrated both in vitro and in vivo. Production conditions have been standardized with cultivation and downstream processing steps such as desalting, sterile filtration and lyophilization. The maternal separation protocol was conducted as described in O'Mahony et al ., 2009. Rats were separated from their mothers for 3 hrs/day from postnatal day (PND) 2 to 12. Starting at weaning (PND 21), both non‐separated (NS) and maternally separated (MS) offspring were randomized into separate experimental groups and were provided drinking water with or without supplementation of LGG soluble mediators. Supplementation of the lyophilized materials was benchmarked to the number of LGG viable cells during cultivation to give a dose equivalent to a range from 1.3×10 8 to 4.3×10 8 viable LGG/animal/day throughout the study until PND 85. Visceral hypersensitivity was assessed with the colorectal distension test conducted at PND 79. There were no differences in body weight or water and food intake across groups. MS rats demonstrated visceral hypersensitivity to colorectal distension reflected by a lower pain threshold when compared to NS rats, which was ameliorated by the LGG soluble mediators (p=0.03). There were no differences in the number of observed pain behaviors between treatment groups. Interestingly, the increased pain threshold in rats that received LGG soluble mediators was not observed in animals that received unconditioned culture medium subjected to the same processing steps as the LGG soluble mediators. This indicated the presence of specific bioactives in the culture medium secreted by LGG during growth. In conclusion, administration of LGG soluble mediators in rats reversed the altered visceral pain sensitivity induced by MS. Further studies are needed to elucidate specific mechanism of actions related to gut and brain neurochemistry. Support or Funding Information Supported by Science Foundation Ireland and Mead Johnson Nutrition.