Probiotic Lactobacilli Improves Intestinal Motility in Mice

Abstract

RationaleGastrointestinal (GI) motility is orchestrated by the enteric nervous system (ENS) organized into 2 main plexi‐sub mucosal and the myenteric plexi. Terminal differentiation of the ENS in the postnatal period is closely linked to the presence of microbiota.AimThe goal of this study was to examine if probiotics like Lactobacillus rhamnosus GG (LGG) can modulate pErk signaling in the ENS, b) regulate neuronal proliferation and/or differentiation, and thereby c) improve GI motility.MethodsThe conventional (Conv) and germ free (GF) mice were gavaged with Hanks buffer (negative control), LGG or LGG ΩSpa C (adhesion mutant of LGG). The mice were sacrificed after 2 h, and the jejunum was cryofixed and immunostained for phospho‐Erk (p44/42 MAPK, mitogen activated protein kinase). Ileum was assayed for gene expressions of neuropeptides and Hand‐2 (transcription factor regulating neuronal differentiation) by real time polymerase chain reaction (qRT‐PCR). In addition, mice gavaged with LGG, were also intra peritoneally injected with a fluorescent hydro‐cy3 dye, and production of reactive oxygen species (ROS) was assessed in the longitudinal muscle myenteric plexus (LMMP) by confocal imaging after 2 h. The conventional mice were also gavaged daily with Hanks buffer or LGG or LGG ΩSpa C for 1 week, and motility was assessed from stool frequency (stool pellets per hr) and total gastrointestinal transit time (from red carmine dye assay).ResultsWe observed that levels of pErk, Hand‐2, choline acetyl transferase (ChAT) and serotonin reuptake transporter (SERT) were significantly reduced in GF mice as compared to the Conv mice. LGG gavage resulted in enhanced phosphorylation of myenteric neuronal Erk at 2 h in both GF and Conv mice as observed from immunostaining and confocal microscopy. Further, LGG induced an upregulation of Hand‐2, and neuropeptides like ChAT and SERT in the ileum of both GF and Conv mice. The adhesion mutant LGGΩSpaC exhibited significantly reduced capacity to induce ROS, pErk, Hand‐2 and ChAT as compared to LGG in Conv mice. We observed that daily gavage of LGG, but not LGG ΩSpaC, for 1 week significantly improved gastrointestinal motility in mice as evident from motility assays.ConclusionsOur study indicates LGG can induce neuronal differentiation via ROS‐pErk signaling, and thereby improve GI motility. Hence supplementation of probiotics in the diet is beneficial for people with gastrointestinal motility disorders.Support or Funding InformationSupport: R01AI064462, R01DK089763This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.