Use of mouse models to evaluate the persistence, safety, and immune modulation capacities of lactic acid bacteria

Abstract

Recent clinical and experimental observations showed that specific probiotic microorganisms may provide therapeutic benefits in inflammatory bowel disease. However, a rigorous screening for new candidate probiotic strains with optimized therapeutic properties necessitates also determining possible adverse interactions with the host, particularly in individuals who are not healthy. We have evaluated the persistence of strains of lactic acid bacteria (LAB) in the digestive tracts of mice, their immunomodulation capacity, and their safety in healthy animals and in a colitis model. Following daily administration of 10(9) CFU of viable LAB orally, intragastrically, or intrarectally, the animals' feces were examined for bacterial excretion and cytokines were quantified in intestinal samples by quantitative reverse transcription-PCR. The level of bacterial translocation was assessed in healthy mice and in mice suffering from colitis induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). Irrespective of the route of administration, the potential probiotic strain Lactobacillus plantarum NCIMB8826 was found to persist for up to 10 days in the digestive tracts of mice. This strain did not induce detrimental effects in healthy or in TNBS-treated animals, as was reflected by the absence of weight loss, intestinal inflammation, modification of cytokine levels in the ileum and colon (healthy mice), and bacterial dissemination (healthy and colitic animals). Moreover, the translocation of endogenous microflora to the mesenteric lymph nodes and spleen was greatly reduced in the TNBS-treated mice after administration of LAB. This property, together with the strain's persistence capacity and innocuousness renders L. plantarum NCIMB8826 an attractive candidate as a probiotic to be used in the prevention or treatment of chronic inflammation.

Figures

FIG. 1.

Fecal counts of L. plantarum NCIMB8826, L. plantarum 256, and L. salivarius UCC118 given orally (A), intragastrically (B), or intrarectally (C) for three consecutive days (days 1 to 3). Data represented (numbers of CFU/gram of feces) are the arithmetic means ± standard errors of the means of results from three separate experiments.

FIG. 2.

Cytokine mRNA levels in the ilea (A) and the colons (B) of mice after oral administration for 4 days of carbonate buffer, L. plantarum NCIMB8826, or Lactococcus lactis MG1363. Data correspond to the means of results from eight samples and are representative of two separate experiments.

FIG. 3.

BT of the intestinal microflora in MLN and spleen. Mice received carbonate, L. plantarum NCIMB8826, or Lactococcus lactis MG1363 orally and were treated or not with TNBS-ethanol or ethanol (EtOH) by intrarectal administration. Data correspond to mean numbers of CFU per positive organ ± standard errors of the means.