Assessment of Safety ofLactobacillusStrains Based on Resistance to Host Innate Defense Mechanisms

Abstract

Seven Lactobacillus strains belonging to four species were evaluated for pathogenicity as well as for in vitro sensitivity to the bactericidal mechanisms of macrophages in a rabbit infective endocarditis (IE) model. Two bacteremia-associated strains, L. rhamnosus PHLS A103/70 and L. casei PHLS A357/84, as well as the L. rhamnosus type strain and the probiotic L. rhamnosus strain ATCC 53103, showed moderate infectivity, and the virulence of the probiotic L. casei strain Shirota and type strains such as L. acidophilus ATCC 4356 T and L. gasseri DSM 20243 T in the model was negligible. The strains that showed pathogenic potential in the rabbit IE model (PHLS A357/84, PHLS A103/70, and ATCC 53103) were more resistant than strain Shirota to intracellular killing activity by mouse macrophages in vitro and also to bactericidal nitrogen intermediates, such as nitric oxide and NO 2 ؊ ions. These results suggest that resistance to host innate defense systems, which would function at inflammatory lesions, should be considered in the safety assessment of Lactobacillus strains.The widespread use of lactic acid bacteria (LAB) in fermented foods and dairy products has a long history, and most strains are considered commensal microorganisms with no pathogenic potential. Members of the genus Lactobacillus in particular have been shown to inhabit the human gastrointestinal tract, and the long history of safe use of many species of lactobacillus gave them generally-recognized-as-safe status (13, 23).However, some cases of local or systemic infections, including septicemia, meningitis, and endocarditis, due to LAB have been reported, but they account for only a very small number of bacteremia cases (the incidence of causation is 5 to 15% for enterococci and 0.1% for lactobacilli) (12,21,22). Moreover, most LAB strains linked to clinical cases belong to the species Enterococcus faecium and E. faecalis, but a few belong to L. rhamnosus, L. casei or L. paracasei, and L. plantarum (1,8). Infective endocarditis (IE) is the most common infection to be associated with lactobacilli, and recent reports show that relatively restricted species of Lactobacillus, such as L. casei and L. rhamnosus, are the most commonly associated with IE, although the frequency of occurrence of Lactobacillus endocarditis is very low, as evidenced by previous studies (for reviews, see reference 8). A European Union-sponsored workshop organized by the Lactic Acid Bacteria Industrial Platform examined these infections and judged that in all cases reported thus far, only patients with abnormal heart valves or immunocompromised states appeared to be infected with the patients' own indigenous lactic acid bacteria. The workshop concluded that the risk of infection due to all LAB, excluding enterococci, is very low when they are ingested (1, 17). Nevertheless, the workshop also proposed that the safety of each strain should be checked by appropriate methods.In the present report, we describe the results of the assessment of the safety of seven Lactobacillus strains bel...

Nitric oxide (NO) production in mammalian non-tumorigenic epithelial cells of the small intestine and macrophages induced by individual strains of lactobacilli and bifidobacteria

“…In contrast to the report of Korhonen et al, we found that L. rhamnosus acts antagonistically to IFN-g in NO production by pig alveolar macrophages (Asahara et al, 2003;Erickson & Hubbard, 2000;Korhonen et al, 2001Korhonen et al, , 2002. It may be that the action of lactobacilli and/or bifidobacteria is not only specific to the individual bacterial strain or species but is strongly dependent on the cell type.…”

Safety assessment of probiotics for human use

“…Although several reports of sepsis in at-risk individuals have been linked to lactobacilli, there is no conclusive evidence from analysis of clinical isolates that would indicate any species-related properties that would favor infection in atrisk populations. 14 Asahara and colleagues 137 have suggested that resistance to host innate defence mechanisms should be considered in the safety assessment of Lactobacillus strains, but research in this area is limited.…”

Inocuidad, prevención y riesgos de los probióticos

“…With this background in mind it is possible to consider bacteremia due to Lactobacillus as an index of serious defects in the immunity of those affected 3 . In episodes of bacterial endocarditis in adults, Lactobacillus appears as an etiological agent in 0.05 to 0.4% of episodes, reflecting its a limited capacity to adhere to the endothelium of undamaged heart valves, which was confirmed in experimental models 4 . In a study of 280 infants, who received one of three infant formulas containing different probiotics and prebiotics between birth and 4 months of age, there were no negative effects on their growth and development.…”