Targeting the gut microbiota could help protect against Listeria monocytogenes infection

It is known that the gut microbiota provides colonization resistance (CR) against many infections by enteric pathogens. Although murine experimental models have been previously developed to study the underlying mechanisms of CR in the host, a better understanding is needed in order to develop new approaches for prevention of foodborne pathogen infection.

A recent study, led by Dr. Simone Becattini and Dr. Eric G. Pamer from the Memorial Sloan-Kettering Cancer Center in New York, has found that targeting the gut microbiota could improve colonization resistance against severe listeriosis.

Listeria monocytogenes is a major pathogen acquired by eating contaminated food; in immunocompetent animals and humans, ingestion of the bacterium does not usually lead to systemic disease. However, some populations such as infants, pregnant women, elderly persons, and immunocompromised cancer patients are susceptible to more severe forms of listeriosis in which the pathogen causes septicaemia, meningitis and even death.

The researchers found that treating mice with antibiotics before an oral gavage of a sublethal dose of L. monocytogenes increased the pathogen’s growth in the intestine, leading to its translocation into the circulatory system. The effect of antibiotics was even more noticeable in immunocompromised mice lacking key immune cells and these animals succumbed to even small doses of L. monocytogenes when their gut microbiota was depleted by previous antibiotic treatment. Besides this, mice treated with the chemotherapy drugs doxorubicin and cyclophosphamide became even more susceptible to listeriosis when they were also treated with antibiotics. These data show that anticancer chemotherapy and antibiotics synergistically enhance susceptibility to L. monocytogenes infection in mice.

It was also found in ex vivo experiments that commensal gut microbes mediated L. monocytogenes clearance in the absence of host-derived factors. The authors suggested that “bacteria inhabiting different intestinal regions efficiently eliminated L. monocytogenes by multiple mechanisms”.

The researchers also identified in vivo that multiple Clostridiales strains provided CR against L. monocytogenes infection. To identify which specific strains were involved, a panel of Clostridia strains from human isolates, commercially available strains and isolates from mouse stool were screened through co-culture with L. monocytogenes under anaerobic conditions. Four bacterial strains (Clostridium saccharogumia, C. ramosum, C. hathewayi, and B. producta) acted as a consortium in reducing L. monocytogenes growth in laboratory cultures. Transferring these bacteria into germ-free mice protected them from L. monocytogenes infection by limiting the pathogen’s ability to colonize the gastrointestinal tract and disseminate into other tissues.

In conclusion, the gut microbiota may have a role in protecting the host against L. monocytogenes infection based on this mouse study, and a consortium of commensal bacteria from Clostridiales seems to be involved. According to the author Simone Becattini: “Augmenting colonization resistance functions in immunocompromised patients by introducing these protective bacterial species might represent a novel clinical approach to prevent L. monocytogenes infection”.

Reference:

Becattini S, Littmann ER, Carter RA, et al. Commensal microbes provide first line defense against Listeria monocytogenes infection. J Exp Med. 2017. doi: 10.1084/jem.20170495.