Probiotics to prevent respiratory infections in the elderly

The set of microorganisms that populate the gut, called the gut microbiota, has a key role in digestive and extra-intestinal health. The lung is also populated by microorganisms that form the pulmonary microbiota. These two microbiota and their reciprocal interactions are the subject of a project led by the “Microbiota and digestive and respiratory health” team of the Institute of Food Microbiology for Health Micalis (Paris-Saclay University, AgroParisTech, INRAE). The understanding of the interactions between these microbiota and nutrition offers a ground for new innovative strategies for the prevention and treatment of respiratory infections in the elderly.

The vulnerability of the elderly to respiratory infections is a long-standing problem, exacerbated today by the health crisis. It is in this context that Muriel Thomas’ team at the Micalis Institute has been interested in recent years in pulmonary bacteria isolated in mice and which influence the immune response. These results call for further research in the field of pulmonary microbiota. Vinciane Saint-Criq, a physiologist of the pulmonary epithelium and a research fellow in the team, is currently developing a project on the impact of nutrition on respiratory infections in the elderly.

Age and aging of the lungs
Age affects the respiratory system in three main ways. The first is mechanical. The lungs become less rigid, the volume of the alveoli increases and the respiratory capacity is affected. This makes it more difficult for the elderly to evacuate particles and pathogens that would have made their way to the respiratory tract, thus increasing the risk of infections in these people.

The second impact is not specific to the lungs but corresponds to a degradation of the immune response: it is the immunosenescence. Its consequence is a fragility intrinsic to the age of the individual and a difficulty in forming a long-lasting immunity, which compromises the effectiveness of vaccines in elderly people.

Finally, age also affects the microbiota, whether in the lungs or the intestines. The levels of bacteria essential to the proper functioning of the body become unbalanced, accompanied, moreover, by an undernutrition frequently observed in the elderly.

An unexpected link
The concomitance between the disruption of the intestinal microbiota and the propensity to respiratory infections points to a potential correlation between the intestinal and respiratory systems. Intuitively, these do not seem to communicate and their respective microbiota have been studied separately. But a closer look at the human anatomy makes it possible to see more clearly.

Firstly, both devices share the same entry point, the mouth. Furthermore, when coughing out particles from the bronchi, microorganisms can pass from the lung to the intestine. The reverse is also possible, when the stomach and esophagus reflux. Finally, the lungs and intestines are involved in the transport of metabolites, small molecules resulting from metabolism that reach the bloodstream or immune cells that transit in the lymphatic circuit. “Our hypothesis is that undernutrition, the lack of certain nutrients, will generate a terrain conducive to the installation of certain respiratory infections. These studies will lead us to consider nutrition as a lever for action to prevent, or at least alleviate, the consequences of respiratory infections in the elderly,” explains Vinciane Saint-Criq.

In practice, how can this be done?
To study these mechanisms, researchers at the MICALIS Institute have several alternatives, ranging from cellular models for in vitro studies to animal models for fundamental research. In the case of more applied research, the team takes saliva samples and exploits the similarity of microbiota.

To get down into the upper respiratory tract, one technique is to have the person inhale a saline solution, induce sputum and recover the local microbiota. A more precise – but also more restrictive – technique consists of injecting physiological liquid into the lower respiratory tract and then recovering it. “This is an invasive technique. It must be performed under anesthesia and is usually done in a clinic, when the patient has pathologies that require going to see what is going on inside,” explains Vinciane Saint-Criq. Researchers sometimes recover excess material, with the patient’s consent, and use it to study the microbiota of the lower respiratory tract, the least accessible.

To obtain clinical samples or conduct more in-depth studies, the team has a network of collaborators, including physicians and clinicians, as part of its multidisciplinary approach. For example, Vinciane Saint-Criq is leading another project in collaboration with the Institut Necker-Enfants malades (INEM) and financed by the ANR (Agence nationale de la recherche). The Saint-Antoine, Bichat and Beaujon hospitals in Paris are also recurrent partners of the team. “This is a very strong link between the AP-HP and the MICALIS team located in Jouy-en-Josas.

Promising spin-offs
The team plans to build its network of industrial collaborations in a second phase. The potential spin-offs are considerable, in the pharmaceutical, nutritional and gerontological fields. Everything seems to indicate that in addition to a prevention mechanism, this research will lead to new treatments. For example, the flu is not necessarily very serious in itself, but it is the possible bacterial superinfection that it involves that makes it serious,” explains Vinciane Saint-Criq. Studies have shown that during an influenza infection, acetate levels, a metabolite produced by the intestinal microbiota and essential to its immune system, decrease. And when we supplement mice with this metabolite after their flu infection, we reduce the appearance of bacterial superinfections of the lungs. This is still a preventive measure, but that is what we want to achieve: to give probiotics and prevent the deleterious evolution of a respiratory infection.

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