The Microbiome in HIV

Sergio SERRANO

Hospital Ramon y Cajal
Madrid, Spain

Santiago Moreno, chef de service en maladies infectieuses

Santiago MORENO

Hospital Ramon y Cajal
Madrid, Spain

The microbiome has become a hot topic in recent years, since in recent years it has being shown that it ensures key functions for his host. These include protection against pathogens, provision of essential nutrients for the host and instruction and functionality of the immune system. Even respiration is performed by cell structures that originated from bacteria in symbiotic relationships with eukaryotic cells; the mitochondria. Hence, the microbiome has been implicated in many conditions. Infectious diseases are no exception.

It seems likely to expect that in many diseases with which the microbiota has been associated, changes in microbial communities are a consequence, rather than a cause of the disease condition. There is, however, an emerging consensus that the microbiome plays a relevant role in the pathogenesis of a number of diseases, mainly related with nutrition, metabolism, autoimmunity and cancer. Experimental studies and clinical trials aimed at shaping the microbiome will help to elucidate whether the microbiota contributes to the development of a disease or is merely an epiphenomenon of a disease.

We have become very interested in the interactions between the microbiota and mucosal immunity and the role of these in the sustainment of chronic inflammation, which drives an altered aging process in our patient population. A crucial question in the HIV field is whether abnormalities in the microbiota secondary to HIV infection contribute to this pro-inflammatory status. Hence, to provide experimental evidence, we are evaluating in HIV-infected individuals the effects on inflammation of several interventions aimed at shaping the microbiota to exert long-term benefits on gut mucosal immunity. For example, we are assessing the safety and the efficacy of repeated, low dose, fecal transplants using encapsulated stools from donors, who are selected based on their microbiome signatures.

In coming years, the microbiota might prove helpful for future HIV care. For example, the gut microbiota seems to contribute via different pathways to the extent of immune recovery during ART and correlates with inflammation – opening avenues for studies aiming to fully restore health. The interplay between the gut microbial communities and the immune system is so strong that their role in the spontaneous control of HIV infection is being investigated, with the rare population of elite controllers being interrogated. Also, the microbiota seems to affect the response of candidate vaccines against HIV. In addition, changes in the microbiota, secondary to HIV infection, could explain the increased susceptibility to tuberculosis, since this has been demonstrated to be predicted by the presence of bacteria which produce metabolites that suppress specific immune responses against Mycobacterium tuberculosis. A fascinating topic in which the microbiota is being revealed as a key player is HIV prevention.  For example, increased risk of HIV acquisition in South African women has been linked with increased cervicovaginal inflammation, which is fuelled by specific changes in the microbiota. Similarly, the protective effect of circumcision in the risk of HIV acquisition in men from women appears to be explained by changes in the penile microbiota. Finally, some bacteria have been shown to be able to catabolize antiretroviral drugs at mucosal sites, affecting drug antiretroviral levels and possibly explaining the disperse outcomes of pre-exposure prophylaxis studies.

As mentioned above, the spectrum of opportunities for the microbiota-based medicine is very broad in HIV. A great generation of HIV scientists have shifted their attention to the microbiota and I strongly believe that we will be able soon to exploit the microbiome to improve HIV care. Although we have just started to scratch the surface of the causes and consequences of the alterations in microbiota across health and disease, meaningful research with potential to change modern medicine has begun to crystallize.