Why are HIV researchers interested in the bacterial and fungal environments present in the human digestive system?

By Michael Dumiak

Our bodies are not really ourselves: at least not completely.

Trillions of bacteria, fungus, and viral organisms make their homes throughout and on the surface of the human body in a series of mini ecosystems. Scientists refer to this as the human microbiome. The creatures that live in the microbiome are the microbiota.

Researchers are particularly interested in the microbiota and the composition of the microbiome in the intestinal tract in the stomach or gut. It is there that the microbiome seems particularly lively and where researchers suspect that altering or modulating the multitude of microorganisms that live there can have either ill or beneficial effects upon the health of an individual. One simple example of modulating the quantity of microorganisms in the gut is taking probiotics, such as those in yogurt, which are the types of good bacteria that can aid digestion. Viruses, like HIV, can have a negative impact on the gut microbiome, and there may be links between the gut microbiome and other diseases as well, including Malaria.

HIV and the gut

Scientists have known for some time that HIV is first and foremost a virus associated with the gut. From the moment after it establishes initial infection, HIV wreaks havoc in the gastrointestinal tract. The virus primarily attacks immune cells known as CD4+ T cells and the majority of these cells exist in the tissues that line the gut. As HIV infects these cells, it results in inflammation. As the virus progresses and becomes a persistent, chronic presence, it disrupts the regulation of the immune system in the intestines and the mucosal barrier that lines them, allowing bacteria to escape the gut. The alterations in the gut mucosa that occur as a result of HIV infection may also affect the microbiome. In recent years researchers have linked the malfunctioning of the intestinal immune barrier to an imbalance in gut bacteria , with much more ‘bad’ bacteria being present than ‘good’ as a result. This imbalance can spark chronic inflammation and overstimulation of the immune system, one of the hallmarks of HIV and a long-term problem, even in individuals on effective therapy.

Last April the US National Institutes of Health, among others, sponsored the first HIV Microbiome Workshop, drawing more than 100 researchers and participants. A second, larger workshop will be held in November, signaling the increasing interest in studying the microbiome in the context of HIV research. This topic was also one of many discussed earlier this year at the annual Conference on Retroviruses and Opportunistic Infections.

Efforts are underway to describe and understand the gut microbiome and its apparent involvement in the progression of HIV disease. Researchers hope that one day it may even be possible to change the makeup of a person’s gut microbiome to reconstitute immune function in those living with HIV. This could reduce virus-related chronic inflammation which affects all HIV-infected individuals even if their virus levels are kept in check by antiretroviral therapy. By reducing inflammation, it would help ease some of the health burdens associated with chronic HIV infection such as heart disease, increased risk of stroke, and accelerated aging.

One such effort underway by researchers at the University of California in San Francisco (UCSF) involves fecal microbial transplantation, in which the poop containing healthy or particularly calibrated microbiota is transferred to a patient’s colon. UCSF gastroenterologist Ma Samsouk says it is possible that administration of different types of good bacteria could boost the effects of therapies aimed at curing HIV. He says it could also help restore the very damaged gastrointestinal tract of someone with HIV infection. This strategy is successful in treating another infection but it is still early days in using fecal transplantation to reverse the damage from HIV. Further research and experimentation is necessary to see if this will be a feasible approach.

Understanding the microbiome

It is an age of discovery for the microbiome, but it is also rather complicated. There are trillions of different microorganisms that reside in the gut and it is difficult to tease out exactly what is happening there. Unlike blood samples that can easily be obtained to track the progression of HIV infection, gut biopsies are harder to come by.

There are also vast differences in the microbiomes of different people as a result of geography and diet. A person growing up in the west may have very specific differences in their gut microbiome from someone in rural Africa, whose diet varies greatly.

Jesús-Mario Luévano, Jr., a medical student at Harvard Medical School and a member of Doug Kwon’s mucosal surfaces lab at the Ragon Institute of Massachussetts General Hospital, the Massachusetts Institute of Technology, and Harvard, analyzed 140 fecal samples from volunteers in Boston and 110 from Ugandan volunteers. He found a clear difference in the samples taken from Boston volunteers who were HIV infected and those uninfected. But this difference based on HIV-infection status was not evident in samples from Uganda. However there were clear differences in the composition of the microbiomes between Ugandan volunteers and those in Boston regardless of whether they were HIV infected. This variation illustrates how difficult it may be to determine precisely what effects HIV has on the microbiome.

Michael Dumiak reports on global science, technology, and public health and is based in Berlin.