Are gut imbalances a risk factor for HIV infection?

HIV

The gut microbiota

Numerous studies have shown that HIV infection is associated with an imbalance of the gut microbiota (dysbiosis). Now US researchers¹ have made the surprising discovery that this dysbiosis precedes HIV infection and may even be a risk factor for the disease.

About this article

Created 24 November 2022

Updated 19 July 2024

For scientists, an “association” is where two phenomena occur at the same time, without necessarily having a cause-and-effect relationship. Is the gut dysbiosis (i.e. imbalance of the gut flora’s composition) observed in those infected with human immunodeficiency virus (HIV) a cause or a consequence of the disease? Or is it both? With only a few days to go before World AIDS Day on December 1st, the jury is still out, since the state of the gut microbiota prior to infection is not well known, and many other factors influence the appearance of dysbiosis, including age, diet, antibiotic use, and even sexual behavior, according to some recent data^2,3.

To get a clearer picture, US researchers brought together gut microbiota samples from about 50 men who have sex with men, collected during different studies. They selected individuals with similar profiles (age, ethnicity, sexual behavior, etc.), half of whom were infected with HIV during the course of the studies, with the other half remaining HIV free. They were thus able to compare the gut microbiota of the infected men before and immediately after infection, and to compare the infected men’s gut microbiota with that of the healthy uninfected pairs.

38 million At the end of 2021, approximately 38 million people were living with HIV worldwide, more than two-thirds of them in Africa.

_Sources

Minimal changes in microbiota before/after HIV infection...

The authors first found that the composition of the infected men’s gut microbiota changed very little during the acute phase of HIV. Only increased Fusobacterium mortiferum was observed. Not normally resident in the gut flora, this bacterial species had already been associated with HIV in other studies.

... but significant pre-infection differences vs. controls

In contrast, the gut microbiota of the men who would go on to be infected with HIV (i.e., their “pre-infection” gut microbiota) differed from that of the controls (who remained HIV free). In particular, they had fewer bacteria from the Bacteroides group, and increased levels of Megasphaera elsdenii, Acidaminococcus fermentans, and Helicobacter cinaedi. This type of dysbiosis has frequently been observed in HIV-infected individuals. However, in this new study, the gut imbalance appears to have been present before infection, potentially influencing susceptibility to HIV, according to the authors.

Transmission of HIV

HIV is a virus transmitted through sexual contact, through the blood, and from mother to child (during pregnancy, childbirth, or breastfeeding). It attacks cells that carry a CD4 receptor, particularly T cells, a type of white blood cell that performs a major immune function in the body’s defense against attack by external microbial agents (bacteria, viruses, or fungi) or other foreign invaders.

HIV infection occurs in three successive phases over 10 years on average (with significant differences between individuals):

The acute or primary infection phase begins 10 to 15 days after infection and lasts about two weeks. The virus invades the body, penetrates the CD4 cells, and is fought by the immune system. This stage may be asymptomatic or appear as a flu-like illness.
The chronic phase results in the exhaustion of the immune system, mainly through the progressive loss of CD4 T cells. It can last several years and may be accompanied by minor skin and gastrointestinal disorders, mild fever, night sweats, etc.
The AIDS (acquired immunodeficiency syndrome) phase corresponds to a very low level of CD4 T cells and the onset of opportunistic diseases (which “take advantage” of the weakness of the immune system to develop) such as serious infections or certain types of cancer.⁴

Gut microbiota, a new tool for preventing HIV?

So, does gut microbiota composition play a role in susceptibility to HIV infection? Encouraged by similar conclusions from another US team⁵, the researchers propose that this avenue be followed up by studies on larger samples. They hope that this will identify a “gut microbiota signature” associated with greater susceptibility to HIV infection, thus allowing more targeted prevention via treatment of the gut microbiota of people at risk.⁶

The researchers make it clear that this finding does not contradict the idea that HIV can itself cause dysbiosis. The short duration of the study meant it was not possible to observe the changes in gut microbiota composition that occur during chronic HIV. In addition, these results were obtained in a small group with a specific profile and thus generalizability beyond this population is limited.