Gut Microbiota of HIV Infected Pregnant Women

Birth Outcomes in HIV

Both antiretroviral-therapy (ART)-naïve and ART-experienced HIV-infected pregnant women have higher incidences of pre-term birth (PTB) compared to HIV-uninfected women. For example, the global prevalence of PTB is around 8%, while the rates in in HIV-infected populations are as high as 25%. However, even among HIV-infected populations, other risk factors are important as HIV infection still only results in PTB among a subset of all HIV-infected pregnant women. In HIV-infected pregnant women, studies have identified low maternal CD4 count, high viral load, co-infections, co-morbidities and treatment regimen as some of the risk factors for PTB, but the role of gut microbiome has not been examined.

Gut Microbiome in HIV

HIV-infected individuals have a different gut microbiome composition (eg, lower diversity; high Prevotella) compared to HIV-uninfected individuals, with differences remaining even after antiretroviral therapy. Recent studies have only begun to determine whether these changes are associated with correlates of outcomes including inflammation. More importantly, it is not known whether differences in microbiome diversity and composition among HIV-infected individuals can explain the differences in outcomes such as HIV treatment failure. The microbiome could be especially important for HIV as it infects a disproportionate amount of CD4+ T cells from the gastrointestinal (GI) tract. Even after suppressive ART, there is irreversible damage to the GI tract affecting mucosal immunity (including incomplete reconstitution of CD4+ T cells) and gut dysbiosis. This gut dysbiosis has been proposed as one of the mechanisms that result in microbial translocation and inflammation seen in many HIV-infected individuals, factors that have been associated with PTB in HIV-infected and uninfected populations. 

Gut Microbiome in Pregnancy 

Limited studies from Western countries on the gut microbiota of pregnant women show that there are compositional changes in the microbiota between the first and third trimester of pregnancy (with one sample taken at each time) with the microbiome becoming less diverse as pregnancy progresses. A new study also conducted in Western populations, with more frequent sampling during pregnancy (2nd trimester or after), showed that the gut microbiome was relatively stable during this period. While studies have assessed the association of other types of microbiome (eg, vaginal and placental) with PTB, studies are lacking on the relationship of the maternal gut microbiome during pregnancy and PTB. 

Need for Longitudinal Gut Microbiome Studies

Most of the studies described so far, particularly the ones in HIV-infected populations, have determined the diversity and composition of the microbiome based on stool samples collected only once per individual. This approach can be problematic for epidemiologic studies because that sample might not be representative of the ‘usual’ gut microbiome. More importantly, as seen with the vaginal microbiome, there might not actually be a ‘usual’ gut microbiome for many individuals. There might be different profiles of microbiome stability (some more stable than others) where the stability itself, rather than just diversity and composition at one time point, might be a risk factor for outcomes such as PTB. This study will address a crucial first step of determining the stability of the microbiome in order to decide whether longitudinal sampling is needed in the larger association studies.

Role of Diet and Potential Interventions

Diet is the major factor influencing the gut microbiome, and we will be collecting rigorous dietary data. We will not only be able to control for diet in association studies of HIV and gestational age with microbiome stability, but novel research questions can also be answered such as determining whether there are any dietary patterns associated with microbiome stability, and whether there are differences by HIV status. Using the same food-frequency questionnaire that will be used in this study, it has been shown that the two most dominant dietary patterns in urban Mumbai, India (with population characteristics similar to ours in urban Pune) were diets high in “fruit and vegetables” followed by diets high in “snacks and meats”. More importantly, they showed that these dietary patterns were associated with cardio-metabolic risk in adults in India. Whether we observe a similar or different dietary pattern (given these patterns are determined based on data-driven factor analysis) in our study population, we will be able to determine the association of dietary patterns with outcomes (gut microbiome stability and PTB). Our study could inform future testing of interventions related to diet, probiotics, and prebiotics to modulate the gut microbiome stability in order to improve HIV outcomes in perinatal populations.

Primary Objectives

1. 
   Determine the association of gestational age with microbiome diversity among pregnant women
2. 
   Determine the association of dietary groups and patterns with microbiome diversity and stability over time
3. 
   Compare the microbiome stability between HIV-infected and uninfected pregnant women (using data from sub-study)