Background
Children with HIV exposure (CHEU) who do not experience HIV infection are at increased risk of growth faltering compared to children unexposed to HIV (CHU). Decreased abundance of Bifidobacterium has been associated with growth faltering in CHEU. We examined the gut microbiota of CHEU versus CHU to determine if specific microbes may influence growth outcomes.
Methods
16S rRNA sequencing of the V4 region was performed on rectal swabs collected at 3 months of age as part of a prospective clinical study in Migori, Kenya. WHO Z-scores (weight-for-age [WAZ] and length-for-age [LAZ]) were calculated using weight and length measurements within 7 days of birth, at 3 and 6 weeks, and months 3, 6, 9, 12, 18 and 24. Linear mixed effects models were used to identify differentially abundant bacterial taxa between CHEU and CHU, and an interaction term was added to test whether associations between growth outcomes and bacterial abundances differed between the two groups.
Results
Rectal swabs from 319 children (164 CHEU and 155 CHU) passed all filtering and quality control steps and were used for analysis. Most children were born full term (91%) and 87% were exclusively breastfed at 3 months. All CHEU began ARV prophylaxis from birth and 98% received prophylactic cotrimoxazole from 6 weeks of age. LAZ and WAZ were lower in CHEU vs CHU (t=-1.69, p=0.09 for length; t=-2.56, p=0.01 for weight) over the first two years. HIV exposure contributed minimally to overall variation in microbiome composition (0.39%, p=0.08) at 3 months of age, and no significant differences in alpha diversity or genus-level relative abundances were observed between CHEU and CHU. In an interaction model, the association between Bifidobacterium abundance and WAZ at 3 months of age was stronger among CHEU as opposed to CHU (t=1.87, p=0.06).
Conclusions
Although growth trajectories differed between CHEU and CHU, there were no significant differences in the gut microbiome of CHEU versus CHU at three months. Bifidobacterium abundance was associated with growth outcomes in CHEU. Establishment and maintenance of infant gut Bifidobacterium populations may be of particular importance in influencing growth among CHEU.