About the Author(s)


Taona E. Mudhluli symbol
Department of Biochemistry, Faculty of Science, Midlands State University, Gweru, Zimbabwe

Department of Laboratory Investigative and Diagnostic Sciences, Faculty of Medicine and Health Sciences, University of Zimbabwe, Harare, Zimbabwe

Runyararo Mashingaidze-Mano symbol
School of Medicine, Faculty of Health Sciences and Veterinary Medicine, University of Namibia, Windhoek, Namibia

Inam Chitsike symbol
Department of Maternal and Child Health, Faculty of Medicine and Health Sciences, University of Zimbabwe, Harare, Zimbabwe

Justen Manasa symbol
Department of Laboratory Investigative and Diagnostic Sciences, Faculty of Medicine and Health Sciences, University of Zimbabwe, Harare, Zimbabwe

Lindsay J. Hall symbol
Department of Microbes, Infection and Microbiomes, College of Medicine and Health, University of Birmingham, Birmingham, United Kingdom

Exnevia Gomo symbol
Department of Laboratory Investigative and Diagnostic Sciences, Faculty of Medicine and Health Sciences, University of Zimbabwe, Harare, Zimbabwe

Danai T. Zhou Email symbol
Department of Laboratory Investigative and Diagnostic Sciences, Faculty of Medicine and Health Sciences, University of Zimbabwe, Harare, Zimbabwe

Citation


Mudhluli TE, Mashingaidze-Mano R, Chitsike I, et al. Gut microbiota of sub-Saharan Africa infants exposed to antiretroviral therapy: Scoping review. Afr J Prm Health Care Fam Med. 2025;17(1), a4939. https://doi.org/10.4102/phcfm.v17i1.4939

Review article

Gut microbiota of sub-Saharan Africa infants exposed to antiretroviral therapy: Scoping review

Taona E. Mudhluli, Runyararo Mashingaidze-Mano, Inam Chitsike, Justen Manasa, Lindsay J. Hall, Exnevia Gomo, Danai T. Zhou

Received: 21 Feb. 2025; Accepted: 08 Aug. 2025; Published: 29 Sept. 2025

Copyright: © 2025. The Author(s). Licensee: AOSIS.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background: Antiretroviral (ARV) exposure influences the early-life gut microbiota in regions with high human immunodeficiency virus (HIV) burdens. Understanding how ARV drugs affect the infant gut microbiota is important for optimising short-term and long-term health outcomes.

Aim: This scoping review synthesises current evidence on the gut microbiota of infants born to mothers with HIV (MWH) in sub-Saharan Africa, focusing on the effects of in utero and postnatal ARV exposure. By examining emerging data in this context, we highlight potential implications for infant health and identify key areas for future research.

Method: Online databases were systematically searched using comprehensive search strategies. In addition, grey literature was explored. Three authors independently screened titles and abstracts for relevance, evaluated full-text articles for eligibility and performed data extraction.

Results: The scoping review highlights differences in gut microbiota because of HIV exposure and ARV drugs in infants born to sub-Saharan African MWH. Of interest is a disturbance in the gut bacterial balance in infants with HIV, who harboured enriched with more diverse and potentially harmful bacteria relative to HIV-exposed uninfected infants. There was agreement from some countries, that is Nigeria and Zimbabwe, that their gut microbiota genomes comprise Bifidobacterium longum subspecies infantis and Enterococcus.

Conclusion: Both antiretroviral therapy and HIV influence the gut microbiota in infants born to MWH. Pathogenic overgrowth within the infant gut microbiota for individuals with HIV may impair immune maturation during early-life, with lasting consequences for host health.

Contribution: This highlights the need for further research into probiotic interventions for infants in high HIV-burden settings.

Keywords: antiretroviral drugs; gut microbiota; human immunodeficiency virus; infants; sub-Saharan Africa.

Introduction

In the sub-Saharan African region, the gut microbiota of more than 1.5 million infants is exposed to antiretroviral (ARV) drugs because of the high prevalence of human immunodeficiency virus (HIV).1,2 The use of ARV drugs has been a game-changer in preventing mother-to-child transmission of HIV infection (PMTCT) since the early 2000s.1,2 This strategy has significantly reduced the risk of HIV transmission from mother-to-child during pregnancy, childbirth and breastfeeding.3 The ground-breaking Paediatric AIDS Clinical Trial Group (PACTG) Study 076, conducted in 1994, marked a significant milestone in PMTCT.3 This pivotal study demonstrated the efficacy of zidovudine (ZDV) monotherapy in reducing the risk of HIV transmission from mother to child.3 Building on this success, subsequent trials explored more comprehensive regimens, combining ZDV with other ARV agents such as lamivudine (3TC), nevirapine (NVP) and protease inhibitors (PIs).3 These studies investigated various antepartum, intrapartum and postpartum treatment strategies, ultimately shaping the evolution of PMTCT guidelines and paving the way for more effective, multi-drug approaches to prevent HIV transmission and improve maternal and infant health outcomes.3 The most recent PMTCT programme, the Option B+, initiates all pregnant or breastfeeding women with HIV onto lifelong triple antiretroviral therapy (ART), regardless of their CD4 count or clinical stage, promoting better adherence and health outcomes.1,2,3 Since the introduction of PMTCT worldwide, HIV transmission rates from mothers to their children have declined from more than 25% to less than 2%.3

Recommendations by the World Health Organization for infant prophylaxis

According to current World Health Organization (WHO) guidelines, postnatal prophylaxis for infants born to mothers with HIV (MWH) typically involves administering either NVP or ZDV for 4 to 6 weeks.4 In cases where breastfeeding infants are at high risk of HIV transmission, the prophylaxis may be extended to 12 weeks.4 In the PMTCT context, ARV prophylaxis is the administration of ARV drugs to infants born to MWH.5 Despite being used by over 1.5 million infants in sub-Saharan Africa (SSA), the impact of ARVs on the body and the microbial communities within them – the microbiota – remains incompletely understood, highlighting the need for further research.6

Potential effect of different antiretroviral drugs on the human gut microbiota

The potential effect of different ARV drugs on the gut microbiota of HIV-exposed infected (HEI) and HIV-exposed uninfected (HEU) individuals has been described from in vitro experiments (Table 1),7,8 but largely overlooked in human microbiome studies. It is plausible that either HIV exposure, HIV infection or ARV drugs impact the early microbiota of infants born to MWH at an early age.1,9,10 Furthermore, in utero-HEU individuals have a higher incidence of hospitalisation and 2 to 4-fold higher mortality rate than HIV-unexposed uninfected (HUU) infants in low- and middle-income countries (LMICs).11,12,13 However, there are inconsistencies in the few published reports on infant gut microbiota from SSA. Therefore, this review will synthesise current key findings from SSA on the gut microbiota of HIV-exposed (HE) infants (born to MWH) on prolonged and short-term ART.

TABLE 1: Antiretroviral effects of relevant drugs from recent in vitro studies.
Recommendations by the World Health Organization for preventing human immunodeficiency virus mother-to-child transmission

The WHO outlines four key stages of the PMTCT of HIV cascade. These include pre-pregnancy, prenatal, intrapartum and postnatal interventions (Table 2).14 These stages are crucial for a comprehensive approach to preventing HIV transmission from mother to child. According to the current WHO guidelines, high-risk infants born to MWH should receive dual prophylaxis with daily ZDV and NVP for the first 6 weeks of life, regardless of whether they are breastfed or formula-fed.14 For breastfed infants at high-risk, including those first identified as HE during the postpartum period, prophylaxis should be continued for an additional 6 weeks, using either dual therapy (ZDV and NVP) or NVP alone.5,14 High-risk infants are defined as those born to mothers with documented HIV infection who received less than 4 weeks of ART at delivery, viral load > 1000 copies/mL in the 4 weeks before delivery (if viral load is available),13 incident HIV infection during pregnancy or breastfeeding or newly diagnosed HIV during the postpartum period, with or without a prior negative test.14 These high-risk infants require extended prophylaxis. In addition, breastfeeding infants of mothers on ART typically receive 6 weeks of daily NVP prophylaxis, while formula-fed infants usually receive 4 weeks to 6 weeks of daily NVP or twice-daily ZDV prophylaxis.14,15 Since the introduction of the ‘treat all’ approach, ART is initiated urgently among all pregnant and breastfeeding MWH, even if they are identified late in pregnancy or postpartum.14,15 For mothers who initiate ART around the time of labour and delivery (intrapartum), earlier WHO guidelines suggested administering a single dose of NVP along with tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC), in conjunction with 3-hourly administration of ZDV during labour.14,16

TABLE 2: Four main aspects of preventing mother-to-child transmission of human immunodeficiency virus cascade outlined by the World Health Organization.
The gut microbiota of infants exposed to antiretroviral drugs from sub-Saharan Africa

Some studies suggest that prolonged ART may help restore the gut microbiota of children with HIV (CWH) to a composition more similar to that of HUU children.17 A study of children and adolescents (6 years to 16 years) in Zimbabwe found that HUU participants had significantly higher species richness in their gut microbiota compared to HEI individuals.17 Notably, prolonged ART was associated with increased gut microbiota richness. However, the duration of ART did not impact beta diversity.17 The study’s findings suggest that while prolonged ART may have a positive effect on gut microbiota richness, the microbiota of HEI children on ART remains less diverse compared to HUU children.17 In contrast, other studies report a decrease in bacterial diversity after long-term ARV exposure.9,18 The impact of ARV drugs on the gut microbiota of infants in SSA is a significant area of interest, given the high prevalence of HIV in the region.2 Antiretroviral drugs are believed to disrupt the gut microbiota through their broad-spectrum antibacterial activity, which can affect the balance of gut microorganisms.7,8 In previous in vitro studies, ARV drugs such as NVP, TFV and ZDV exhibited antibacterial effects.7,8 The disruption is thought to occur through mechanisms such as deoxyribonucleic acid (DNA) chain termination, inhibition of bacterial polymerases and induction of the ‘SOS’ DNA damage response.7,8 The study’s findings highlight that certain ARV drugs can impact the composition of the human microbiota.

The current first-line treatment regimen for pregnant women with human immunodeficiency virus

The current first-line treatment regimen recommended for pregnant women with HIV is a fixed-dose combination of TDF, 3TC and dolutegravir (DTG)14,19 (Table 2). In several LMICs and SSA countries, current guidelines stipulate that all pregnant women previously exposed to ART, such as through PMTCT programmes or previous interruptions in ART, should take DTG-based ARV drug regimens.14,19 All newly-born infants born to MWH receive ART, postpartum if they are diagnosed with HIV, while those who are not infected but are exposed to HIV in utero, for example, the HEU infants, receive prophylaxis of either ZDV or NVP.14,15

The gut microbiota of human immunodeficiency virus-unexposed, uninfected infants at birth

In HUU infants, gut microbiota colonisation begins at birth or potentially even in utero, and continues to develop and mature over the first 3 years of life.20 The development of the early-life microbiome is influenced by various factors, including birth mode, maternal microbiota, diet (breast milk or formula), antibiotic exposure, medications, geographical location and environmental factors.20 The maturing microbiome plays a vital role in shaping a child’s immune system.21 Perturbations in the microbiome have been linked to various diseases,21 including infectious diseases, highlighting the importance of a balanced microbiome in overall health.21,22 The intestinal microbiota of neonates is characterised by low diversity and a relative dominance of the phyla23,24 Actinomycetota (formerly Actinobacteria) and Pseudomonadota (formerly Proteobacteria).23,24 The most abundant classes in infant stool are Bifidobacterium, Lactobacillus and Clostridia in that order.25,26 In healthy breastfed infants, the gut microbiota during the first 1000 days of life is typically dominated by ‘infant-type’ bifidobacteria, including: Bifidobacterium breve, B. bifidum, B. longum subsp. infantis, B. longum subsp. longum and B. pseudocatenulatum.21

Infant gut microbiota perturbations in human immunodeficiency virus-exposed infants

During the first 2 years of life, children are vulnerable to HIV exposure through perinatal transmission (in utero and during delivery) and postnatal transmission (through breastfeeding).23 Paediatric HIV infection can disrupt the normal balance of gut microbiota, leading to changes in its composition.23,24 Research suggests that exposure to HIV in utero can affect the gut microbiota of HEU infants, indicating a possible connection between the mother’s HIV status and the infant’s gut microbiota.1 Previous studies found that Bifidobacterium species were significantly less abundant in the gut microbiota of HEU infants during the first 6 months of life.1 Metabolites of ART drugs in breast milk have been linked to reduced levels of Bifidobacterium in infants.1 In HEI infants receiving long-term ART, the disruption to the gut microbiota may persist even when the virus is suppressed.27,28 Children with HIV tend to have a gut microbiome with lower bacterial richness, reduced diversity and altered bacterial composition compared to children without HIV.29 Differences in study findings on specific taxa altered by HIV infection may be because of variations in geographical location, age, route of HIV exposure and methodological approaches (sequencing and bioinformatics).20 Despite these differences, research consistently shows an increased abundance of bacteria linked to immune inflammation and decreased abundance of bacteria that support gut health and integrity.20 A study of perinatally infected CWH in India found an increased abundance of Segatella (formerly Prevotella), a bacterial taxon linked to increased microbial translocation (sCD14) and immune inflammation (IP-10).20

Methods

Review strategy

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-2020 updated guidelines for reporting scoping reviews were used to guide the search, select relevant studies and report study findings (Figure 1).30 The PRISMA-2020 checklist was used to ensure the inclusion of relevant information in the review. The Population, Intervention, Comparison, Outcome and Context (PICOC) mode – Table 3 was used to develop a research question regarding the association between ART exposure and HIV exposure with the gut microbiota of infants from SSA.

FIGURE 1: Results from the scoping review search.

TABLE 3: Showing the eligibility criteria as guided by the PICOC(S).
Data sources and search strategy

The following databases, CINHAL (Cumulative Index to Nursing and Allied Health Literature), Cochrane Library, PubMed CSV, Embase, MEDLINE, Open Dissertation, PsycINFO, ProQuest and PubMed were systematically searched for relevant articles without any restrictions (Figure 1). The databases were searched from inception until May 2024 using variations and combinations of the following keywords: Africa, ART, HIV, infants, microbio*, NVP, SSA and ZDV. The search strategy is in Appendix 1. Open Dissertations, ProQuest Dissertations and Theses Global were searched to identify grey literature. Lastly, a manual search of the reference lists and citations of relevant publications and reviews was conducted to identify additional studies.

Eligibility criteria and ethics
Inclusion criteria

Studies that meet the PICOC(S) framework (Table 3) were included.

Exclusion criteria

Studies were excluded if the:

  • The study population were HE at an older age than 36 months.
  • Full-text and abstract were both unavailable or only the abstract was available, but did not convey the needed data.
  • The studies were narrative, scoping or systematic reviews.
Study selection and data extraction

The Rayyan Systematic Review Management Software combined and de-duplicated articles retrieved from the searches. Two authors T.E.M. and D.T.Z. independently screened the titles and abstracts to identify articles that meet the inclusion criteria (see search strategy in Appendix 1). T.E.M. obtained full-texts of the articles that passed the first screening. D.T.Z. assessed full-text papers that were identified as potentially relevant for inclusion or exclusion. Discrepancies were resolved through discussion with a third author R.M.-M. and by consensus. Studies that met the inclusion criteria were retained for data extraction. Quality assessment was not conducted in this scoping review.

Data extraction

… and … independently extracted data from each article retained in the full-text screening using a pretested data extraction form developed by the reviewers. Any uncertainties regarding the inclusion of studies were resolved through discussion with a third author (R.M.-M.) and by consensus. The following data were extracted from each article included: (1) bibliographic information, (2) study design, year of study and location, (3) study aims or objectives, (4) study population, (5) sample size, (6) intervention, (7) comparison group, (8) outcome (diversity of gut microbiota).

Ethical considerations

This was previously published data and did not require ethical clearance. This article followed all ethical standards for research without direct contact with human or animal subjects.

Review findings

This scoping review shares findings from multiple contexts across the sub-Saharan African region (Table 4).

TABLE 4: Infant gut microbiome studies from sub- Saharan African region.
Antiretroviral drugs used in sub-Saharan Africa

Recommendations of ARV drugs in many SSA countries align with WHO guidelines.29 Though the region is multi-contextual, SSA constituted 60% of global HIV infections in 2020.39 Over two million children are thought to be living with HIV worldwide, of whom over 80% live in the SSA region.31 No wonder, over one million infants from SSA are born to MWH and are potentially exposed to ARV drugs during antepartum, intrapartum and postpartum stages.32 There is, however scarcity of published studies on the gut microbiome of infants exposed to HIV and ARV drugs from SSA. There are even fewer studies from regions outside SSA, though findings are somewhat similar.40

Original research focusing on the gut microbiota of sub-Saharan African infants exposed to antepartum, intrapartum and postpartum antiretroviral drugs
Cameroon findings

In Cameroon, in addition to NVP and azidothymidine (AZT) also known as ZDV, 3TC, abacavir (ABC) and lopinavir and ritonavir (LPV and r) are given to infants infected with HIV.29 One Cameroonian study found that children on ritonavir-boosted protease inhibitor (PI and r)-based ART had lower alpha diversity and altered gut microbiota composition compared to children on NVP and those uninfected with HIV.29 The gut microbiome of children born with HIV was largely characterised by a depletion of Segatella and Clostridia.29 Since the CWH were receiving both ART and prophylactic co-trimoxazole, it’s challenging to determine the individual impact of each medication on gut microbial diversity.29 A decrease in Segatella may indicate reduced fibre fermentation capacity, which can result in poorer gut health and lower production of short-chain fatty acids (SCFAs). The SCFAs – acetate, propionate and butyrate – are key mediators of gut microbiome benefits.41 They maintain gut integrity, support immune function and regulate host metabolism.41 While increased SCFA production is associated with health benefits, most evidence comes from animal studies, with limited data from well-controlled human trials.39 In addition, a reduction in Clostridia may suggest an imbalance in the microbiome, potentially increasing susceptibility to infections or inflammatory conditions.29

In another Cameroon study conducted among 80 infants (41%) were HEI, 15 (18.8%) were HEU and 32 (40%) were HUU.31 Of the 33 HEI infants, 32 (97%) were on ARV treatment. A statistically significant difference was observed between the number of HEI versus HEU infants harbouring Clostridium, Enterococcus, Klebsiella, Shigella, Staphylococcus aureus (S. aureus) and Streptococcus.31 The gut bacteria of HEI infants showed an imbalance, with a higher presence of opportunistic and pathogenic bacteria compared to HEU infants. The most common bacteria found in HEI infants were Lactobacillus, Streptococcus and Bifidobacterium. In HUU infants, E. coli, Lactobacillus and Bifidobacterium were most common. Some bacteria were notably absent in each group, for example, Actinomycetes, and Enterobacter were missing in HEI infants, as were Acinetobacter, Proteus and S. aureus in HUU infants.31

Mozambican findings

One study from Mozambique reported on the faecal microbiota of apparently healthy African infants from a community with a high HIV prevalence.32 A total of 120 faecal samples were collected. Four mothers reported taking medications at the time of the study, including amoxicillin, paracetamol, co-trimoxazole and antihypertensive drugs. Approximately 38% of infants aged < 6 months were exclusively breastfed.32 Twenty-nine MWH had detectable virus. Streptococci, Enterococci and Bifidobacteria were detected in all samples analysed, while Staphylococcus was the bacterial group least detected. The study found commonly detected bacteria such as Streptococcus, Enterococcus and Bifidobacterium, and the least detected Staphylococcus. Bacterial counts changed with infant age. Bifidobacterium, Bacteroides, Enterococcus, Clostridium leptum and Clostridium coccoides counts increased with infant’s age32 whereas Staphylococcus aureus and Streptococcus epidermidis counts were significantly reduced in older infants.32

Nigerian findings

A 2022 study in Nigeria showed marked differences in nutritional and microbiota diversity between HEU and HUU infants.1 In the study, HEU infants consistently exhibited lower weight-for-age z-score (WAZ) compared to HUU infants across all measured time points.1 At 6 months postpartum, a significant observation was made regarding the relative abundance of Bifidobacterium in HEU infants,1 which was found to be lower than that in HUU infants.1 It was noted that NVP and 3TC were present in the breast milk of MWH.1 Bifidobacterium provides numerous health benefits, including supporting digestive health, enhancing immune function, producing essential nutrients, preventing chronic diseases, aiding infant development and influencing mental health.40,42,43,44,45

Another study compared the gut microbiota of HEU and HUU infants born to 278 mothers with or without HIV, from Nigeria and South Africa.33 All 212 MWH received ART according to local guidelines, and their infants received NVP post-exposure prophylaxis after birth.33 The gut microbiota of Nigerian infants was primarily dominated by Bifidobacterium longum subspecies infantis and the Firmicutes, including both Staphylococcus species33 (e.g. S. haemolyticus, S. saprophyticus) and Enterococcus species (e.g. E. faecalis, E. faecium).33 In South African infants, certain bacterial taxa were linked to HIV exposure. Notably, several Enterococcus species were more abundant in HEU infants compared to HUU infants at week 1.45 In South African infants, the gut microbiota typically consisted of Bifidobacterium species45 (B. longum, B. catenulatum, B. breve), Firmicutes (Streptococcus species: S. salivarius, S. caprae, S. lutetiensis) and Pseudomonadota (mainly Escherichia coli).33 Pathobionts were more abundant in HEU infants during the first 15 weeks of life in the South African cohort.45 In contrast, no bacterial taxa were differentially abundant by HIV exposure in the Nigerian cohort.33

South African findings

One other South Africa-based study focused on the oral microbiome of school-aged CWH on ART.11 A few other studies in South Africa indicated great discrepancies in the interplay of the gut microbiota in HE infants.34

Another South African study analysing meconium and tracking infant faecal bacteria over time (birth to 20-28 weeks) found that in HIV-unexposed infants, Pseudomonadota (formerly Proteobacteria) decreased with age, and Clostridia increased with age.11 The impact of infant age on faecal bacterial profiles was less pronounced in HE infants.11 Higher levels of Pseudomonadota during infancy may correlate with slower growth trajectories and could predispose infants to metabolic disorders, such as obesity and insulin resistance later.46 Clostridia are known to be involved in the fermentation of dietary fibres and the production of SCFAs, such as butyrate.47 Short-chain fatty acids benefit gut health by providing energy to colon cells, maintaining intestinal barrier function and reducing inflammation.47 An increase in Clostridia may lead to higher SCFA levels, contributing to improved gut health and potentially reducing the risk of gastro-intestinal diseases.48 Therefore, the effect of infant age on stool microbiota among HE infants was less pronounced. This may imply that exposure to HIV or ART alters the typical developmental trajectory of the gut microbiome, leading to different patterns in bacterial composition as these infants age, which has implications for growth, metabolic disorders and gut health.

A South African study found that at 6 weeks, HEU infants had a higher abundance of Firmicutes, Carnobacteriaceae and Enterococcaceae compared to HUU infants.11 Conversely, it showed a lower abundance of the Coriobacteriaceae, and Bacteroidetes families, and a reduced abundance of the Pseudomonadota phylum,11 suggesting that the gut microbiome of HEU infants may be adapting differently compared to their HUU counterparts. Firmicutes are often associated with beneficial metabolic functions, including energy harvest from dietary fibres.39,49,50 The lower abundance of Coriobacteriaceae and Bacteroidetes in HEU infants could imply a potential disruption in the diversity and functionality of the gut microbiome.51,52 Bacteroidetes are generally linked to a healthy gut environment and play roles in breaking down complex carbohydrates.51,52

A 2016 South African study used shotgun metagenomic sequencing to analyse the gut microbiota of 4-week-old infants, comparing HUU neonates and HEU neonates before starting co-trimoxazole prophylaxis in the HEU group.34 There was no difference in microbial alpha diversity between HUU and HEU neonates.34 Forty-three bacterial taxa were found to be significantly differentially abundant between HUU and HEU.34 Compared to HUU neonates, HEU neonates had higher levels of pathobionts34 (Shigella flexneri, Shigella boydii and Klebsiella pneumonia) and other taxa, that is, Blautia liquoris, Coprococcus eutactus and Roseburia hominis.34 In contrast, HUU neonates had higher levels of Bifidobacterium breve, Actinomyces fecalis, Eggertella lenta and Phascolarctobacterium spp.34

Random forest analysis identified key metabolic pathways that distinguished HEU infants, with elevated levels of glycogen degradation, L-arginine degradation, L-methionine and L-rhamnose biosynthesis.34 Other pathways associated with HEU status were inosine-5-phosphate biosynthesis, lactose and galactose degradation and mixed acid fermentation.34 In HUU infants, the following pathways were elevated: pentose phosphate pathway, phospholipid biosynthesis and nitrate reduction pathway.34 The study found no significant impact of in utero HIV exposure on microbial diversity in infants at 4 weeks of age.34 However, after birth, HIV exposure alters gut bacterial microbiota composition, with HEU neonates displaying a higher abundance of pathobionts compared to HUU neonates.34 Human immunodeficiency virus exposure also seems to impact the functional metagenome in these neonates.34

A 2020 study compared the innate response and the stool microbiome of 2-year-old HEU and HUU children from Belgium, Canada and South Africa.35 The study reported no universal immune or microbiome signature underlying differences between HEU versus HUU that was applicable to all children.35 However, population-specific differences in stool microbiomes were readily detected. South African HEU and HUU children differed for WAZ,35 and differences in height-for-age z-scores (HAZ) approached significance.35 In this study, MWH formula-fed their infants to prevent transmission, while HUU infants were breastfed.35 According to the study findings, HIV exposure had a minimal impact on gut microbiota in South African children. However, differential abundance was observed for Rikenellaceae, more abundant in HEU and Succinivibrio, more abundant in HUU children.35 The authors hypothesise that breast versus formula feeding may have contributed to microbiome differences between HEU and HUU children in their study.35

A 2022 poster presentation reported findings from South Africa.36 The South African study compared 79 infants with intrauterine HIV infection (49% female), starting ART within 48 h or around 6 days of birth and 71 uninfected infants (52% female), born to MWH, receiving standard prophylaxis.36 The study collected rectal swabs at 4 weeks, 12 weeks and 24 weeks, analysing the microbiome through 16S ribosomal ribonucleic acid (rRNA) gene sequencing (V4 region).36 Human immunodeficiency virus infection was linked to notable changes in gut microbiota, with increased abundance of Bacteroides, Fusobacterium and Finegoldia, after accounting for other influencing factors.36 Other key factors influencing infant microbiome development were HIV status, age at sampling, mode of delivery, breastfeeding and sex.35 The study found that breastfeeding, combined with early ART, helped maintain a Bifidobacterium-rich microbiota profile in infants with HIV.36

Zimbabwe findings

Human immunodeficiency virus-exposed infants in Zimbabwe are exposed to one or more of the following ARV drugs: DTG, NVP, FTC, 3TC, TDF and AZT. A study described the composition of gut microbiota of children and adolescents, aged 6 to 16 years,17 with perinatal HIV infection taking ART in Zimbabwe.17 The study reported findings from 177 HEI and 106 HUU participants.17

Key findings showed that 89% of HEIs were on co-trimoxazole prophylaxis and that recent antibiotic use did not alter the impact of HIV status on species richness.17 Compared to HUU, HEI had a lower abundance of Epsilonbacteraeota and Bacteroidetes (phylum level)17 and enrichment of Corynebacterium, Lawsonella, Collinsella (Actinomycetota phylum), Finegoldia, Anaerococcus, Erysipelotrichaceae, Lachnoclostridium (Firmicutes phylum).17 Human immunodeficiency virus-unexposed uninfected participants, compared to HEI were enriched in Campylobacter,17 phylum Epsilonbacteraeota; Porphyromonas and Prevotella, phylum Bacteroidetes.17 There was also enrichment in the Fastidiosipila, Fournierella, Eubacterium coprostanoligenes_group, Ruminococcaceae, Coprococcus and Murdochiella (Firmicutes).17 Long-term ART (≥ 10 years) was associated with a more diverse gut microbiota in children, similar to that of HUU children, potentially minimising microbiota differences between HEI and HUU children.17

Another Zimbabwean study found no significant differences in gut microbiota diversity between HEU and HUU infants, as measured by alpha diversity indices (Shannon and Simpson) and stool microbial composition.37

A 2024 study reported on the infant gut microbiota members isolated from the stool of 6-week-old neonates from Zimbabwe.53 The study provided preliminary insights into the genomic makeup of specific strains of Bifidobacterium and Enterococcus recovered from an infant cohort from Zimbabwe,53 and explored some of the properties that allow these organisms to thrive in the infant gut environment.53 The final dataset comprised 6 type strain genomes representative of infant-associated Bifidobacterium and Enterococcus species53 – Bifidobacterium longum subsp. infantis, Bifidobacterium longum subsp. longum, Bifidobacterium breve, Bifidobacterium pseudocatenulatum, Enterococcus faecium and Enterococcus faecalis.53

Common Metagenomics techniques in sub-Saharan African studies

Several metagenomics techniques can be employed to investigate the gut microbiota of HE infants in Africa.14 These include the 16S rRNA gene sequencing, shotgun sequencing and whole genome sequencing of cultured isolates.6 Most of the sub-Saharan African studies utilised 16S rRNA amplification, which has limited ability to discriminate species or strain level information, nor to predict microbial function.1 The reason for selecting the 16S rRNA gene amplicon sequencing method could be mainly because of its low cost, although none of the authors specified this. Several Sub-Saharan African studies assessed the gut microbiota in infants with variable results, likely because of different HIV exposure status,1 antibiotic usage, different age groups, a range of sample sizes, different modes of feeding (exclusive breastfeeding vs. formula)1 or cohorts from different geographical areas, all of which may impact results.1

Overall summary of findings

There is still controversy amid the scarcity of data in the context of HIV or ART from the sub-region: 12 articles studied the effects of HIV and different ARV prophylaxis drugs on the gut microbiome of less than 1800 infants of varying age groups, from SSA.12 The 12 studies reported here focused mainly on breastfed infants (with some exclusively breastfed and some on mixed feeds). A few (less than 50%) of the studies followed up infants from birth to over 12 months. Using rRNA gene amplicon sequencing methods, the studies seem to disagree about whether there are differences in alpha and beta diversity of gut microbiota between the HE and HU infants from SSA. Those studies that delved deeper using shotgun metagenomics report differences in certain phyla, genus and even strains of important bacteria such as Bifidobacterium. The heterogeneity of age groups, feeding methods and maternal HIV status makes it difficult to make definitive conclusions. What we found clear is that more in-depth studies, using shotgun sequencing, whole genome sequencing in larger cohorts, followed by randomised clinical trials, are more appropriate in this context.

Limitations and strengths of the study

Though this multi-context study has limitations inherent in such studies, this scoping review facilitates understanding of how the impact of HIV and/or ART on infant microbiota differ across different Sub-Saharan African contexts.54 The scoping review also helped us identify gaps in several contexts. Its findings will benefit from further preliminary studies or primary research in local contexts. Single-context research in different Sub-Saharan African countries will be necessary to corroborate findings from this multi-context review. Most studies reported in this scoping review used 16S rRNA gene amplification methods, despite their limitations in species or strain level resolution and prediction of microbial function. The reasons for the choice of methods are not specified, though low cost could be a contributing factor. The low resolution of the bacterial phylum and genus may contribute to the variability in findings.

Implications and recommendations

Though findings are still controversial, the reviewed studies demonstrate that ART exposure can significantly alter the gut microbiota composition and diversity in HE infants and infants with HIV.35 The reported alterations, including decreased bacterial diversity and increased Proteobacteria, particularly Enterobacteriaceae abundance, may have implications for immune system development and long-term health outcomes.29,47,48,52,55 The microbial imbalance is likely shaped by multiple early-life exposures, including maternal HIV infection, ART, altered breastfeeding practices, increased antibiotic use and heightened perinatal immune activation. From a pathophysiological standpoint, reduced bacterial diversity limits the spectrum of microbial-associated molecular patterns available to prime and regulate the infant’s developing immune system. This impairs the balanced maturation of gut-associated lymphoid tissue, skewing immune development toward a pro-inflammatory state and reducing the induction of immune tolerance via regulatory T cells (Tregs). Biochemically, the over-representation of Pseudomonadota (formerly Proteobacteria) contributes to a more inflammatory gut environment. Many Pseudomonadota, such as Escherichia coli and other Enterobacteriaceae, possess highly immunostimulatory lipopolysaccharide structures that potently activate Toll-like receptor 4 (TLR4) on intestinal epithelial cells46 and innate immune cells.29,38,51 This results in upregulation of pro-inflammatory cytokines such as interleukin 6 (IL-6), tumor necrosis factor (TNF)-α and interleukin-1 beta (IL-1β),41 perpetuating mucosal inflammation and compromising epithelial barrier integrity. In addition, HIV-associated immune activation, in infants with HIV, may enhance gut epithelial oxygenation and nitrate production, favouring Pseudomonadota expansion through anaerobic-to-aerobic metabolic shifts.47,48,52 According to some of the studies in this scoping review, the gut environment of HE infants is likely to experience a decrease in obligate anaerobes, such as Bifidobacterium and Faecalibacterium, which are critical for producing SCFAs such as butyrate and acetate. Short-chain fatty acids are key epigenetic and immunomodulatory metabolites that promote Treg differentiation, support intestinal barrier function and suppress excessive inflammatory signalling.29,47,48,52,55 Their depletion in infants on ART impairs these protective mechanisms and may predispose them to long-term health consequences, including increased susceptibility to infections, allergic disorders, growth faltering and potentially metabolic or autoimmune diseases later in life.29,47,48,52,55

Thus, the combination of microbial immaturity, low diversity and Pseudomonadota-dominant microbial disturbances in infants on ART represents a biologically significant disruption of early-life gut-immune cross-talk with potential lifelong health implications. These observations must be explored in well-defined and comprehensive cohort studies with comparative groups of similar age and feeding characteristics.29,47,48,52,55

Conclusion

There is a high burden of HIV in women of childbearing age, hence it is crucial to carry out studies focusing on the composition of both gut bacteria and non-bacterial components of the microbiota, such as fungi, viruses or bacteriophages. An interrogation of whether ARV drugs have a more pronounced impact on non-bacterial microbiota is worth exploring. Future studies are also required to screen antibiotics for their impact on the various gut bacteria in the Sub-Saharan African setting. Such research will inform the design of next-generation interventions, including prebiotics and probiotics tailored for infants from SSA.

A clinical trial in adults living with HIV, reported that the Bacteroidales : Clostridiales ratio was inversely correlated with HIV reservoir size and viral control post-analytical ART interruption,20 highlighting the potential contribution of the microbiome of an individual on their HIV persistence status.20 Whether this HIV-induced modulation of the gut microbiome creates an immune environment that provides a competitive advantage for reduction of a stable HIV reservoir needs further investigation, in light of HIV cure efforts.38

Acknowledgements

Competing interests

The authors reported that T.E.M. received funding from National Institutes of Health (NIH) Fogarty International Centre Grant # D43TW010313, awarded to the University of Buffalo, SUNY, United States (US), and the University of Zimbabwe’s HIV Research Training Program. L.J.H. is supported by Wellcome Trust Investigator Award 220876/Z/20/Z; and a Biotechnology and Biological Sciences Research Council (BBSRC) Institute Strategic Programme, Food Microbiome and Health BB/X011054/1 and its constituent project BBS/E/QU/230001B to L.J.H. D.T.Z. was funded by the Africa Research Excellence Fund, United Kingdom (UK) Grant, Number AREF-312-ZHOU-F-C0880, and the NIH’s Fogarty International Center, US, awarded to the Biomedical Research and Training Institute, Zimbabwe (grant number 1D43TW011326). D.T.Z. was supported through the sub-Saharan African Network for TB/HIV Research Excellence (SANTHE), a DELTAS Africa Initiative [grant # DEL-15-006]. The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS)’s Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa’s Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust [grant # 107752/Z/15/Z] and the United Kingdom (UK) government.

The views expressed in this publication are those of the authors and not necessarily those of AAS, NEPAD Agency, Wellcome Trust or the UK government, which may be affected by the research reported in the enclosed publication. The author has disclosed those interests fully and has implemented an approved plan for managing any potential conflicts arising from their involvement. The terms of these funding arrangements have been reviewed and approved by the affiliated university in accordance with its policy on objectivity in research.

Authors’ contributions

T.E.M. made substantial contributions to the:

  • conception or design of the work; the acquisition, analysis or interpretation of data for the work
  • drafting of the work and reviewing it critically for important intellectual content
  • giving final approval of the version to be published
  • making an agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

R.M.-M. made substantial contributions to the:

  • the acquisition, analysis and interpretation of data for the work
  • reviewing the draft critically for important intellectual content
  • giving final approval of the version to be published
  • making an agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

I.C. made substantial contributions to the:

  • interpretation of data for the work
  • reviewing the draft critically for important intellectual content
  • giving final approval of the version to be published
  • making an agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

J.M. made substantial contributions to the:

  • interpretation of data for the work
  • reviewing the draft critically for important intellectual content
  • giving final approval of the version to be published
  • making an agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

L.J.H. made substantial contributions to the:

  • conception or design of the work; interpretation of data for the work
  • reviewing the draft critically for important intellectual content
  • giving final approval of the version to be published
  • making an agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

E.G. made substantial contributions to the:

  • interpretation of data for the work
  • reviewing the work critically for important intellectual content
  • giving final approval of the version to be published
  • making an agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

D.T.Z. made substantial contributions to the:

  • conception or design of the work; the acquisition, analysis and interpretation of data for the work
  • drafting of the work and reviewing it critically for important intellectual content
  • giving final approval of the version to be published
  • making an agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Funding information

T.E.M. was funded by NIH Fogarty International Center Grant # D43TW010313, awarded to the University of Buffalo, SUNY, US, and the University of Zimbabwe’s HIV Research Training Program. L.J.H. is supported by Wellcome Trust Investigator Award 220876/Z/20/Z; and a BBSRC Institute Strategic Programme Food Microbiome and Health BB/X011054/1 and its constituent project BBS/E/QU/230001B to L.J.H. D.T.Z. was funded by the Africa Research Excellence Fund, UK Grant, Number AREF-312-ZHOU-F-C0880, and the NIH’s Fogarty International Center, US, awarded to the Biomedical Research and Training Institute, Zimbabwe (grant number 1D43TW011326). D.T.Z. was supported through the sub-Saharan African Network for TB/HIV Research Excellence (SANTHE), a DELTAS Africa Initiative [grant # DEL-15-006]. The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS)’s Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa’s Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust [grant # 107752/Z/15/Z] and the UK government.

The views expressed in this publication are those of the authors and not necessarily those of AAS, NEPAD Agency, Wellcome Trust or the UK government. The authors report no other conflicts of interest in this work.

Data availability

Data supporting the findings of this study are available from the corresponding author, D.T.Z., upon request.

Disclaimer

The views and opinions expressed in this article are those of the authors and are the product of professional research. The article does not necessarily reflect the official policy or position of any affiliated institution, funder, agency or the publisher. The authors are responsible for this article’s results, findings and content.

References

  1. Grant-Beurmann S, Jumare J, Ndembi N, et al. Dynamics of the infant gut microbiota in the first 18 months of life: The impact of maternal HIV infection and breastfeeding. Microbiome. 2022;10(1):61. https://doi.org/10.1186/s40168-022-01230-1
  2. Rosenberg NE, Shook-Sa BE, Liu M, et al. Adult HIV-1 incidence across 15 high-burden countries in sub-Saharan Africa from 2015 to 2019: A pooled analysis of nationally representative data. Lancet HIV. 2023;10(3):e175–e185. https://doi.org/10.1016/S2352-3018(22)00328-9
  3. Ciaranello AL, Seage GR, 3rd, Freedberg KA, Weinstein MC, Lockman S, Walensky RP. Antiretroviral drugs for preventing mother-to-child transmission of HIV in sub-Saharan Africa: Balancing efficacy and infant toxicity. AIDS. 2008;22(17):2359–2369. https://doi.org/10.1097/QAD.0b013e3283189bd7
  4. Takah NF, Atem JA, Aminde LN, Malisheni M, Murewenhema G. Male partner involvement in increasing the uptake of infant antiretroviral prophylaxis/treatment in sub Saharan Africa: A systematic review and meta-analysis. BMC Public Health. 2018;18(1):249. https://doi.org/10.1186/s12889-018-5171-9
  5. Namara-Lugolobi E, Namukwaya Z, Owor M, et al. Twenty years of prevention of mother to child HIV transmission: Research to implementation at a national referral hospital in Uganda. Afr Health Sci. 2022;22(Spec Issue):22–33. https://doi.org/10.4314/ahs.v22i2.5S
  6. World Health Organization. HIV and AIDS fact sheet [homepage on the Internet]. 2024 [cited 2024 Nov 14]. Available from: https://www.who.int/news-room/fact-sheets/detail/hiv-aids
  7. Ray S, Narayanan A, Giske CG, Neogi U, Sönnerborg A, Nowak P. Altered gut microbiome under antiretroviral therapy: Impact of efavirenz and zidovudine. ACS Infect Dis. 2020;7(5):1104–1115. https://doi.org/10.1021/acsinfecdis.0c00536
  8. Rubio-Garcia E, Ferrando N, Martin N, et al. In vitro antibacterial activity of antiretroviral drugs on key commensal bacteria from the human microbiota. Front Cell Infect Microbiol. 2024;13:1306430. https://doi.org/10.3389/fcimb.2023.1306430
  9. Imahashi M, Ode H, Kobayashi A, et al. Impact of long-term antiretroviral therapy on gut and oral microbiotas in HIV-1-infected patients. Sci Rep. 2021;11(1):1–10. https://doi.org/10.1038/s41598-020-80247-8
  10. Shilaih M, Angst DC, Marzel A, Bonhoeffer S, Günthard HF, Kouyos RD. Antibacterial effects of antiretrovirals, potential implications for microbiome studies in HIV. Antivir Ther. 2018;23(1):91–94. https://doi.org/10.3851/IMP3173
  11. Jackson CL, Frank DN, Robertson CE, et al. Evolution of the gut microbiome in HIV-exposed uninfected and unexposed infants during the first year of life. mBio. 2022;13(5):e0122922. https://doi.org/10.1128/mbio.01229-22
  12. Anderson K, Kalk E, Madlala HP, et al. Increased infectious-cause hospitalization among infants who are HIV-exposed uninfected compared with HIV-unexposed. AIDS. 2021;35(14):2327–2339. https://doi.org/10.1097/QAD.0000000000003039
  13. Slogrove A, Reikie B, Naidoo S, et al. HIV-exposed uninfected infants are at increased risk for severe infections in the first year of life. J Trop Pediatr. 2012;58(6):505–508. https://doi.org/10.1093/tropej/fms019
  14. World Health Organization. Consolidated guidelines on HIV prevention, testing, treatment, service delivery and monitoring: Recommendations for a public health approach. WHO Team-Global HIV, Hepatitis and STIs Programmes (HHS), Guidelines Review Committee, SEARO Regional Office for the South East Asia (RGO); 2021.
  15. Njom NAE. Mother-to-child transmission of HIV through breastfeeding improving awareness and education: A short narrative review. Int J Womens Health. 2022;14:697–703. https://doi.org/10.2147/IJWH.S330715
  16. Wessels J, Sherman G, Bamford L, et al. The updated South African national guideline for the prevention of mother to child transmission of communicable infections. South Afr J HIV Med. 2020;21(1): 1079. https://doi.org/10.4102/sajhivmed.v21i1.1079
  17. Flygel TT, Sovershaeva E, Claassen-Weitz S, et al. Composition of gut microbiota of children and adolescents with perinatal human immunodeficiency virus infection taking antiretroviral therapy in Zimbabwe. J Infect Dis. 2020;221(3):483–492. https://doi.org/10.1093/infdis/jiz473
  18. Nowak P, Troseid M, Avershina E, et al. Gut microbiota diversity predicts immune status in HIV-1 infection. AIDS. 2015;29(18):2409–2418. https://doi.org/10.1097/QAD.0000000000000869
  19. World Health Organization. Update of recommendations on first- and second-line antiretroviral regimens. Geneva: WHO Team HIV/AIDS (HIV); 2019.
  20. Soo N, Farinre O, Chahroudi A, Boliar S, Goswami R. A gut check: Understanding the interplay of the gastrointestinal microbiome and the developing immune system towards the goal of pediatric HIV remission. Retrovirology. 2024;21(1):15. https://doi.org/10.1186/s12977-024-00648-9
  21. Lin C, Lin Y, Zhang H, et al. Intestinal ‘infant-type’ bifidobacteria mediate immune system development in the first 1000 days of life. Nutrients. 2022;14(7): 1498. https://doi.org/10.3390/nu14071498
  22. Maciel-Fiuza MF, Muller GC, Campos DMS, et al. Role of gut microbiota in infectious and inflammatory diseases. Front Microbiol. 2023;14:1098386. https://doi.org/10.3389/fmicb.2023.1098386
  23. RodrÍguez JM, Murphy K, Catherine Stanton C, et al. The composition of the gut microbiota throughout life, with an emphasis on early life. Microb Ecol Health Dis. 2015;26:26050. https://doi.org/10.3402/mehd.v26.26050
  24. Nguyen QT, Ishizaki A, Bi X, et al. Alterations in children’s sub-dominant gut microbiota by HIV infection and anti-retroviral therapy. PLoS One. 2021;16(10):e0258226. https://doi.org/10.1371/journal.pone.0258226
  25. Turroni F, Peano C, Pass DA, et al. Diversity of bifidobacteria within the infant gut microbiota. PLoS One. 2012;7(5):e36957. https://doi.org/10.1371/journal.pone.0036957
  26. Chakravorty S, Helb D, Burday M, Connell N, Alland D. A detailed analysis of 16S ribosomal RNA gene segments for the diagnosis of pathogenic bacteria. J Microbiol Methods. 2007;69(2):330–339. https://doi.org/10.1016/j.mimet.2007.02.005
  27. Russo E, Nannini G, Sterrantino G, et al. Effects of viremia and CD4 recovery on gut ‘microbiome-immunity’ axis in treatment-naïve HIV-1-infected patients undergoing antiretroviral therapy. World J Gastroenterol. 2022;28(6):635–652. https://doi.org/10.3748/wjg.v28.i6.635
  28. Ancona G, Merlini E, Tincati C, et al. Long-term suppressive cART is not sufficient to restore intestinal permeability and gut microbiota compositional changes. Front Immunol. 2021;12:639291. https://doi.org/10.3389/fimmu.2021.639291
  29. Abange WB, Martin C, Nanfack AJ, et al. Alteration of the gut fecal microbiome in children living with HIV on antiretroviral therapy in Yaounde, Cameroon. Sci Rep. 2021;11(1): 7666. https://doi.org/10.1038/s41598-021-87368-8
  30. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. https://doi.org/10.1136/bmj.n71
  31. Blaak EE, Canfora EE, Theis S, et al. Short chain fatty acids in human gut and metabolic health. Benef Microbes. 2020;11(5):411–455. https://doi.org/10.3920/BM2020.0057
  32. Nkenfou CN, Abange WB, Gonsu HK, et al. Evaluation of the effect of HIV virus on the digestive flora of infected versus non infected infants. Pan Afr Med J. 2019;34:24. https://doi.org/10.11604/pamj.2019.34.24.15039
  33. Iwase SC, Osawe S, Happel A, et al. Longitudinal gut microbiota composition of South African and Nigerian infants in relation to tetanus vaccine responses. Microbiol Spectr. 2024;12:e0319023. https://doi.org/10.1128/spectrum.03190-23
  34. Byrne A, Diener C, Brown BP et al. Neonates exposed to HIV but uninfected exhibit an altered gut microbiota and inflammation associated with impaired breast milk antibody function. Microbiome. 2024;12(1):261. https://doi.org/10.1186/s40168-024-01973-z
  35. Amenyogbe N, Dimitriu P, Cho P, et al. Innate immune responses and gut microbiomes distinguish HIV-exposed from HIV-unexposed children in a population-specific manner. J Immunol. 2020;205(10):2618–2628. https://doi.org/10.4049/jimmunol.2000040
  36. Kuhn L, Li F, Strehlau R, et al. Early antiretroviral therapy in neonates and maturation of the gut microbiome [homepage on the Internet]. 2022 [cited 2025 Jan 12]. Available from: https://www.croiconference.org/wp-content/uploads/sites/2/posters/2022/CROI2022_Poster_715.pdf
  37. Munjoma PT, Mazhandu AJ, Wyss JSB, et al. Characterization of the gut microbiota and systemic inflammation in HIV-exposed uninfected infants from a resource-limited setting at 6 weeks of age. Microb Health Dis. 2024;6:e1156.
  38. Mudhluli TE, Kujawska M, Mueller J, et al., Exploring the genomic traits of infant-associated microbiota members from a Zimbabwean cohort. BMC Genomics. 2024;25(1):718. https://doi.org/10.1186/s12864-024-10618-2
  39. Fusco W, Lorenzo MB, Cintoni M, et al. Short-chain fatty-acid-producing bacteria: Key components of the human gut microbiota. Nutrients. 2023;15(9): 2211. https://doi.org/10.3390/nu15092211
  40. González R, Maldonado A, Martín V, et al. Breast milk and gut microbiota in African mothers and infants from an area of high HIV prevalence. PLoS One. 2013;8(11):e80299. https://doi.org/10.1371/journal.pone.0080299
  41. Pinto-Cardoso S, Klatt NR, Reyes-Terán G. Impact of antiretroviral drugs on the microbiome: Unknown answers to important questions. Curr Opin HIV AIDS. 2018;13(1):53–60. https://doi.org/10.1097/COH.0000000000000428
  42. Kujawska M, Neuhaus K, Huptas C, et al. Exploring the potential probiotic properties of Bifidobacterium breve DSM 32583 – A novel strain isolated from human milk. Probiotics & Antimicro. Prot. 2024;2024:1–15. https://doi.org/10.1007/s12602-024-10346-9
  43. Dalby MJ, Kiu R, Serghiou IR, et al. Faecal microbiota and cytokine profiles of rural Cambodian infants linked to diet and diarrhoeal episodes. NPJ Biofilms Microbiomes. 2024;10(1):85. https://doi.org/10.1038/s41522-024-00562-0
  44. O’Callaghan A, Van Sinderen D. Bifidobacteria and their role as members of the human gut microbiota. Front Microbiol. 2016;7:925. https://doi.org/10.3389/fmicb.2016.00925
  45. Chen J, Chen X, Ho CL. Recent development of probiotic bifidobacteria for treating human diseases. Front Bioeng Biotechnol. 2021;9:770248. https://doi.org/10.3389/fbioe.2021.770248
  46. Korpela K, Zijlmans MA, Kuitunen M, et al. Childhood BMI in relation to microbiota in infancy and lifetime antibiotic use. Microbiome. 2017;5(1):26. https://doi.org/10.1186/s40168-017-0245-y
  47. Rendina DN, Lubach GR, Lyte M, et al. Proteobacteria abundance during nursing predicts physical growth and brain volume at one year of age in young rhesus monkeys. FASEB J. 2021;35(6):e21682. https://doi.org/10.1096/fj.202002162R
  48. Den Besten G, Van Eunen K, Groen AK, Venema K, Reijngoud D-J, Bakker BM. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J Lipid Res. 2013;54(9):2325–2340. https://doi.org/10.1194/jlr.R036012
  49. Sun Y, Zhang S, Nie Q, et al. Gut firmicutes: Relationship with dietary fiber and role in host homeostasis. Crit Rev Food Sci Nutr. 2023;63(33):12073–12088. https://doi.org/10.1080/10408398.2022.2098249
  50. Magne F, Gotteland M, Gauthier L, et al. The firmicutes/bacteroidetes ratio: A relevant marker of gut dysbiosis in obese patients? Nutrients. 2020;12(5): 1474. https://doi.org/10.3390/nu12051474
  51. Flint HJ, Scott KP, Duncan SH, Louis P, Forano E. Microbial degradation of complex carbohydrates in the gut. Gut Microbes. 2012;3(4):289–306. https://doi.org/10.4161/gmic.19897
  52. Bender JM, Li F, Martelly S, et al. Maternal HIV infection influences the microbiome of HIV-uninfected infants. Sci Transl Med. 2016;8(349):349ra100. https://doi.org/10.1126/scitranslmed.aaf5103
  53. Liu Y, Wang J, Wu C. Modulation of gut microbiota and immune system by probiotics, pre-biotics, and post-biotics. Front Nutr. 2022;8:634897. https://doi.org/10.3389/fnut.2021.634897
  54. Duranti S, Longhi G, Ventura M, Van Sinderen D. Exploring the ecology of bifidobacteria and their genetic adaptation to the mammalian gut. Microorganisms. 2020;9(1):8. https://doi.org/10.3390/microorganisms9010008
  55. Arrieta M-C, Stiemsma LT, Amenyogbe N, Brown EM, Finlay B. The intestinal microbiome in early life: Health and disease. Front Immunol. 2014;5:427. https://doi.org/10.3389/fimmu.2014.00427

Appendix 1

BOX 1: Supplementary document showing some of the search strategies.


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