Maternal HIV infection influences the microbiome of HIV-uninfected infants

Bender, Jeffrey M.; Li, Fan; Martelly, Shoria; Byrt, Erin; Rouzier, Vanessa; Leo, Marguerithe; Tobin, Nicole H.; Pannaraj, Pia S.; Adisetiyo, Helty; Rollie, Adrienne; Santiskulvong, Chintda; Wang, Shaung; Autran, Chloe; Bode, Lars; Fitzgerald, Daniel W.; Kuhn, Louise; Aldrovandi, Grace M.

doi:10.1126/scitranslmed.aaf5103

Cited by 99 publications

(153 citation statements)

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“…! In a subset of four studies (Canada 31 , Haiti 3 , USA (CA-FL) 5 , and USA (CA-MA-MO) 18 ) with available data on mode of delivery, the increase in microbial diversity associated with non-EBF was similar in the meta-analysis stratified on vaginally-delivered infants and on cesareandelivered infants (Supplementary figure 2).…”

Section: !mentioning

confidence: 96%

“…In sensitivity meta-analyses excluding estimates from either the USA (NC) study 29 (which contained a small number of infants ≤ 6 months old), or the Haiti study 3 (which included samples from HIV-uninfected infants born to HIV-infected and HIV-uninfected mothers) or the Vitamin D Antenatal Asthma Reduction Trial (VDAART) study 18 in the USA (CA-MA-MO) (which contained samples from infants at high risk of asthma and allergies, half of whom were randomized to high-dose antenatal vitamin D supplementation), the results remained similar (Supplementary figure 1).…”

Section: Gut Microbial Diversity Is Increased In Non-ebf Vs Ebf Infamentioning

confidence: 99%

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Effects of exclusive breastfeeding on infant gut microbiota: a meta-analysis across studies and populations

et al. 2018

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38Literature regarding the differences in gut microbiota between exclusively breastfed (EBF) and 39 non-EBF infants is meager with large variation in methods and results. We performed a meta-40 analysis of seven studies (a total of 1825 stool samples from 684 infants) to investigate effects of 41 EBF compared to non-EBF on infant gut microbiota across different populations. In the first 6 42 months of life, overall bacterial diversity, gut microbiota age, relative abundances of 43 Bacteroidetes and Firmicutes and microbial-predicted pathways related to carbohydrate 44 metabolism were consistently increased; while relative abundances of pathways related to lipid, 45 3 vitamin metabolism and detoxification were decreased in non-EBF vs. EBF infants. The 46 perturbation in microbial-predicted pathways associated with non-EBF was larger in infants 47 delivered by C-section than delivered vaginally. Longer duration of EBF mitigated diarrhea-48 associated gut microbiota dysbiosis and the effects of EBF persisted after 6 months of age. These 49 consistent findings across vastly different populations suggest that one of the mechanisms of 50 short and long-term benefits of EBF may be alteration in gut microbes. 51 52 Background 55Establishment of the gut microbiota in early life has substantial impact on subsequent health 1 . 56Common sources of the infant's intestinal microorganisms are from the mother's skin, vagina, 57 stool and from breastfeeding 2-5 . There is a close relationship between the infant's gut microbiota 58 and the mother's breast milk microbiota and human milk oligosaccharides (HMO) composition 59 6-9 . Indeed, recent evidence has shown that breast milk microbiota can directly seed the infant 60 gut microbiota and the effects of breastmilk on infant gut microbiota is dose-dependent 5 . The 61 microbiota in breast milk changes over time during lactation and has been shown to be different 62 between exclusive breastfeeding (EBF) vs. non-EBF mothers 10,11 . Gut microbial abundances in 63 breast-fed infants, especially bifidobacterial species, are correlated with the mother's HMOs and 64 HMO-related catabolic activity 3,12,13 . Infant gut microbiota have been shown to be different 65 between breast fed vs. formula-fed infants 14-20 and change rapidly during the transition from 66 breastfeeding to formula 21 . 67 68 4 EBF in the first 6 months of life provides a multitude of health benefits 22,23 . For example, EBF 69has been shown to be strongly protective against diarrhea morbidity and mortality 24 and 70 decreases long-term risk of diabetes and obesity as compared to non-EBF or formula-fed infants 71 [25][26][27] . We hypothesize that the numerous benefits of EBF may be in part due to its effects on the 72 infant gut microbiota. Several recent studies have identified varying differences in gut microbial 73 composition or diversity between EBF and non-EBF infants 5,28-30 or gradients in the gut 74 microbiota composition or diversity across EBF, non-EBF and non-breastfed (non-BF) infants 75 5,14,29,31,32 . H...

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Section: !mentioning

confidence: 96%

Section: Gut Microbial Diversity Is Increased In Non-ebf Vs Ebf Infamentioning

confidence: 99%

Effects of exclusive breastfeeding on infant gut microbiota: a meta-analysis across studies and populations

et al. 2018

Preprint

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“…Antibiotic use has been shown to be critical in the selection of virulent GBS strains (30). HIV-infected women are exposed more frequently to antibiotics for therapeutic or prophylactic use (31). Limited data exist regarding the GBS serotype distribution in HIV-infected mothers.…”

Section: Maternal Gbs Colonization In Hiv-infected Pregnant Womenmentioning

confidence: 99%

Increased Risk of Group B Streptococcus Invasive Infection in HIV-Exposed but Uninfected Infants: A Review of the Evidence and Possible Mechanisms

et al. 2016

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Group B Streptococcus (GBS) is a major cause of neonatal sepsis and mortality worldwide. Studies from both developed and developing countries have shown that HIV-exposed but uninfected (HEU) infants are at increased risk of infectious morbidity, as compared to HIV-unexposed uninfected infants (HUU). A higher susceptibility to GBS infections has been reported in HEU infants, particularly late-onset diseases and more severe manifestations of GBS diseases. We review here the possible explanations for increased susceptibility to GBS infection. Maternal GBS colonization during pregnancy is a major risk factor for early-onset GBS invasive disease, but colonization rates are not higher in HIV-infected compared to HIV-uninfected pregnant women, while selective colonization with more virulent strains in HIV-infected women is suggested in some studies. Lower serotype-specific GBS maternal antibody transfer and quantitative and qualitative defects of innate immune responses in HEU infants may play a role in the increased risk of GBS invasive disease. The impact of maternal antiretroviral treatment and its consequences on immune activation in HEU newborns are important to study. Maternal immunization presents a promising intervention to reduce GBS burden in the growing HEU population.

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“…Vertical transmission of microbes from various maternal body sites contribute to the developing infant gut microbiota, including the gut, vagina, skin and breast milk [1,2]. The bacterial contingent of this community, the microbiota, are known to affect our health in profound ways, bringing to the forefront the symbiotic relationship that exists between these microbes and their human host.…”

Section: Introductionmentioning

confidence: 99%

“…The bacterial contingent of this community, the microbiota, are known to affect our health in profound ways, bringing to the forefront the symbiotic relationship that exists between these microbes and their human host. Vertical transmission of microbes from various maternal body sites contribute to the developing infant gut microbiota, including the gut, vagina, skin and breast milk [1,2]. Many of these exert their influences during delivery or postpartum, after exposure to maternal vagina, stool and skin [3], but emerging evidence suggests that their influence may begin in utero.…”

Section: Introductionmentioning

confidence: 99%

Influence of maternal microbiota during pregnancy on infant immunity

Nyangahu

Jaspan

2019

Clinical and Experimental Immunology

102

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Microbiota from various maternal sites, including the gut, vagina and breast milk, are known to influence colonization in infants. However, emerging evidence suggests that these sites may exert their influence prior to delivery, in turn influencing fetal immune development. The dogma of a sterile womb continues to be challenged. Regardless, there is convincing evidence that the composition of the maternal gut prior to delivery influences neonatal immunity. Therefore, while the presence and function of placental microbiome is not clear, there is consensus that the gut microbiota during pregnancy is a critical determinant of offspring health. Data supporting the notion of bacterial translocation from the maternal gut to extra-intestinal sites during pregnancy are emerging, and potentially explain the presence of bacteria in breast milk. Much evidence suggests that the maternal gut microbiota during pregnancy potentially determines the development of atopy and autoimmune phenotypes in offspring. Here, we highlight the role of the maternal microbiota prior to delivery on infant immunity and predisposition to diseases. Moreover, we discuss potential mechanisms that underlie this phenomenon.

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Maternal HIV infection influences the microbiome of HIV-uninfected infants

Cited by 99 publications

References 47 publications

Effects of exclusive breastfeeding on infant gut microbiota: a meta-analysis across studies and populations

Effects of exclusive breastfeeding on infant gut microbiota: a meta-analysis across studies and populations

Increased Risk of Group B Streptococcus Invasive Infection in HIV-Exposed but Uninfected Infants: A Review of the Evidence and Possible Mechanisms

Influence of maternal microbiota during pregnancy on infant immunity

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