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Cotrimoxazole Prophylaxis Increases Resistance Gene Prevalence and α-Diversity but Decreases β-Diversity in the Gut Microbiome of Human Immunodeficiency Virus–Exposed, Uninfected Infants
BACKGROUND: Prophylactic cotrimoxazole treatment is recommended in human immunodeficiency virus (HIV)–exposed, uninfected (HEU) infants, but the effects of this treatment on developing HEU infant gut microbiotas and resistomes are largely undefined. METHODS: We analyzed whole-metagenome sequencing d...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778358/ https://www.ncbi.nlm.nih.gov/pubmed/31832638 http://dx.doi.org/10.1093/cid/ciz1186 |
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author | D’Souza, Alaric W Moodley-Govender, Eshia Berla, Bertram Kelkar, Tejas Wang, Bin Sun, Xiaoqing Daniels, Brodie Coutsoudis, Anna Trehan, Indi Dantas, Gautam |
author_facet | D’Souza, Alaric W Moodley-Govender, Eshia Berla, Bertram Kelkar, Tejas Wang, Bin Sun, Xiaoqing Daniels, Brodie Coutsoudis, Anna Trehan, Indi Dantas, Gautam |
author_sort | D’Souza, Alaric W |
collection | PubMed |
description | BACKGROUND: Prophylactic cotrimoxazole treatment is recommended in human immunodeficiency virus (HIV)–exposed, uninfected (HEU) infants, but the effects of this treatment on developing HEU infant gut microbiotas and resistomes are largely undefined. METHODS: We analyzed whole-metagenome sequencing data from 163 longitudinally collected stool samples from 63 HEU infants randomized to receive (n = 34; CTX-T) or to not receive (n = 29; CTX-N) prophylactic cotrimoxazole treatment. We generated taxonomic, functional pathway, and resistance gene profiles for each sample and compared microbiome signatures between the CTX-T and CTX-N infants. RESULTS: Metagenomic analysis did not reveal significant differences in taxonomic or functional pathway α-diversity between CTX-T and CTX-N infants. In contrast, resistance gene prevalence (P = .00719) and α-diversity (P = .0045) increased in CTX-T infants. These differences increased over time for both resistance gene prevalence measured by log-normalized abundance (4-month mean, 0.71 [95% confidence interval {CI}, .2–1.2] and 6-month mean, 0.85 [95% CI, .1–1.7]) and α-diversity (P = .0045). Unlike α-diversity, interindividual gut microbiome taxonomic (mean, −0.11 [95% CI, −.15 to −.077]), functional taxonomic (mean, −0.050 [95% CI, −.084 to −.017]), and resistance gene (mean, −0.13 [95% CI, −.17 to −.099]) β-diversity decreased in CTX-T infants compared with CTX-N infants. These results are consistent with persistent antibiotic selection pressure. CONCLUSIONS: Cotrimoxazole prophylaxis in HEU infants decreased gut microbiome β-diversity and increased antibiotic resistance gene α-diversity and prevalence. Antibiotic resistance is a growing threat, especially in low- and middle-income countries where the higher perinatal HIV exposure rates result in cotrimoxazole prophylaxis. Understanding effects from current HEU infant antibiotic prophylaxis guidelines will inform guideline revisions and efforts to reduce increasing antibiotic resistance. |
format | Online Article Text |
id | pubmed-7778358 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-77783582021-01-07 Cotrimoxazole Prophylaxis Increases Resistance Gene Prevalence and α-Diversity but Decreases β-Diversity in the Gut Microbiome of Human Immunodeficiency Virus–Exposed, Uninfected Infants D’Souza, Alaric W Moodley-Govender, Eshia Berla, Bertram Kelkar, Tejas Wang, Bin Sun, Xiaoqing Daniels, Brodie Coutsoudis, Anna Trehan, Indi Dantas, Gautam Clin Infect Dis Major Articles and Commentaries BACKGROUND: Prophylactic cotrimoxazole treatment is recommended in human immunodeficiency virus (HIV)–exposed, uninfected (HEU) infants, but the effects of this treatment on developing HEU infant gut microbiotas and resistomes are largely undefined. METHODS: We analyzed whole-metagenome sequencing data from 163 longitudinally collected stool samples from 63 HEU infants randomized to receive (n = 34; CTX-T) or to not receive (n = 29; CTX-N) prophylactic cotrimoxazole treatment. We generated taxonomic, functional pathway, and resistance gene profiles for each sample and compared microbiome signatures between the CTX-T and CTX-N infants. RESULTS: Metagenomic analysis did not reveal significant differences in taxonomic or functional pathway α-diversity between CTX-T and CTX-N infants. In contrast, resistance gene prevalence (P = .00719) and α-diversity (P = .0045) increased in CTX-T infants. These differences increased over time for both resistance gene prevalence measured by log-normalized abundance (4-month mean, 0.71 [95% confidence interval {CI}, .2–1.2] and 6-month mean, 0.85 [95% CI, .1–1.7]) and α-diversity (P = .0045). Unlike α-diversity, interindividual gut microbiome taxonomic (mean, −0.11 [95% CI, −.15 to −.077]), functional taxonomic (mean, −0.050 [95% CI, −.084 to −.017]), and resistance gene (mean, −0.13 [95% CI, −.17 to −.099]) β-diversity decreased in CTX-T infants compared with CTX-N infants. These results are consistent with persistent antibiotic selection pressure. CONCLUSIONS: Cotrimoxazole prophylaxis in HEU infants decreased gut microbiome β-diversity and increased antibiotic resistance gene α-diversity and prevalence. Antibiotic resistance is a growing threat, especially in low- and middle-income countries where the higher perinatal HIV exposure rates result in cotrimoxazole prophylaxis. Understanding effects from current HEU infant antibiotic prophylaxis guidelines will inform guideline revisions and efforts to reduce increasing antibiotic resistance. Oxford University Press 2019-12-13 /pmc/articles/PMC7778358/ /pubmed/31832638 http://dx.doi.org/10.1093/cid/ciz1186 Text en © The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Major Articles and Commentaries D’Souza, Alaric W Moodley-Govender, Eshia Berla, Bertram Kelkar, Tejas Wang, Bin Sun, Xiaoqing Daniels, Brodie Coutsoudis, Anna Trehan, Indi Dantas, Gautam Cotrimoxazole Prophylaxis Increases Resistance Gene Prevalence and α-Diversity but Decreases β-Diversity in the Gut Microbiome of Human Immunodeficiency Virus–Exposed, Uninfected Infants |
title | Cotrimoxazole Prophylaxis Increases Resistance Gene Prevalence and α-Diversity but Decreases β-Diversity in the Gut Microbiome of Human Immunodeficiency Virus–Exposed, Uninfected Infants |
title_full | Cotrimoxazole Prophylaxis Increases Resistance Gene Prevalence and α-Diversity but Decreases β-Diversity in the Gut Microbiome of Human Immunodeficiency Virus–Exposed, Uninfected Infants |
title_fullStr | Cotrimoxazole Prophylaxis Increases Resistance Gene Prevalence and α-Diversity but Decreases β-Diversity in the Gut Microbiome of Human Immunodeficiency Virus–Exposed, Uninfected Infants |
title_full_unstemmed | Cotrimoxazole Prophylaxis Increases Resistance Gene Prevalence and α-Diversity but Decreases β-Diversity in the Gut Microbiome of Human Immunodeficiency Virus–Exposed, Uninfected Infants |
title_short | Cotrimoxazole Prophylaxis Increases Resistance Gene Prevalence and α-Diversity but Decreases β-Diversity in the Gut Microbiome of Human Immunodeficiency Virus–Exposed, Uninfected Infants |
title_sort | cotrimoxazole prophylaxis increases resistance gene prevalence and α-diversity but decreases β-diversity in the gut microbiome of human immunodeficiency virus–exposed, uninfected infants |
topic | Major Articles and Commentaries |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778358/ https://www.ncbi.nlm.nih.gov/pubmed/31832638 http://dx.doi.org/10.1093/cid/ciz1186 |
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