Effect of long-term azithromycin treatment on gut microbial diversity in children and adolescents with HIV-associated chronic lung diseaseResearch in context
Trym Thune Flygel,
Ahmed Bargheet,
Regina Esinam Abotsi,
Shantelle Claassen-Weitz,
Victoria Simms,
Erik Hjerde,
Kilaza Samson Mwaikono,
Grace Mchugh,
Dan Hameiri-Bowen,
Veronika Kuchařová Pettersen,
Rashida Abbas Ferrand,
Mark Nicol,
Jorunn Pauline Cavanagh,
Trond Flaegstad,
Evgeniya Sovershaeva
Affiliations
Trym Thune Flygel
Research Group of Child and Adolescent Health, Department of Clinical Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway; Department of Paediatrics, University Hospital of North Norway, Tromsø, Norway
Ahmed Bargheet
Research Group of Child and Adolescent Health, Department of Clinical Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway; Host-Microbe Interaction Research Group, Department of Medical Biology, UiT The Arctic University of Norway, Tromsø, Norway
Regina Esinam Abotsi
Department of Molecular and Cell Biology & Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa; Department of Pharmaceutical Microbiology, School of Pharmacy, University of Health and Allied Sciences, Volta, Ghana
Shantelle Claassen-Weitz
Division of Medical Microbiology, University of Cape Town, Cape Town, South Africa
Victoria Simms
MRC International Statistics and Epidemiology Group, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom
Erik Hjerde
Department of Chemistry, Norstruct, UiT The Arctic University of Norway, Tromsø, Norway
Kilaza Samson Mwaikono
Computational Biology Group and H3ABioNet, Department of Integrative Biomedical Sciences, University of Cape Town, Cape Town, South Africa; Department of Science and Laboratory Technology, Dar es Salaam Institute of Technology, Tanzania
Grace Mchugh
Biomedical Research and Training Institute, Harare, Zimbabwe
Dan Hameiri-Bowen
Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
Veronika Kuchařová Pettersen
Research Group of Child and Adolescent Health, Department of Clinical Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway; Host-Microbe Interaction Research Group, Department of Medical Biology, UiT The Arctic University of Norway, Tromsø, Norway
Rashida Abbas Ferrand
Biomedical Research and Training Institute, Harare, Zimbabwe; Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom
Mark Nicol
Department of Pharmaceutical Microbiology, School of Pharmacy, University of Health and Allied Sciences, Volta, Ghana; Marshall Centre, Division of Infection and Immunity, School of Biomedical Sciences, University of Western Australia, Perth, Australia
Jorunn Pauline Cavanagh
Research Group of Child and Adolescent Health, Department of Clinical Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway
Trond Flaegstad
Research Group of Child and Adolescent Health, Department of Clinical Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway; Department of Paediatrics, University Hospital of North Norway, Tromsø, Norway
Evgeniya Sovershaeva
Department of Paediatrics, University Hospital of North Norway, Tromsø, Norway; Department of Microbiology and Infection Control, Akershus University Hospital, Nordbyhagen, Norway; Corresponding author. Department of Microbiology and Infection Control, Akershus University Hospital, Nordbyhagen, Norway.
Summary: Background: HIV-associated chronic lung disease (HCLD) is common in children and adolescents growing up with HIV. The use of azithromycin (AZM) reduces the rate of acute respiratory exacerbations in this population, however, impact of this treatment on the gut microbiota and associations with blood-derived inflammatory markers have not been studied. Methods: Children and adolescents with HCLD in Harare, Zimbabwe and Blantyre, Malawi were recruited in a double-blind, placebo-controlled trial of once-weekly AZM or placebo for 48 weeks (BREATHE trial, NCT02426112). Rectal swabs were collected at inclusion (N = 346), 48 weeks (treatment end, N = 313), and 72 weeks (six months after treatment cessation, N = 244). The bacterial composition of fecal swabs was determined using 16S rRNA gene sequencing. Plasma biomarkers at inclusion and 48 weeks were measured using Luminex multiplex bead assay. Findings: At 48 weeks, bacterial α-diversity was significantly lower in the AZM group, with 27 bacterial genera showing differential abundance between the study groups. The placebo group exhibited higher interconnectivity between bacterial genera at 48 weeks compared to the AZM group. Correlations between the top seven differentially abundant genera and biomarkers observed at inclusion were no longer significant at 48 weeks in both groups. Depletion of Campylobacter persisted for six months after cessation of AZM treatment. Interpretation: Long-term AZM treatment in HCLD patients affects their gut bacterial composition at least 6 months after its cessation. The consequences of reduced bacterial diversity, such as altered interaction with the immune system and risk of resistance, need further investigation to understand how to optimise gut health during long-term antibiotic treatments. Funding: The study was funded by the Norwegian Research Council and Helse Nord (HNF 1387-17).
