scholarly journals Cotrimoxazole Prophylaxis Increases Resistance Gene Prevalence and α-Diversity but Decreases β-Diversity in the Gut Microbiome of Human Immunodeficiency Virus–Exposed, Uninfected Infants

2019 ◽  
Vol 71 (11) ◽  
pp. 2858-2868 ◽  
Author(s):  
Alaric W D’Souza ◽  
Eshia Moodley-Govender ◽  
Bertram Berla ◽  
Tejas Kelkar ◽  
Bin Wang ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antibiotic Resistance ◽  
Resistance Gene ◽  
Gut Microbiome ◽  
Cotrimoxazole Prophylaxis ◽  
Β Diversity ◽  
Α Diversity ◽  
Immunodeficiency Virus ◽  
Functional Pathway ◽  
Exposed Uninfected

Abstract 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.

scholarly journals A Randomized Controlled Trial of Isoniazid to Prevent Mycobacterium tuberculosis Infection in Kenyan Human Immunodeficiency Virus–Exposed Uninfected Infants

2020 ◽  
Author(s):  
Sylvia M LaCourse ◽  
Barbra A Richardson ◽  
John Kinuthia ◽  
A J Warr ◽  
Elizabeth Maleche-Obimbo ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Mycobacterium Tuberculosis ◽  
High Risk ◽  
Adverse Events ◽  
Controlled Trial ◽  
Preventive Therapy ◽  
Infection Prevalence ◽  
Mycobacterium Tuberculosis Infection ◽  
Immunodeficiency Virus ◽  
Exposed Uninfected

Abstract Background Human immunodeficiency virus (HIV)–exposed uninfected (HEU) infants in endemic settings are at high risk of tuberculosis (TB). For infants, progression from primary Mycobacterium tuberculosis (Mtb) infection to TB disease can be rapid. We assessed whether isoniazid (INH) prevents primary Mtb infection. Methods We conducted a randomized nonblinded controlled trial enrolling HEU infants 6 weeks of age without known TB exposure in Kenya. Participants were randomized (1:1) to 12 months of daily INH (10 mg/kg) vs no INH. Primary endpoint was Mtb infection at end of 12 months, assessed by interferon-γ release assay (QuantiFERON-TB Gold Plus) and/or tuberculin skin test (TST, added 6 months after first participant exit). Results Between 15 August 2016 and 6 June 2018, 416 infants were screened, with 300 (72%) randomized to INH or no INH (150 per arm); 2 were excluded due to HIV infection. Among 298 randomized HEU infants, 12-month retention was 96.3% (287/298), and 88.9% (265/298) had primary outcome data. Mtb infection prevalence at 12-month follow-up was 10.6% (28/265); 7.6% (10/132) in the INH arm and 13.5% (18/133) in the no INH arm (7.0 vs 13.4 per 100 person-years; hazard ratio, 0.53 [95% confidence interval {CI}, .24–1.14]; P = .11]), and driven primarily by TST positivity (8.6% [8/93] in INH and 18.1% [17/94] in no INH; relative risk, 0.48 [95% CI, .22–1.05]; P = .07). Frequency of severe adverse events was similar between arms (INH, 14.0% [21/150] vs no INH, 10.7% [16/150]; P = .38), with no INH-related adverse events. Conclusions Further studies evaluating TB preventive therapy to prevent or delay primary Mtb infection in HEU and other high-risk infants are warranted. Clinical Trials Registration NCT02613169.

Gut microbiome of the emerald ash borer, Agrilus planipennis Fairmaire, and its relationship with insect population density

2020 ◽  
Vol 96 (8) ◽  
Author(s):  
Judith Mogouong ◽  
Philippe Constant ◽  
Robert Lavallée ◽  
Claude Guertin
Keyword(s):  
Population Density ◽  
Gut Microbiome ◽  
Emerald Ash Borer ◽  
Agrilus Planipennis ◽  
Economic Damage ◽  
Taxonomic Structure ◽  
Rrna Gene ◽  
Local Conditions ◽  
Β Diversity ◽  
Α Diversity

ABSTRACT The gut microbial communities of beetles play crucial roles in their adaptive capacities. Environmental factors such as temperature or nutrition naturally affect the insect microbiome, but a shift in local conditions like the population density on a host tree could also lead to changes in the microbiota. The emerald ash borer (EAB), Agrilus planipennis Fairmaire, is an exotic wood borer that causes environmental and economic damage to ash trees in North America. This study aimed to describe the taxonomic structure of the EAB gut microbiome and explore its potential relationship with borer population size. The number of EAB adults collected per tree through a 75 km transect from an epicenter allowed the creation of distinct classes of population density. The Gammaproteobacteria and Ascomycota predominated in bacterial and fungal communities respectively, as determined by sequencing of the bacterial 16S rRNA gene and the fungal internal transcribed spacer ITS2. Species richness and diversity of the bacterial community showed significant dependence on population density. Moreover, α-diversity and β-diversity analysis revealed some indicator amplicon sequence variants suggesting that the plasticity of the gut microbiome could be related to the EAB population density in host trees.

scholarly journals Age-Related Changes in Expression of CXCR4 and CCR5 on Peripheral Blood Leukocytes from Uninfected Infants Born to Human Immunodeficiency Virus Type 1-Infected Mothers

2004 ◽  
Vol 11 (1) ◽  
pp. 229-234 ◽  
Author(s):  
Sharon Shalekoff ◽  
Glenda E. Gray ◽  
Caroline T. Tiemessen
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cord Blood ◽  
Peripheral Blood Leukocytes ◽  
Blood Leukocytes ◽  
Cross Sectional ◽  
Age Related ◽  
Immunodeficiency Virus ◽  
Sectional Analysis ◽  
Exposed Uninfected

ABSTRACT Cross-sectional analysis of human immunodeficiency virus-exposed, uninfected infants revealed high proportions of CXCR4-expressing cells in their cord blood, which declined at 4.5 months and increased between 9 and 15 months to levels approaching those of uninfected adults. Proportions of CCR5-expressing cells, however, were very low in cord blood and subsequently increased with age.

scholarly journals Gut microbiome as a response marker for pancreatic enzyme replacement therapy in a porcine model of exocrine pancreas insufficiency

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Sabrina Ritz ◽  
Daniela Hahn ◽  
Haleluya T. Wami ◽  
Karin Tegelkamp ◽  
Ulrich Dobrindt ◽  
...  
Keyword(s):  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Gut Microbiome ◽  
Pancreatic Enzyme ◽  
Microbial Composition ◽  
Enzyme Replacement ◽  
Β Diversity ◽  
Healthy State ◽  
Α Diversity ◽  
Pancreatic Enzyme Replacement Therapy

Abstract Background Exocrine pancreatic insufficiency (EPI) is characterized by the loss of active pancreatic enzymes and a resulting severely reduced food digestion. EPI therapy requires orally applied pancreatic enzyme replacement. The gut microbiome is a known mediator of intestinal diseases and may influence the outcome of EPI and the effects of a pancreatic enzyme replacement therapy (PERT). Here, we analyzed the effects of EPI and PERT on the gut microbiome in the model of pancreatic duct ligated minipigs. Results The microbial community composition in pig feces was analyzed by next generation sequencing of 16S rRNA amplicons. The data were evaluated for α- and β-diversity changes and changes at the different Operational Taxonomic Unit (OTU) levels by Shannon–Wiener and inverse Simpson index calculation as well as by Principal Coordinates Analysis based on Bray–Curtis dissimilarity. Microbial α-diversity was reduced after EPI induction and reverted to nearly healthy state after PERT. Analysis of microbial composition and β-diversity showed distinctive clusters of the three study groups and a change towards a composition comparable to healthy animals upon PERT. The relative abundance of possible pathobionts like Escherichia/Shigella, Acinetobacter or Stenotrophomonas was reduced by PERT. Conclusion These data demonstrate that EPI-induced dysbiosis could be reverted by PERT to a nearly healthy state. Elevated α-diversity and the reduction of bacterial overgrowth after PERT promises benefits for EPI patients. Non-invasive microbiome studies may be useful for EPI therapy monitoring and as marker for response to PERT.

scholarly journals The Effect of Probiotics Supplementation on the Gut Microbiome of Healthy Dogs Assessed Using Metagenomic Sequencing: A Randomized Control Trial

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1591-1591
Author(s):  
Jirayu Tanprasertsuk ◽  
Justin Shmalberg ◽  
Aashish Jha ◽  
LeeAnn Perry ◽  
Ryan Honaker
Keyword(s):  
Health Outcomes ◽  
Gut Microbiome ◽  
Randomized Control Trial ◽  
Gastrointestinal Diseases ◽  
Metagenomic Sequencing ◽  
Β Diversity ◽  
Α Diversity ◽  
Stool Samples ◽  
Healthy Dogs ◽  
Randomized Control

Abstract Objectives Dogs share similar gut microbiome (GM) with humans, making them a great model for investigating the effects of probiotics (PR) on GM and health. This randomized control trial examined changes in MB and health outcomes in household dogs after PR supplementation. Methods All dogs recruited were fed human grade cooked food ≥ 1 mo, not fed any cultured food, PR, prebiotics, or on antibiotics ≥ 3 mo, and absent of major diseases. Dogs were randomized to receive a daily dose of PR (20 billion CFU of L. reuteri, P. acidilactici, E. faecium, L. acidophilus, B. animalis, L. fermentum, L. rhamnosus) or placebo (PL) for 4 weeks. Owners completed a health survey and collected stool samples at baseline and 4 weeks after the intervention in both groups. Additional stool samples were collected 2 weeks after stopping the PR in the PR group. GM profiling was performed with metagenomic sequencing. Results Twenty three dogs in the PR and 19 dogs in the PL group completed the trial (5.6 ± 3.0 y, 69% male). PR had no effect on α-diversity. As compared to baseline, changes in β-diversity at the species level in 4.3% of GM were significantly affected by PR at week 4 (P < 0.001) but not at week 6. A significant increase (adj P < 0.01) for ≥ 2-fold in abundance was observed at week 4 as compared to baseline for 41 bacterial taxa, 29 (71%) of which belong in the Lactobacillus genus. The abundance of E. coli also decreased at week 4 in the PR group (2.8 folds, adj P < 0.01). The abundance of these taxa returned to baseline at week 6. Such changes in diversity or abundance were not observed with PL. Dogs fed PR tended to be at a lower risk of diarrhea during the trial (0% vs 16%, P = 0.08). No change in other health outcomes was observed. Conclusions Oral PR supplementation has a small but significant effect on GM in healthy dogs. Findings warrant further investigation with longer duration in populations at a higher risk of gastrointestinal diseases. Funding Sources NomNomNow Inc.

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