Intestinal microbiome analysis demonstrates azithromycin post-treatment effects improve when combined with lactulose

From BugSigDB
Reviewed Marked as Reviewed by Atrayees on 2023-7-10
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Nikolaou E, Kamilari E, Savkov D, Sergeev A, Zakharova I, Vogazianos P, Tomazou M, Antoniades A, Shammas C
Journal
World journal of pediatrics : WJP
Year
2020
Keywords:
Antibiotics, Azithromycin, Lactulose, Microbiome, Prebiotics
BACKGROUND: Next-generation sequencing has revolutionized our perspective on the gut microbiome composition, revealing the true extent of the adverse effects of antibiotics. The impact of antibiotic treatment on gut microbiota must be considered and researched to provide grounds for establishing new treatment strategies that are less devastating on commensal bacteria. This study investigates the impact on gut microbiome when a commonly used antibiotic, azithromycin is administered, as well as uncovers the benefits induced when it is used in combination with lactulose, a prebiotic known to enhance the proliferation of commensal microbes. METHODS: 16S rRNA gene sequencing analysis of stool samples obtained from 87 children treated with azithromycin in combination with or without lactulose have been determined. Children's gut microbial profile was established at the pre- and post-treatment stage. RESULTS: Azithromycin caused an increase in the relative abundance of opportunistic pathogens such as Streptococcus that was evident 60 days after treatment. While few days after treatment, children who also received lactulose started to show a higher relative abundance of saccharolytic bacteria such as Lactobacillus, Enterococcus, Anaerostipes, Blautia and Roseburia, providing a protective role against opportunistic pathogens. In addition, azithromycin-prebiotic combination was able to provide a phylogenetic profile more similar to the pre-treatment stage. CONCLUSION: It is suggested that during azithromycin treatment, lactulose is able to reinstate the microbiome equilibrium much faster as it promotes saccharolytic microbes and provides a homeostatic effect that minimizes the opportunistic pathogen colonization.

Experiment 1


Reviewed Marked as Reviewed by Folakunmi on 2024-2-21

Curated date: 2021/12/02

Curator: Mmarin

Revision editor(s): WikiWorks, LGeistlinger, Mmarin, Peace Sandy, Folakunmi

Subjects

Location of subjects
Russian Federation
Host species Species from which microbiome was sampled. Contact us to have more species added.
Homo sapiens
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Antimicrobial agent antibiotic,antibiotics,Antibiotika,Antibiotikum,antibiotique,antimicrobial,antimicrobial agents,microbicide,microbicides,Antimicrobial agent,antimicrobial agent
Group 0 name Corresponds to the control (unexposed) group for case-control studies
azithromycin-lactulose treated (day 0)
Group 1 name Corresponds to the case (exposed) group for case-control studies
azithromycin-lactulose treated (day 18)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
administered a single daily dosage of 10 mg/kg body weight azithromycin in addition with 20 mg/kg body weight lactulose per day, as powder for oral suspension.
Group 0 sample size Number of subjects in the control (unexposed) group
42
Group 1 sample size Number of subjects in the case (exposed) group
42

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V3-V4
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances
Statistical test
Mann-Whitney (Wilcoxon)
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05


Signature 1

Reviewed Marked as Reviewed by Folakunmi on 2024-2-20

Curated date: 2021/12/02

Curator: Mmarin

Revision editor(s): Mmarin

Source: Table 1

Description: AZ azithromycin. A and L represent higher mean relative abundance for the azithromycin only and azitrhomycin + lactulose groups, respectively Arrows point up or down indicate an increase or increase compared to the relative abundance at day 0, respectively

Abundance in Group 1: decreased abundance in azithromycin-lactulose treated (day 18)

NCBI Quality ControlLinks
Enterobacter
Prevotella

Revision editor(s): Mmarin

Signature 2

Reviewed Marked as Reviewed by Folakunmi on 2024-2-20

Curated date: 2021/12/02

Curator: Mmarin

Revision editor(s): Mmarin

Source: Table 1

Description: AZ azithromycin. A and L represent higher mean relative abundance for the azithromycin only and azitrhomycin + lactulose groups, respectively Arrows point up or down indicate an increase or increase compared to the relative abundance at day 0, respectively

Abundance in Group 1: increased abundance in azithromycin-lactulose treated (day 18)

NCBI Quality ControlLinks
Anaerostipes
Enterococcus
Lactobacillus
Roseburia
Ruminococcus

Revision editor(s): Mmarin

Experiment 2


Reviewed Marked as Reviewed by Folakunmi on 2024-2-21

Curated date: 2021/12/03

Curator: Mmarin

Revision editor(s): LGeistlinger, Mmarin, WikiWorks, Folakunmi

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
azithromycin treated (day 0)
Group 1 name Corresponds to the case (exposed) group for case-control studies
azithromycin treated (day 18)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
administered 10 mg/kg body weight per day of azithromycin, as powder for oral suspension.

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by Folakunmi on 2024-2-20

Curated date: 2021/12/03

Curator: Mmarin

Revision editor(s): Mmarin

Source: Table 1

Description: Arrows point up or down indicate an increase or increase compared to the relative abundance at day 0, respectively

Abundance in Group 1: decreased abundance in azithromycin treated (day 18)

NCBI Quality ControlLinks
Enterobacter

Revision editor(s): Mmarin

Signature 2

Reviewed Marked as Reviewed by Folakunmi on 2024-2-20

Curated date: 2021/12/03

Curator: Mmarin

Revision editor(s): Mmarin

Source: Table 1

Description: Arrows point up or down indicate an increase or increase compared to the relative abundance at day 0, respectively

Abundance in Group 1: increased abundance in azithromycin treated (day 18)

NCBI Quality ControlLinks
Adlercreutzia
Lachnospira

Revision editor(s): Mmarin

Experiment 3


Reviewed Marked as Reviewed by Folakunmi on 2024-2-21

Curated date: 2021/12/03

Curator: Mmarin

Revision editor(s): LGeistlinger, Mmarin, WikiWorks, Folakunmi

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
azithromycin treated (day 60)

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by Folakunmi on 2024-2-20

Curated date: 2021/12/03

Curator: Mmarin

Revision editor(s): Mmarin

Source: Table 1

Description: Arrows point up or down indicate an increase or increase compared to the relative abundance at day 0, respectively

Abundance in Group 1: decreased abundance in azithromycin treated (day 60)

NCBI Quality ControlLinks
Enterobacter
Odoribacter
Paraprevotella
Prevotella
Sutterella

Revision editor(s): Mmarin

Signature 2

Reviewed Marked as Reviewed by Folakunmi on 2024-2-20

Curated date: 2021/12/03

Curator: Mmarin

Revision editor(s): Mmarin

Source: Table 1

Description: Arrows point up or down indicate an increase or increase compared to the relative abundance at day 0, respectively

Abundance in Group 1: increased abundance in azithromycin treated (day 60)

NCBI Quality ControlLinks
Adlercreutzia
Alkaliphilus
Streptococcus
Veillonella

Revision editor(s): Mmarin

Experiment 4


Reviewed Marked as Reviewed by Folakunmi on 2024-2-21

Curated date: 2021/12/03

Curator: Mmarin

Revision editor(s): LGeistlinger, Mmarin, WikiWorks, Folakunmi

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
azithromycin treated (0-18)
Group 1 name Corresponds to the case (exposed) group for case-control studies
azithromycin-lactulose treated (0-18)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
administered a single daily dosage of 10 mg/kg body weight azithromycin in addition with 20 mg/kg body weight lactulose per day, as powder for oral suspension.

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Richness Number of species
unchanged

Signature 1

Reviewed Marked as Reviewed by Folakunmi on 2024-2-20

Curated date: 2021/12/03

Curator: Mmarin

Revision editor(s): Mmarin, Folakunmi

Source: Table 1

Description: AZ azithromycin. A and L represent higher mean relative abundance for the azithromycin only and azitrhomycin + lactulose groups, respectively Arrows point up or down indicate an increase or increase compared to the relative abundance at day 0, respectively

(day 18)

Abundance in Group 1: increased abundance in azithromycin-lactulose treated (0-18)

NCBI Quality ControlLinks
Anaerostipes

Revision editor(s): Mmarin, Folakunmi

Signature 2

Reviewed Marked as Reviewed by Folakunmi on 2024-2-20

Curated date: 2021/12/03

Curator: Mmarin

Revision editor(s): Mmarin, Folakunmi

Source: Table 1

Description: AZ azithromycin. A and L represent higher mean relative abundance for the azithromycin only and azitrhomycin + lactulose groups, respectively Arrows point up or down indicate an increase or increase compared to the relative abundance at day 0, respectively

(day 60)

Abundance in Group 1: increased abundance in azithromycin-lactulose treated (0-18)

NCBI Quality ControlLinks
Streptococcus

Revision editor(s): Mmarin, Folakunmi

Experiment 5


Reviewed Marked as Reviewed by Folakunmi on 2024-2-21

Curated date: 2024/02/20

Curator: Folakunmi

Revision editor(s): Folakunmi

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
azithromycin treated (0-60)
Group 1 name Corresponds to the case (exposed) group for case-control studies
azithromycin-lactulose treated (0-60)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
patients administered a single daily dosage of 10 mg/kg body weight azithromycin in addition with 20 mg/kg body weight lactulose per day, as powder for oral suspension.

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Richness Number of species
unchanged

Signature 1

Reviewed Marked as Reviewed by Folakunmi on 2024-2-20

Curated date: 2024/02/20

Curator: Folakunmi

Revision editor(s): Folakunmi

Source: Table 1

Description: Significant differences in relative abundance between groups and time points

Abundance in Group 1: increased abundance in azithromycin-lactulose treated (0-60)

NCBI Quality ControlLinks
Dysgonomonas

Revision editor(s): Folakunmi

Signature 2

Reviewed Marked as Reviewed by Folakunmi on 2024-2-20

Curated date: 2024/02/20

Curator: Folakunmi

Revision editor(s): Folakunmi

Source: Table 1

Description: Significant differences in relative abundance between groups and time points

Abundance in Group 1: decreased abundance in azithromycin-lactulose treated (0-60)

NCBI Quality ControlLinks
Alkaliphilus
Streptococcus

Revision editor(s): Folakunmi

Experiment 6


Reviewed Marked as Reviewed by Folakunmi on 2024-2-21

Curated date: 2024/02/20

Curator: Folakunmi

Revision editor(s): Folakunmi

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
azithromycin treated at day 18
Group 1 name Corresponds to the case (exposed) group for case-control studies
azithromycin-lactulose at day 18

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Richness Number of species
unchanged

Signature 1

Reviewed Marked as Reviewed by Folakunmi on 2024-2-20

Curated date: 2024/02/20

Curator: Folakunmi

Revision editor(s): Folakunmi

Source: Table 1

Description: Significant differences in relative abundance between groups at day 18 time point

Abundance in Group 1: increased abundance in azithromycin-lactulose at day 18

NCBI Quality ControlLinks
Anaerostipes
Blautia
Butyricimonas
Coprobacillus
Erysipelothrix
Megasphaera

Revision editor(s): Folakunmi

Experiment 7


Reviewed Marked as Reviewed by Folakunmi on 2024-2-21

Curated date: 2024/02/20

Curator: Folakunmi

Revision editor(s): Folakunmi

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
azithromycin treated at day 60
Group 1 name Corresponds to the case (exposed) group for case-control studies
azithromycin-lactulose at day 60

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Richness Number of species
unchanged

Signature 1

Reviewed Marked as Reviewed by Folakunmi on 2024-2-20

Curated date: 2024/02/20

Curator: Folakunmi

Revision editor(s): Folakunmi

Source: Table 1

Description: Significant differences in relative abundance between groups at day 20 time point

Abundance in Group 1: increased abundance in azithromycin-lactulose at day 60

NCBI Quality ControlLinks
Dysgonomonas

Revision editor(s): Folakunmi

Signature 2

Reviewed Marked as Reviewed by Folakunmi on 2024-2-20

Curated date: 2024/02/20

Curator: Folakunmi

Revision editor(s): Folakunmi

Source: Table 1

Description: Significant differences in relative abundance between groups at day 20 time point

Abundance in Group 1: decreased abundance in azithromycin-lactulose at day 60

NCBI Quality ControlLinks
Alkaliphilus
Streptococcus

Revision editor(s): Folakunmi

Experiment 8


Reviewed Marked as Reviewed by Folakunmi on 2024-2-21

Curated date: 2024/02/20

Curator: Folakunmi

Revision editor(s): Folakunmi

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
azithromycin-lactulose treated (day 0)
Group 1 name Corresponds to the case (exposed) group for case-control studies
azithromycin-lactulose treated (day 60)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
administered a single daily dosage of 10 mg/kg body weight azithromycin in addition with 20 mg/kg body weight lactulose per day, as powder for oral suspension.

Lab analysis

Statistical Analysis