Sustained gut dysbiosis and intestinal inflammation show correlation with weight gain in person with chronic HIV infection on antiretroviral therapy

Study information

Reviewed Marked as Reviewed by Folakunmi on 2024-11-1

study design

time series / longitudinal observational

Citation

PMID PubMed identifier for scientific articles.

39044127

DOI Digital object identifier for electronic documents.

10.1186/s12866-024-03431-0

URI

Authors

Ishizaka A, Koga M, Mizutani T, Suzuki Y, Matano T, Yotsuyanagi H

Journal

BMC microbiology

Year

2024

Keywords:

Chronic inflammation, HIV, Microbiota

BACKGROUND: Person with human immunodeficiency virus type-1 (PWH) are prone to chronic inflammation due to residual viral production, even with antiretroviral therapy (ART), which increases the risk of age-related diseases. There is also limited information on changes in the intestinal environment of PWH during ART. In this longitudinal study, we investigated changes in the gut microbiota, persistence of chronic inflammation, interactions between the gut environment and inflammation, and metabolic changes in PWH using long-term ART. RESULTS: We analyzed changes in clinical parameters and gut microbiota in 46 PWH over a mean period of 4 years to understand the influence of gut dysbiosis on inflammation. Overall, changes in the gut microbiota included a decrease in some bacteria, mainly involved in short-chain fatty acid (SCFA) production, and an increase in certain opportunistic bacteria. Throughout the study period, an increase in bacterial-specific metabolic activity was observed in the intestinal environment. Continued decline in certain bacteria belonging to the Clostridia class and metabolic changes in gut bacteria involved in glucose metabolism. Additionally, patients with a low abundance of Parabacteroides exhibited low bacterial alpha diversity and a significant increase in body mass index (BMI) during the study period. Monocyte chemoattractant protein 1, a marker of macrophage activation in the plasma, continued to increase from baseline (first stool collection timepoint) to follow-up (second stool collection timepoint), demonstrating a mild correlation with BMI. Elevated BMI was mild to moderately correlated with elevated levels of plasma interleukin 16 and chemokine ligand 13, both of which may play a role in intestinal inflammation and bacterial translocation within the gut microbiota. The rate of BMI increase correlated with the rate of decrease in certain SCFA-producing bacteria, such as Anaerostipes and Coprococcus 3. CONCLUSION: Our data suggest that despite effective ART, PWH with chronic inflammation exhibit persistent dysbiosis associated with gut inflammation, resulting in a transition to an intestinal environment with metabolic consequences. Moreover, the loss of certain bacteria such as Parabacteroides in PWH correlates with weight gain and may contribute to the development of metabolic diseases.

Experiment 1

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Reviewed Marked as Reviewed by Folakunmi on 2024-11-1

Curated date: 2024/10/21

Curator: KateRasheed

Revision editor(s): KateRasheed

Subjects

Location of subjects: Japan

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: HIV-1 infection HIV-1 seropositive,Human Immunodeficiency Virus 1,Human Immunodeficiency Virus, Type 1,HIV-1 infection,hIV-1 infection

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Baseline

Group 1 name Corresponds to the case (exposed) group for case-control studies: Follow up

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Follow up refers to the study conducted four years after the initial gut microbiota analysis in 2018, where stool and blood samples were collected and analyzed for gut microbiota in 46 PWH(Person with human immunodeficiency virus type-1) receiving ART treatment. It is also referred to as second stool collection timepoint.

Group 0 sample size Number of subjects in the control (unexposed) group: 46

Group 1 sample size Number of subjects in the case (exposed) group: 46

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: MaAsLin2

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: Yes

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment: body mass index, age, sex, proton-pump inhibitor, Confounders controlled for: "antibiotic use" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.antibiotic use, Confounders controlled for: "statins" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.statins, alcohol drinking, smoking behavior

Alpha Diversity

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

Richness Number of species: unchanged

Signature 1

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Source: Fig. 1B

Description: Significant abundance of gut microbiota in PWH ( patients with human immunodeficiency virus (HIV) type-1); from baseline to follow-up period.

Abundance in Group 1: increased abundance in Follow up

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Cutibacterium
Staphylococcus
unclassified Burkholderiaceae
unclassified Corynebacterium
unclassified Enterobacteriaceae
Esherichia/ShigellaEsherichia/Shigella

Revision editor(s): KateRasheed

Signature 2

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Revision editor(s): KateRasheed

Source: Fig. 1B

Description: Significant abundance of gut microbiota in PWH ( patients with human immunodeficiency virus (HIV) type-1); from baseline to follow-up period.

Abundance in Group 1: decreased abundance in Follow up

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Blautia
Catenibacterium
Collinsella
Fusicatenibacter
Lysobacter
Ruminococcus gauvreauii

Revision editor(s): KateRasheed

Experiment 3

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Reviewed Marked as Reviewed by Folakunmi on 2024-11-1

Curated date: 2024/10/25

Curator: KateRasheed

Revision editor(s): KateRasheed

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Low BMI group

Group 1 name Corresponds to the case (exposed) group for case-control studies: High BMI group

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: High BMI group refers to patients having BMI over 25 at baseline.

Group 0 sample size Number of subjects in the control (unexposed) group: 30

Group 1 sample size Number of subjects in the case (exposed) group: 16

Lab analysis

Statistical Analysis

Statistical test: Mann-Whitney (Wilcoxon)

Signature 1

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Curated date: 2024/10/25

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Source: Fig. 3A

Description: Significant abundance of gut microbiota in BMI levels of PWH ( patients with human immunodeficiency virus (HIV) type-1); from baseline to follow-up period.

Abundance in Group 1: decreased abundance in High BMI group

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Parabacteroides
Alistipes

Revision editor(s): KateRasheed