Excess fermentation and lactic acidosis as detrimental functions of the gut microbes in treatment-naive TB patients

Study information

Needs review

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

38440790

DOI Digital object identifier for electronic documents.

10.3389/fcimb.2024.1331521

URI Uniform resource identifier for web resources.

Authors

Yunusbaeva M, Borodina L, Terentyeva D, Bogdanova A, Zakirova A, Bulatov S, Altinbaev R, Bilalov F, Yunusbayev B

Journal

Frontiers in cellular and infection microbiology

Year

2024

Keywords:

anaerobic fermentation, dysbiosis, gut microbiome, gut-derived lactic acidosis, tuberculosis

INTRODUCTION: The link between gut microbiota and host immunity motivated numerous studies of the gut microbiome in tuberculosis (TB) patients. However, these studies did not explore the metabolic capacity of the gut community, which is a key axis of impact on the host's immunity. METHODS: We used deep sequencing of fecal samples from 23 treatment-naive TB patients and 48 healthy donors to reconstruct the gut microbiome's metabolic capacity and strain/species-level content. RESULTS: We show that the systematic depletion of the commensal flora of the large intestine, Bacteroidetes, and an increase in Actinobacteria, Firmicutes, and Proteobacteria such as Streptococcaceae, Erysipelotrichaceae, Lachnospiraceae, and Enterobacteriaceae explains the strong taxonomic divergence of the gut community in TB patients. The cumulative expansion of diverse disease-associated pathobionts in patients reached 1/4 of the total gut microbiota, suggesting a heavy toll on host immunity along with MTB infection. Reconstruction of metabolic pathways showed that the microbial community in patients shifted toward rapid growth using glycolysis and excess fermentation to produce acetate and lactate. Higher glucose availability in the intestine likely drives fermentation to lactate and growth, causing acidosis and endotoxemia. DISCUSSION: Excessive fermentation and lactic acidosis likely characterize TB patients' disturbed gut microbiomes. Since lactic acidosis strongly suppresses the normal gut flora, directly interferes with macrophage function, and is linked to mortality in TB patients, our findings highlight gut lactate acidosis as a novel research focus. If confirmed, gut acidosis may be a novel potential host-directed treatment target to augment traditional TB treatment.

Experiment 1

Edit History Delete

Mark reviewed

Your review change was submittedDuplicate this Experiment Add a new Signature

Needs review

Curated date: 2025/07/26

Curator: Nuerteye

Revision editor(s): Nuerteye

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: Pulmonary tuberculosis lung TB,lung tuberculosis,pulmonary TB,pulmonary tuberculosis,Tuberculosis, Pulmonary,Pulmonary tuberculosis

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

Group 1 name Corresponds to the case (exposed) group for case-control studies: Treatment‑naïve tuberculosis (TB) patients

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: pulmonary TB as confirmed by chest radiography and a positive sputum smear or were positive for M. tuberculosis based on the GeneXpert MTB/RIF test without evidence of rifampin resistance.

Group 0 sample size Number of subjects in the control (unexposed) group: 47

Group 1 sample size Number of subjects in the case (exposed) group: 23

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): use of anti-TB drugs within the past 30 days

Lab analysis

Sequencing type: WMS

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: Not specified

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: LEfSe

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

LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool: 4.5

Alpha Diversity

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

Signature 1

Edit History Delete

Mark reviewed

Your review change was submitted

Needs review

Curated date: 2025/07/26

Curator: Nuerteye

Revision editor(s): Nuerteye

Source: Figure 2B

Description: Taxonomic composition of the fecal microbiota of TB patients and healthy controls. Barplot depicting top bacterial species (LDA scores > 4.5) discriminating between groups.

Abundance in Group 1: increased abundance in Treatment‑naïve tuberculosis (TB) patients

NCBI	Quality Control	Links
Phocaeicola dorei
Escherichia coli
Akkermansia muciniphila
Prevotella copri clade CPrevotella copri clade C
Blautia wexlerae
Prevotella hominisPrevotella hominis
Megamonas funiformis

Revision editor(s): Nuerteye

Signature 2

Edit History Delete

Mark reviewed

Your review change was submitted

Needs review

Curated date: 2025/07/26

Curator: Nuerteye

Revision editor(s): Nuerteye

Source: Figure 2B

Description: Taxonomic composition of the fecal microbiota of TB patients and healthy controls. Barplot depicting top bacterial species (LDA scores > 4.5) discriminating between groups.

Abundance in Group 1: decreased abundance in Treatment‑naïve tuberculosis (TB) patients

NCBI	Quality Control	Links
Phocaeicola vulgatus
Alistipes putredinis
Prevotella copri clade BPrevotella copri clade B
Prevotella SGB1589Prevotella SGB1589
Prevotella SGB1680Prevotella SGB1680
Alistipes shahii
Parabacteroides merdae
Phocaeicola coprocola

Revision editor(s): Nuerteye