Disorders of gut microbiota and fecal-serum metabolic patterns are associated with pulmonary tuberculosis and pulmonary tuberculosis comorbid type 2 diabetes mellitus

From BugSigDB
Needs review
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI Uniform resource identifier for web resources.
Authors
Wang Y, He X, Gao Y, Xue M, Zhang H, Sun L, He Q, Jin J
Journal
Microbiology spectrum
Year
2025
Keywords:
diabetes mellitus, fecal metabolites, gut microbiota, metabolic pathways, pulmonary tuberculosis
UNLABELLED: Pulmonary tuberculosis (PTB) and diabetes mellitus (DM) are prevalent chronic diseases with substantial implications for human health. DM patients are more susceptible to PTB, which exacerbates diabetes-related complications. However, the complex molecular mechanisms underlying the enhanced susceptibility of DM patients to PTB infection remain poorly understood. In this study, α- and β-diversity of gut microbiota was significantly reduced in PTB patients and PTB-DM patients. The abundances of families Lachnospiraceae and Ruminococcaceae in the the Firmicutes phylum were reduced in PTB patients and further diminished in PTB-DM patients. On the other hand, untargeted metabolomics in frozen serum and stool samples indicated that phenylalanine, tyrosine, and tryptophan biosynthesis, metabolites of arginine, proline, tryptophan, and histidine were consistently altered in PTB patients and PTB-DM patients, with significant upregulation of most metabolites. Amino acids like serine, proline, and histidine were both remarkably elevated in PTB and PTB-DM patients. The correlation network analysis reveals the relationships between the shared microbial biomarkers and the shared metabolic pathways. This research contributes to the exploration of pivotal diagnostic biomarkers for both patients with PTB and PTB accompanied by diabetes. Specifically, shared reductions were identified in the genera g-Roseburia, g-Ruminococcaceae_UCG.013, g-Ruminococcaceae_NK4A214, g-Lachnospiraceae_unclassified, and g-Firmicutes_unclassified in addition to notable regulation of amino acids, like glycine, serine, and histidine in patients with PTB and PTB-DM. Our study expands the comprehension of the intricate connections linking gut microbiota, fecal metabolites, and serum metabolites in PTB and PTB-DM patients. IMPORTANCE: This study expands the understanding of the complex links between gut microbiota, fecal metabolites, and serum metabolites in patients with PTB and PTB-DM through multi-omics techniques. It is helpful for us to understand the complex molecular mechanism of increased susceptibility to PTB infection in diabetic patients.

Experiment 1


Needs review

Curated date: 2025/07/22

Curator: Nuerteye

Revision editor(s): Nuerteye

Subjects

Location of subjects
China
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 , Diabetes mellitus lung TB,lung tuberculosis,pulmonary TB,pulmonary tuberculosis,Tuberculosis, Pulmonary,Pulmonary tuberculosis,Diabetes,diabetes,diabetes mellitus,diabetes mellitus (disease),Diabetes mellitus (disorder),Diabetes mellitus, NOS,Diabetes NOS,DM,DM - Diabetes mellitus,Diabetes mellitus
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Combination of healthy volunteers (Health) and pulmonary tuberculosis patients with diabetes mellitus (PTB-DM)
Group 1 name Corresponds to the case (exposed) group for case-control studies
pulmonary tuberculosis (PTB) patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Diagnosed via TB-PCR, AFB, Xpert, plus clinical TB
Group 0 sample size Number of subjects in the control (unexposed) group
26
Group 1 sample size Number of subjects in the case (exposed) group
13
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
Not received any anti-tuberculosis antibiotics or other treatments for tuberculosis prior to sample collection

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
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
2

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Chao1 Abundance-based estimator of species richness
decreased
Simpson Estimator of species richness and species evenness: more weight on species evenness
decreased

Signature 1

Needs review

Curated date: 2025/07/22

Curator: Nuerteye

Revision editor(s): Nuerteye

Source: Figure 3A and 3B

Description: Identification of differential microbial biomarkers. Cladogram visualized the most differentially abundant taxa identified by LEfSe among the three groups. Comparisons of microbiota bacteria among the three groups. The histogram showed the LDA score computed for genera differentially abundant between groups and identified using LEfSe. Health: healthy people, PTB: pulmonary tuberculosis, PTB-DM: pulmonary tuberculosis patients with diabetes mellitus.

Abundance in Group 1: increased abundance in pulmonary tuberculosis (PTB) patients

NCBI Quality ControlLinks
Faecalibacterium
unclassified Faecalibacterium
Blautia
Dorea
Anaerostipes
Bilophila
unclassified Blautia
Paraprevotella
unclassified Paraprevotella
uncultured Ruminococcus sp.
uncultured Faecalibacterium sp.

Revision editor(s): Nuerteye

Experiment 2


Needs review

Curated date: 2025/07/22

Curator: Nuerteye

Revision editor(s): Nuerteye

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Combination of pulmonary tuberculosis (PTB) and pulmonary tuberculosis patients with diabetes mellitus (PTB-DM) group
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Healthy participants in our study had normal lifestyles. In terms of diet, they maintained a balanced diet with a variety of foods. Their sleep patterns were regular, ensuring an adequate amount of sleep every night. They also engaged in regular physical exercise and had effective stress control methods.
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
none of the healthy participants had taken antibiotics within 1 year prior to sampling.

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Chao1 Abundance-based estimator of species richness
increased
Simpson Estimator of species richness and species evenness: more weight on species evenness
increased

Signature 1

Needs review

Curated date: 2025/07/22

Curator: Nuerteye

Revision editor(s): Nuerteye

Source: Figure 3A and 3B

Description: Identification of differential microbial biomarkers. Cladogram visualized the most differentially abundant taxa identified by LEfSe among the three groups. Comparisons of microbiota bacteria among the three groups. The histogram showed the LDA score computed for genera differentially abundant between groups and identified using LEfSe. Health: healthy people, PTB: pulmonary tuberculosis, PTB-DM: pulmonary tuberculosis patients with diabetes mellitus.

Abundance in Group 1: increased abundance in pulmonary tuberculosis (PTB) patients

NCBI Quality ControlLinks
Butyricicoccus
Clostridia
Clostridiaceae
Collinsella tanakaei
Eubacterium ventriosum
Eubacterium xylanophilum
Lachnospira
Rhodospirillales
Roseburia
Roseburia intestinalis
unclassified Lachnospiraceae
uncultured Roseburia sp.
ClostridialesClostridiales
RuminococcaceaeRuminococcaceae
Ruminococcaceae UCG 013Ruminococcaceae UCG 013
Erysipelatoclostridium SNUG30386Erysipelatoclostridium SNUG30386
Tyzzerella 3Tyzzerella 3
Bacteroides dnLKV9Bacteroides dnLKV9

Revision editor(s): Nuerteye

Experiment 3


Needs review

Curated date: 2025/07/22

Curator: Nuerteye

Revision editor(s): Nuerteye

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Combination of healthy volunteers (Health) and pulmonary tuberculosis (PTB) group
Group 1 name Corresponds to the case (exposed) group for case-control studies
pulmonary tuberculosis and diabetes mellitus (PTB–DM)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Individuals presenting typical diabetic symptoms (polyuria, polydipsia, unexplained weight loss), fasting blood glucose ≥11.1 mmol or random blood glucose levels ≥ 11.1 mmol/L, and age between 18 and 65 years
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
Not specified

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Chao1 Abundance-based estimator of species richness
decreased
Simpson Estimator of species richness and species evenness: more weight on species evenness
decreased

Signature 1

Needs review

Curated date: 2025/07/22

Curator: Nuerteye

Revision editor(s): Nuerteye

Source: Figure 3A and 3B

Description: Identification of differential microbial biomarkers. Cladogram visualized the most differentially abundant taxa identified by LEfSe among the three groups. Comparisons of microbiota bacteria among the three groups. The histogram showed the LDA score computed for genera differentially abundant between groups and identified using LEfSe. Health: healthy people, PTB: pulmonary tuberculosis, PTB-DM: pulmonary tuberculosis patients with diabetes mellitus.

Abundance in Group 1: increased abundance in pulmonary tuberculosis and diabetes mellitus (PTB–DM)

NCBI Quality ControlLinks
Lactobacillales
Bacilli
Fusobacteriales
Fusobacteriaceae
Fusobacterium
Fusobacterium mortiferum
Clostridium innocuumClostridium innocuum
Faecalibacterium

Revision editor(s): Nuerteye