Potential Role of Microbiome in Tuberculosis

Completed

• Conditions: Tuberculosis

• Registration Number: NCT04985994
• Lead Sponsor: Khyber Medical University Peshawar

Brief Summary

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a deadly infectious disease and major global public health problem. Recent evidence from animal studies suggests that the microbiome plays a role in TB pathogenesis and immune response. However, until now, no similar study has been performed in humans and thus any influence of the microbiota on TB or vice versa remains unknown.

Detailed Description

Tuberculosis is among one of the most difficult to treat infections that require multidrug therapy for prolonged periods, in most cases 6-9 months. Treatment failure is still common and frequently observed (even where adherence to antibiotic therapy is maintained) in 15% of drug-susceptible infections and 31% for drug-resistant cases. Although poor patient compliance and the emergence of drug-resistant Mtb strains are generally implicated as a major cause of TB treatment failure, other factors such as the role of the microbiome in TB pathogenesis and reactivation are poorly considered.

The human microbiome is a consortium/collection of all microorganisms (bacteria, archaea, viruses, and fungi) colonizing different habitats in the human body such as skin, gut, and mucosal surfaces and living in a commensal relationship with each other. Emerging evidence suggests a crucial role of the microbiome in hosts physiology, nutritional status, and development of the functional immune system. Microbial dysbiosis is the change in microbial composition or functional potential that has been implicated both in infectious diseases status as well as the development of non-communicable disease in hosts ranging from immune mediated diseases to intergenerational obesity and even cancers. Microbial dysbiosis at different body sites has also been reported in TB-associated comorbidities such as diabetes mellitus and malnutrition. However, to date, the role of the microbiome and microbial dysbiosis is not clear in the context of TB infections in humans.

Therefore, this study aims to dissect the relationship between the microbiomes and its interaction with the immune system during TB infection, and anti-tuberculosis therapy in humans.

Study Timeline

• Study First Submitted: 2021-07-22
• Study First Submitted QC: 2021-07-22
• Study First Posted: 2021-08-02
• Study Start: 2021-08-22
• Primary Completion: 2024-03-31
• Study Completion: 2024-08-31
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-09
• Last Update Posted: 2024-10-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 450

Inclusion Criteria

1. Diagnosed with TB after detailed history collection, clinical examination and laboratory assessment (sputum culture positive).
2. Aged 18 - 65 years.
3. Willing to participate in the study.
4. Healthy controls are those who are free of TB symptoms, healthy on physical examination and with a negative sputum culture result.

Exclusion Criteria

1. Already on anti-TB treatment or previously treated for TB.
2. Severely anemic (Hb < 10g/dL).
3. Having diarrhea or other major gastrointestinal disorders.
4. Using or have used aminoglycoside or quinolones antibiotics in the past one month.
5. Using a medically prescribed diet or nutrition supplement.
6. Pregnant or lactating women.
7. Patients with liver or renal dysfunction, or having any other chronic disease condition.
8. Multidrug resistance TB patients

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Gut microbiome diversity and functional potential	2 Years	To explore the effect of TB infection and anti-tuberculosis therapy on gut microbiome diversity, functional potential and immune response in newly diagnosed TB patients from Pakistan.

Secondary Outcome Measures

Name	Time	Method
Baseline Gut microbiome	1 year	To determine gut microbiome diversity and functional potential at baseline and compare with healthy controls
Baseline Oral microbiome	1 year	To determine oral microbiome diversity and functional potential at baseline and compare with healthy controls
Gut microbiome and associated factors	1 year	3. To assess the relationship between gut microbiome and socio-demographic characteristics and dietary intake in TB patients at baseline, before the start of anti-tuberculosis treatment.
Microbial dysbiosis	Two years	To describe the occurrence of gut microbial dysbiosis and its association with adverse reaction and treatment failure in TB patients.
Microbial signatures	2 years	5. To identify specific oral and gut enterotypes associated with adverse reaction and unfavorable treatment outcomes.

Trial Locations

Locations (2)

Khyber Medical University; 🇵🇰 Peshawar, KP, Pakistan

DTO Peshawar; 🇵🇰 Peshawar, KP, Pakistan