Potential Role of Microbiome in Tuberculosis

Study Overview
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Brief Summary
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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
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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.

Official Title
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Exploring the Role of Microbiome in Susceptibility, Treatment Response and Outcome Among Tuberculosis Patients; a Prospective Cohort Study

Conditions
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Tuberculosis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with TB after detailed history collection, clinical examination and laboratory assessment (sputum culture positive). Aged 18 - 65 years. Willing to participate in the study. Healthy controls are those who are free of TB symptoms, healthy on physical examination and with a negative sputum culture result. Exclusion Criteria: Already on anti-TB treatment or previously treated for TB. Severely anemic (Hb < 10g/dL). Having diarrhea or other major gastrointestinal disorders. Using or have used aminoglycoside or quinolones antibiotics in the past one month. Using a medically prescribed diet or nutrition supplement. Pregnant or lactating women. Patients with liver or renal dysfunction, or having any other chronic disease condition. Multidrug resistance TB patients

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Tuberculosis Patients<br>Diagnosed with pulmonary TB after detailed history collection, clinical examination, and laboratory assessment (sputum culture positive). Aged 18 years or above. Willing to participate in the study. | |
| Healthy Volunteers<br>Healthy subjects with no symptoms or history of pulmonary TB Negative sputum culture Matched for sex and age (±5 years) with the TB patient group. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gut microbiome diversity and functional potential | 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. | 2 Years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline Gut microbiome | To determine gut microbiome diversity and functional potential at baseline and compare with healthy controls | 1 year | 
| Baseline Oral microbiome | To determine oral microbiome diversity and functional potential at baseline and compare with healthy controls | 1 year | 
| Gut microbiome and associated factors | 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. | 1 year | 
| Microbial dysbiosis | To describe the occurrence of gut microbial dysbiosis and its association with adverse reaction and treatment failure in TB patients. | Two years | 
| Microbial signatures | 5. To identify specific oral and gut enterotypes associated with adverse reaction and unfavorable treatment outcomes. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tuberculosis, Pulmonary TB, Microbiome, Immunity, Nutrition, Treatment response, Treatment Outcome, Gut microbiome, Oral Microbiome, Inflammation, Dietary intake