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Interplay between the gut microbiome and typhoid fever: insights from endemic countries and a controlled human infection model – BioMed Central

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Interplay between the gut microbiome and typhoid fever: insights from endemic countries and a controlled human infection model – BioMed Central
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Interplay between the gut microbiome and typhoid fever: insights from endemic countries and a controlled human infection model  BioMed Central

 

Report on Gut Microbiome Dynamics, Infectious Diseases, and Alignment with Sustainable Development Goals

This report synthesizes findings from a collection of scientific literature, focusing on the interplay between the gut microbiome, host immunity, and infectious diseases, particularly enteric fevers. The research presented holds significant implications for achieving several United Nations Sustainable Development Goals (SDGs), most notably SDG 3 (Good Health and Well-being) and SDG 6 (Clean Water and Sanitation).

The Gut Microbiome’s Role in Host Defense and Disease

The human gut microbiome is a critical component of health, influencing immunity, inflammation, and resistance to pathogens. Understanding these dynamics is fundamental to advancing global health objectives outlined in SDG 3.

Microbiome-Mediated Immunity and Colonization Resistance

A healthy gut microbiota provides colonization resistance against enteric pathogens like Salmonella. This protective function is a key area of research with direct relevance to preventing communicable diseases.

  • Commensal bacteria produce metabolites, such as butyrate, that promote regulatory T-cell generation and inhibit the expansion of pathogenic bacteria (Arpaia et al., 2013; Byndloss et al., 2017; Kullberg et al., 2024).
  • The microbiota plays a well-established role in overall immunity and inflammation, highlighting its importance as a target for therapeutic intervention (Belkaid & Hand, 2014; Shreiner et al., 2015).
  • Specific commensal-produced metabolites have been shown to directly mediate resistance to Salmonella infection, offering potential avenues for novel anti-infective strategies (Jacobson et al., 2018).

Dysbiosis and Association with Chronic and Infectious Diseases

Disruptions in the gut microbiome (dysbiosis) are linked to a variety of diseases, from inflammatory bowel disease (IBD) to colorectal cancer and increased susceptibility to infection. Addressing these links contributes to the SDG 3 target of reducing mortality from non-communicable diseases and ending epidemics.

  • Studies have identified specific microbial signatures associated with colorectal cancer in diverse populations, such as in Morocco and Kenya (Allali et al., 2018; Obuya et al., 2022).
  • Microorganisms linked to IBD-associated dysbiosis have been shown to differentially impact host physiology (Hoffmann et al., 2016).
  • The composition of the gut microbiome has been correlated with clinical outcomes following infection with Salmonella Typhi, suggesting that the pre-infection state of the microbiome can determine disease severity (Zhang et al., 2018).

Enteric Fever: A Global Health Challenge Linked to SDG 3 and SDG 6

Typhoid and paratyphoid fevers remain a significant global burden, particularly in low- and middle-income countries. Research into their transmission, pathogenesis, and prevention is crucial for achieving SDG 3.3 (end the epidemics of communicable diseases) and SDG 6 (ensure availability and sustainable management of water and sanitation for all).

Global Burden and Environmental Risk Factors

The transmission of enteric fever is closely tied to environmental conditions, especially access to safe water and sanitation.

  • Systematic analyses confirm the substantial global burden of typhoid and paratyphoid fevers, underscoring the need for integrated control strategies (Stanaway et al., 2019; Meiring et al., 2021).
  • Risk factors identified in endemic areas like Jakarta, Indonesia, and Blantyre, Malawi, include contaminated food and water sources, directly linking disease incidence to the goals of SDG 6 (Vollaard et al., 2004; Gauld et al., 2020).
  • Asymptomatic carriage and stool shedding of S. Typhi are critical for sustained transmission in endemic communities, complicating eradication efforts (Khanam et al., 2021; Qureshi et al., 2024).

Pathogenesis and Host-Pathogen Interactions

Understanding how Salmonella interacts with the host and its resident microbiota is key to developing effective vaccines and treatments.

  • Salmonella exploits host inflammation to outcompete the native microbiota, often by using inflammation-derived compounds as respiratory electron acceptors (Stecher et al., 2007; Winter et al., 2010).
  • Host immune responses, including the roles of interferon-γ and the IL-23 axis, are critical in controlling Salmonella infection (Bao et al., 2000; Godinez et al., 2011).
  • Recent studies show how Salmonella can re-engineer the intestinal environment to overcome colonization resistance even in the presence of an intact microbiota (Rogers et al., 2024).

Antimicrobial Resistance (AMR) and Global Surveillance

The rise of AMR is a critical threat to global health security and a major impediment to achieving SDG 3. Genomic surveillance and understanding AMR transmission are paramount.

Tracking AMR Through Global Partnerships and Technology

International collaboration and advanced bioinformatics are essential tools in the fight against AMR, directly supporting SDG 17 (Partnerships for the Goals).

  • Global resources like Pathogenwatch provide platforms for genomic prediction and surveillance of AMR in pathogens such as S. Typhi (Argimón et al., 2021).
  • The Comprehensive Antibiotic Resistance Database (CARD) is an expanding resource that supports machine learning and resistome prediction, enhancing global capacity to monitor AMR (Alcock et al., 2023).
  • Genomic epidemiological studies across countries like Bangladesh, Nepal, and Malawi have been instrumental in tracking the transmission of resistant Salmonella strains (Dyson et al., 2024).

Regional Trends in Antimicrobial Resistance

Surveillance studies from various regions highlight the local and global dimensions of the AMR crisis.

  • A decade-long study in Dhaka, Bangladesh, documented the bacterial etiology and rising antimicrobial resistance in bloodstream infections (Ahmed et al., 2017).
  • Long-term surveillance in Malawi (1998–2016) revealed significant trends in AMR in bloodstream infection isolates, providing critical data for local public health policy (Musicha et al., 2017).
  • Understanding antimicrobial use patterns, such as among subsistence farmers in Malawi, is crucial for designing effective public awareness campaigns to curb AMR (MacPherson et al., 2022).

Comprehensive Reference List

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SDGs, Targets, and Indicators Analysis

Which SDGs are addressed or connected to the issues highlighted in the article?

The provided list of references primarily focuses on research related to infectious diseases, gut health, and public health surveillance, which directly connects to several Sustainable Development Goals (SDGs). The main SDGs addressed are:

  • SDG 3: Good Health and Well-being

    This is the most prominent SDG, as the majority of the references investigate health-related issues. The articles cover the etiology of bloodstream infections (Ref 1), antimicrobial resistance (Ref 1, 3, 5, 44), the burden and control of specific infectious diseases like typhoid and paratyphoid fever (Ref 18, 20, 42, 43, 59, 61), the role of the gut microbiome in health and disease (Ref 8, 19, 56), and the development and efficacy of vaccines (Ref 48).

  • SDG 6: Clean Water and Sanitation

    This goal is addressed through its direct link to water-borne diseases. Enteric fevers like typhoid are often transmitted through contaminated water and food. Reference 22 explicitly investigates the “Domestic river water use and risk of typhoid fever,” directly linking water source quality to health outcomes. Other studies on typhoid in endemic areas (Ref 18, 63) implicitly highlight the challenges related to water and sanitation infrastructure.

  • SDG 17: Partnerships for the Goals

    The collaborative nature of the research cited is evident, pointing to the importance of partnerships. Many studies involve international collaborations across multiple institutions and countries (e.g., the STRATAA study in Bangladesh, Malawi, and Nepal, Ref 18, 20, 43). Furthermore, the development of global resources for surveillance and data sharing, such as the Comprehensive Antibiotic Resistance Database (CARD) (Ref 3) and Pathogenwatch (Ref 5), exemplifies global partnerships to tackle health challenges.

What specific targets under those SDGs can be identified based on the article’s content?

Based on the topics of the references, several specific SDG targets can be identified:

SDG 3: Good Health and Well-being

  • Target 3.3: By 2030, end the epidemics of AIDS, tuberculosis, malaria and neglected tropical diseases and combat hepatitis, water-borne diseases and other communicable diseases.

    The extensive research on typhoid and paratyphoid fevers (Ref 20, 42, 59), cholera (Ref 2), and Salmonella infections (Ref 7, 55, 60) directly contributes to understanding and combating these major water-borne and communicable diseases.

  • Target 3.b: Support the research and development of vaccines and medicines for the communicable and non-communicable diseases that primarily affect developing countries…

    The article list includes research on the “Safety and efficacy of a typhoid conjugate vaccine in Malawian Children” (Ref 48) and studies on human infection models (Ref 23, 64) used to test vaccines and treatments, directly aligning with this target.

  • Target 3.d: Strengthen the capacity of all countries, in particular developing countries, for early warning, risk reduction and management of national and global health risks.

    This target is supported by studies on antimicrobial resistance surveillance (Ref 1, 44), the development of global genomic surveillance platforms like Pathogenwatch (Ref 5), and research assessing the burden of enteric fever to inform public health policy (Ref 18, 43).

SDG 6: Clean Water and Sanitation

  • Target 6.1: By 2030, achieve universal and equitable access to safe and affordable drinking water for all.

    The study linking “domestic river water use and risk of typhoid fever” in Malawi (Ref 22) provides critical evidence of the health consequences of lacking access to safe water, reinforcing the importance of this target and providing data to monitor risks associated with unsafe sources.

SDG 17: Partnerships for the Goals

  • Target 17.6: Enhance North-South, South-South and triangular regional and international cooperation on and access to science, technology and innovation…

    The multi-country studies assessing the burden of enteric fever in Bangladesh, Malawi, and Nepal (Ref 18, 43) and the genomic epidemiology study across these nations (Ref 20) are clear examples of international scientific cooperation to address shared health problems.

Are there any indicators mentioned or implied in the article that can be used to measure progress towards the identified targets?

Yes, the references mention or imply several indicators that can be used to measure progress:

  • Incidence and Burden of Disease: Several studies focus on assessing the “burden of enteric fever” (Ref 18, 43) and the “global burden of typhoid and paratyphoid fevers” (Ref 59). The incidence rates and mortality data from such studies are direct indicators for tracking progress on Target 3.3.
  • Trends in Antimicrobial Resistance (AMR): Research on “antimicrobial resistance in bloodstream infections” in Dhaka (Ref 1) and Malawi (Ref 44) provides data on the prevalence of resistant pathogens. The proportion of infections that are resistant to standard antibiotics is a key indicator for Target 3.d, measuring a critical global health risk.
  • Vaccine Efficacy and Coverage: The study on the “safety and efficacy of a typhoid conjugate vaccine” (Ref 48) provides a direct indicator of the effectiveness of a public health intervention. Vaccine efficacy rates from clinical trials are crucial for implementing vaccination programs aimed at achieving Target 3.b.
  • Identification of Disease Risk Factors: Studies that identify and quantify risk factors, such as the link between “domestic river water use and risk of typhoid fever” (Ref 22) or risk factors in Jakarta (Ref 63), provide indicators of environmental and behavioral risks. These help measure progress towards Target 6.1 by highlighting populations that lack access to safe water.
  • Development of Global Health Resources: The creation and use of global databases like the “Comprehensive Antibiotic Resistance Database (CARD)” (Ref 3) and surveillance platforms like “Pathogenwatch” (Ref 5) serve as indicators of enhanced global cooperation and capacity for health risk management (Targets 17.6 and 3.d).

Summary Table of SDGs, Targets, and Indicators

SDGs Targets Indicators (with reference examples)
SDG 3: Good Health and Well-being 3.3: End epidemics of communicable diseases. Incidence and burden of enteric fevers (Ref: 43, 59).
SDG 3: Good Health and Well-being 3.d: Strengthen early warning and risk management. Trends in antimicrobial resistance in bloodstream infections (Ref: 1, 44).
SDG 3: Good Health and Well-being 3.b: Support R&D of vaccines and medicines. Efficacy rate of new vaccines (e.g., typhoid conjugate vaccine) (Ref: 48).
SDG 6: Clean Water and Sanitation 6.1: Achieve access to safe drinking water. Documented risk of disease from unsafe water sources (Ref: 22).
SDG 17: Partnerships for the Goals 17.6: Enhance international cooperation on science and technology. Execution of multi-country research programs and development of global data platforms (Ref: 18, 20, 5).

Source: microbiomejournal.biomedcentral.com

 

Interplay between the gut microbiome and typhoid fever: insights from endemic countries and a controlled human infection model – BioMed Central

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