Segatella copri and gut microbial ammonia metabolism contribute to chronic kidney disease pathogenesis – Nature

Report on the Role of Segatella copri and Gut Microbial Ammonia Metabolism in Chronic Kidney Disease Pathogenesis

Introduction

Chronic kidney disease (CKD) poses a significant global health burden, impacting millions worldwide and aligning with the United Nations Sustainable Development Goal (SDG) 3: Good Health and Well-being. Alterations in gut microbiota have been implicated in CKD; however, large-scale studies and mechanistic insights remain limited. This report summarizes findings from a comprehensive study analyzing gut metagenome data to elucidate the role of gut microbial ammonia metabolism in CKD pathogenesis, highlighting potential microbial-based therapeutic interventions.

Study Overview and Methodology

1. Population and Data Collection: The study analyzed gut metagenome data from 1,550 older individuals aged 65–93 years, with detailed kidney function measurements. This aligns with SDG 3 by focusing on aging populations and health monitoring.
2. Microbial Analysis: Identification of microbial species associated with kidney function was conducted, emphasizing the species Segatella copri.
3. Functional Pathway Investigation: The study examined microbial ammonia metabolism-related pathways and the asnA gene, encoding an ammonia-assimilating enzyme, to understand their association with kidney function.
4. Experimental Validation: Findings were replicated in two external studies and validated through in vivo and in vitro experiments involving mice and bacterial cultures.

Key Findings

Association Between Gut Microbiota and Kidney Function

• Segatella copri showed a positive association with kidney function, mediated through microbial ammonia metabolism pathways.
• The asnA gene was identified as crucial in ammonia assimilation, contributing to improved kidney function.
• These associations were consistently replicated across independent external studies, reinforcing the robustness of the findings.

Experimental Insights into Ammonia Metabolism and CKD Progression

• Ammonia supplementation in mice increased serum creatinine and blood urea nitrogen levels, accelerating CKD progression.
• In vitro cultures of S. copri and asnA-overexpressing Escherichia coli effectively reduced ammonia concentrations.
• Ammonia reduction was significantly impaired in asnA-knockout S. copri, highlighting the gene’s functional importance.
• Gavage administration of S. copri or asnA-overexpressing E. coli mitigated ammonia-induced CKD progression in mice, whereas asnA-knockout S. copri did not.

Implications for Sustainable Development Goals (SDGs)

SDG 3: Good Health and Well-being

This study contributes to SDG 3 by advancing understanding of CKD pathogenesis and identifying novel microbial targets for therapeutic intervention, potentially improving health outcomes and quality of life for affected populations.

SDG 9: Industry, Innovation, and Infrastructure

The research employs innovative metagenomic and microbiological techniques, fostering scientific advancement and infrastructure development in biomedical research.

SDG 10: Reduced Inequalities

By focusing on older adults, a vulnerable demographic often facing health disparities, the study supports efforts to reduce health inequalities through targeted interventions.

SDG 17: Partnerships for the Goals

The collaborative nature of this research, involving multiple institutions and international cohorts, exemplifies partnerships essential for achieving global health objectives.

Conclusions and Future Directions

The findings underscore the critical role of gut microbial ammonia metabolism, particularly mediated by Segatella copri and the asnA gene, in the pathogenesis of chronic kidney disease. These insights open avenues for microbial-based therapeutic strategies to mitigate CKD progression, aligning with global health priorities under the SDGs.

Recommendations

• Further research to develop and test microbial interventions targeting ammonia metabolism in CKD patients.
• Integration of gut microbiome analysis into clinical assessment of CKD to personalize treatment approaches.
• Promotion of interdisciplinary and international collaborations to accelerate translational research in this field.

1. Sustainable Development Goals (SDGs) Addressed or Connected

1. SDG 3: Good Health and Well-being
   • The article focuses on chronic kidney disease (CKD), a significant health issue affecting older adults, and explores gut microbiota’s role in CKD pathogenesis and potential therapeutic interventions.
   • This aligns with SDG 3’s aim to ensure healthy lives and promote well-being for all at all ages, including reducing mortality from non-communicable diseases.
2. SDG 9: Industry, Innovation and Infrastructure
   • The study employs advanced metagenomic data analysis and genetic engineering techniques (e.g., gene knockout and overexpression in bacteria), reflecting innovation in health research and biotechnology.
3. SDG 17: Partnerships for the Goals
   • The research involves multiple institutions and international collaborations, supported by national and municipal science programs, embodying partnerships to achieve health-related goals.

2. Specific Targets Under the Identified SDGs

1. SDG 3: Good Health and Well-being
   • Target 3.4: By 2030, reduce by one third premature mortality from non-communicable diseases through prevention and treatment and promote mental health and well-being.
   • Target 3.b: Support the research and development of vaccines and medicines for the communicable and non-communicable diseases that primarily affect developing countries.
2. SDG 9: Industry, Innovation and Infrastructure
   • Target 9.5: Enhance scientific research, upgrade the technological capabilities of industrial sectors, including health-related biotechnology.
3. 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.

3. Indicators Mentioned or Implied to Measure Progress Towards the Targets

1. Indicators related to CKD and health outcomes (SDG 3):
   • Estimated Glomerular Filtration Rate (eGFR) – used as a measure of kidney function in the study.
   • Serum creatinine and blood urea nitrogen (BUN) levels – biochemical markers for kidney function and CKD progression.
   • Incidence and progression rates of chronic kidney disease among older adults.
2. Indicators related to scientific research and innovation (SDG 9):
   • Number of studies and publications on gut microbiota and CKD.
   • Development and application of microbial-based therapeutic interventions.
   • Use of genetic engineering techniques such as gene knockout and overexpression in research.
3. Indicators related to partnerships and collaboration (SDG 17):
   • Number of collaborative research projects and funding programs supporting CKD and microbiome research.
   • Data sharing and open access to metagenomic datasets and analysis codes.

4. Table of SDGs, Targets, and Indicators

Source: nature.com