Differences in the inflammatory proteome of East African and Western European adults and associations with environmental and dietary factors
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eLife assessment
Non-communicable diseases (NCDs) are rising rapidly in urbanizing populations in many parts of the developing world, including in sub-Saharan Africa. Temba and colleagues show important evidence that healthy Tanzanians display a pro-inflammatory phenotype with enrichment of specific immune-metabolic pathways. Dood-derived metabolites were identified as an important driver of inflammation-related molecules. These findings provide solid evidence that the dietary transition that occurs in urbanizing areas in sub-Saharan Africa may contribute significantly to the increased incidence of non communicable diseases in this part of the world.
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Abstract
Non-communicable diseases (NCDs) are rising rapidly in urbanizing populations in sub-Saharan Africa. Assessment of inflammatory and metabolic characteristics of a urbanizing African population and the comparison with populations outside Africa could provide insight in the pathophysiology of the rapidly increasing epidemic of NCDs, including the role of environmental and dietary changes. Using a proteomic plasma profiling approach comprising 92 inflammation-related molecules, we examined differences in the inflammatory proteome in healthy Tanzanian and healthy Dutch adults. We show that healthy Tanzanians display a pro-inflammatory phenotype compared to Dutch subjects, with enhanced activity of the Wnt/β-catenin signalling pathway and higher concentrations of different metabolic regulators such as 4E-BP1 and fibroblast growth factor 21. Among the Tanzanian volunteers, food-derived metabolites were identified as an important driver of variation in inflammation-related molecules, emphasizing the potential importance of lifestyle changes. These findings endorse the importance of the current dietary transition and the inclusion of underrepresented populations in systems immunology studies.
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Author Response
Reviewer #1 (Public Review):
This manuscript describes the differences in the plasma proteome and metabolome in healthy Tanzanian and healthy Dutch adults. The inflammatory plasma proteome was measured using the Olink 92 Inflammation panel, while the plasma metabolome was analyzed using a mass spectrometry-based untargeted approach. The plasma metabolome was measured only in the Tanzanian cohort. This study aimed to link the pro-inflammatory proteome of Tanzanian and Dutch healthy individuals with environmental factors and dietary lifestyles.
The correlation between the plasma proteome and food-derived metabolome profiles can shed light on the development of non-communicable diseases. This observation stresses the importance of dietary transition and lifestyle changes in expressing inflammation-related molecules. …
Author Response
Reviewer #1 (Public Review):
This manuscript describes the differences in the plasma proteome and metabolome in healthy Tanzanian and healthy Dutch adults. The inflammatory plasma proteome was measured using the Olink 92 Inflammation panel, while the plasma metabolome was analyzed using a mass spectrometry-based untargeted approach. The plasma metabolome was measured only in the Tanzanian cohort. This study aimed to link the pro-inflammatory proteome of Tanzanian and Dutch healthy individuals with environmental factors and dietary lifestyles.
The correlation between the plasma proteome and food-derived metabolome profiles can shed light on the development of non-communicable diseases. This observation stresses the importance of dietary transition and lifestyle changes in expressing inflammation-related molecules. Moreover, this study describes the inflammatory proteome profile in healthy Tanzanian individuals covering a cohort with limited studies. The molecular differences in circulating biomolecules between healthy individuals living in East Africa and individuals living in Western Europe and the correlations with intrinsic and environmental features are novel.
This study lacks a robust and solid validation of some of the differentially regulated circulating proteins and correlations between food-derived metabolites and proteins in a selected cohort. The discovery-driven approach in this manuscript highlights potential findings that need to be supported by a validation phase. According to this reviewer, the lack of such validation impacts the robustness of the results and the hypotheses generated. Due to that, the manuscript should incorporate validation experiments.
We acknowledge that our study was limited by the lack of a validation phase. To address this issue, we have undertaken additional analyses to validate our key findings related to the proteins associated with mTOR and Wnt/β-catenin pathways. These analyses involved data from a proof-of-concept intervention study conducted at the same site. Our response below provides more information on these validations.
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eLife assessment
Non-communicable diseases (NCDs) are rising rapidly in urbanizing populations in many parts of the developing world, including in sub-Saharan Africa. Temba and colleagues show important evidence that healthy Tanzanians display a pro-inflammatory phenotype with enrichment of specific immune-metabolic pathways. Dood-derived metabolites were identified as an important driver of inflammation-related molecules. These findings provide solid evidence that the dietary transition that occurs in urbanizing areas in sub-Saharan Africa may contribute significantly to the increased incidence of non communicable diseases in this part of the world.
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Reviewer #1 (Public Review):
This manuscript describes the differences in the plasma proteome and metabolome in healthy Tanzanian and healthy Dutch adults. The inflammatory plasma proteome was measured using the Olink 92 Inflammation panel, while the plasma metabolome was analyzed using a mass spectrometry-based untargeted approach. The plasma metabolome was measured only in the Tanzanian cohort. This study aimed to link the pro-inflammatory proteome of Tanzanian and Dutch healthy individuals with environmental factors and dietary lifestyles.
The correlation between the plasma proteome and food-derived metabolome profiles can shed light on the development of non-communicable diseases. This observation stresses the importance of dietary transition and lifestyle changes in expressing inflammation-related molecules. Moreover, this study …
Reviewer #1 (Public Review):
This manuscript describes the differences in the plasma proteome and metabolome in healthy Tanzanian and healthy Dutch adults. The inflammatory plasma proteome was measured using the Olink 92 Inflammation panel, while the plasma metabolome was analyzed using a mass spectrometry-based untargeted approach. The plasma metabolome was measured only in the Tanzanian cohort. This study aimed to link the pro-inflammatory proteome of Tanzanian and Dutch healthy individuals with environmental factors and dietary lifestyles.
The correlation between the plasma proteome and food-derived metabolome profiles can shed light on the development of non-communicable diseases. This observation stresses the importance of dietary transition and lifestyle changes in expressing inflammation-related molecules. Moreover, this study describes the inflammatory proteome profile in healthy Tanzanian individuals covering a cohort with limited studies. The molecular differences in circulating biomolecules between healthy individuals living in East Africa and individuals living in Western Europe and the correlations with intrinsic and environmental features are novel.
This study lacks a robust and solid validation of some of the differentially regulated circulating proteins and correlations between food-derived metabolites and proteins in a selected cohort. The discovery-driven approach in this manuscript highlights potential findings that need to be supported by a validation phase. According to this reviewer, the lack of such validation impacts the robustness of the results and the hypotheses generated. Due to that, the manuscript should incorporate validation experiments.
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Reviewer #2 (Public Review):
This study assessed the inflammatory and metabolic profiles of a healthy sub-Saharan Africa (Tanzania) population versus a healthy population outside Africa (Dutch). Using plasma samples from these cohorts, an O-Link proteomics inflammatory panel and targeted metabolomics platforms were utilised. The study shows that 'healthy' Tanzanians display an enhanced pro-inflammatory phenotype versus Dutch volunteers. Specific pathways and metabolites identified included - increase activation of the Wnt/Beta catenin pathway, and the metabolites 4E-BP1 and FGF21. The study highlights some interesting findings regarding the impact of diet on inflammatory pathway activation.
Major Strengths & Weaknesses - This is an interesting study and approach that aims to address some challenging questions in underrepresented …
Reviewer #2 (Public Review):
This study assessed the inflammatory and metabolic profiles of a healthy sub-Saharan Africa (Tanzania) population versus a healthy population outside Africa (Dutch). Using plasma samples from these cohorts, an O-Link proteomics inflammatory panel and targeted metabolomics platforms were utilised. The study shows that 'healthy' Tanzanians display an enhanced pro-inflammatory phenotype versus Dutch volunteers. Specific pathways and metabolites identified included - increase activation of the Wnt/Beta catenin pathway, and the metabolites 4E-BP1 and FGF21. The study highlights some interesting findings regarding the impact of diet on inflammatory pathway activation.
Major Strengths & Weaknesses - This is an interesting study and approach that aims to address some challenging questions in underrepresented populations. The findings demonstrate the importance of diet and dietary interventions on metabolic health, as well as key inflammatory proteins. It does raise the question whether anti-inflammatory therapies need to be targeted to specific at-risk populations, more so than other populations.
Impact - The study demonstrates the importance of considering differences between populations and the inclusion of underrepresented populations in such studies. The data suggests that lifestyle changes in sub-Saharan Africa are potentially contributing to altered inflammatory and metabolic profiles. Thus, health initiatives advocating traditional diets may alleviate the NCD epidemic in sub-Saharan Africa.
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