Intestinal microbiota composition and efficacy of iron supplementation in Peruvian children.

OBJECTIVE: Despite repeated public health interventions, anemia prevalence among children remains a concern. We use an evolutionary medicine perspective to examine the intestinal microbiome as a pathway underlying the efficacy of iron-sulfate treatment. This study explores whether gut microbiota composition differs between anemic children who respond and do not respond to treatment at baseline and posttreatment and if specific microbiota taxa remain associated with response to iron supplementation after controlling for relevant inflammatory and pathogenic variables. METHODS: Data come from 49 pre-school-aged anemic children living in San Juan de Lurigancho, Lima, Peru. We tested for differences in alpha and beta diversity using QIIME 2 and performed differential abundance testing in DESeq2 in R. We ran multivariate regression models to assess associations between abundance of specific taxa and response while controlling for relevant variables in Stata 17. RESULTS: While we found no evidence for gut microbiota diversity associated with child response to iron treatment, we observed several differential abundance patterns between responders and non-responders at both timepoints. Additionally, we present support for a nonzero relationship between lower relative abundance of Barnesiellaceae and response to iron supplementation in samples collected before and after treatment. CONCLUSION: While larger studies and more specific approaches are needed to understand the relationship between microbes and anemia in an epidemiological context, this study suggests that investigating nutritional status and pathogen exposure is key to better understanding the gut microbiome and impact of iron fortification.

Revisiting geophagy: An evolved sickness behavior to microbiome-mediated gastrointestinal inflammation.

Geophagy, the consumption of clay or similar substances, is known as an evolved behavior that protects vulnerable populations, such as pregnant women and children, against gastrointestinal injury. However, perplexing questions remain, like the presence of geophagy in the absence of overt gastrointestinal infection and the potential causal relationship between geophagy and iron deficiency anemia. In this review, we hypothesize that geophagy is an inflammation-mediated sickness behavior regulated via the vagus nerve. We further hypothesize that the gut microbiome plays a critical role in mediating the relationship between inflammation and geophagy. By including inflammation and the microbiome within the existing protection hypothesis, we can explain how subclinical gastrointestinal states induce geophagy. Furthermore, we can explain how gastrointestinal inflammation is responsible for both geophagy and iron-deficiency anemia, explaining why the two phenomena frequently co-occur. Ultimately, defining geophagy as a sickness behavior allows us to integrate the gut-brain axis into geophagy research.

Adiposity and pathogen exposure: An investigation of response to iron supplementation and hypothesized predictors in anemic pre-school-aged children living in a dual burden environment.

OBJECTIVES: Peruvians are experiencing rapid dietary and lifestyle changes, resulting in a phenomenon known as the "dual burden of disease." A common manifestation of the dual burden in individuals is the co-occurrence of overweight and anemia. Despite recent initiatives introduced to address these concerns, rates continue to be public health concerns. This study investigates the relationship between immune activation and lack of response to iron supplementation after 1 month of treatment and explores variation in body fat stores as a potential moderator between immune function and response to treatment. METHODS: Data come from children, aged 2-5 years (n = 50) from a peri-urban community in Lima, Peru. Multivariate logistic regression models were used to explore the associations between response to treatment (Hb > =11.0 g/dl) after 1 month of treatment), markers of immune activation (C-reactive protein [CRP] and reported morbidity symptoms), and measures of body fat (waist-to-height ratio, triceps skinfold thickness, and body mass index [BMI]). RESULTS: We found that high CRP is associated with a lack of response to iron supplementation after 1 month of treatment and that BMI z-score may moderate this association. Generally, larger body size is associated with response to iron supplementation whether or not the children in this sample have high immune activation. However, the probability of anemic children responding to iron supplementation treatment differed across adiposity measures. CONCLUSIONS: Our finding suggesting that adiposity and CRP influence response to iron supplementation, furthers our understanding of the relationship between inflammation and anemia treatment in children and has both theoretical and public health implications.

Child, caretaker, and community: Testing predictors of anemia and response to iron supplementation in Peruvian preschool-aged children.

OBJECTIVES: Despite repeated governmental and nongovernmental interventions, anemia remains a widespread public health concern in Peru. This article examines nutritional and disease factors associated with the prevalence of anemia and response to iron supplementation in Peruvian children, with the aim of understanding the lack of success of national programs. METHODS: Data come from children, aged 2-5 years (n = 102), living in peri-urban Lima. Predictors of anemia and response to iron supplementation were explored at the individual, maternal, household, and environmental levels using logistic regression models, adjusted for clustering by household. RESULTS: Half of the children in this sample were anemic and 50% of the anemic children responded to iron supplementation. We identified several factors that were associated with child anemia status and response to iron supplementation. Lower weight-for-age z-scores and the winter season were strong predictors of child anemia status and nonresponse to iron supplementation. Living with paternal grandparents was protective against anemia and elevated C-reactive protein at the time of the final interview was associated with a lack of response to iron supplementation. CONCLUSIONS: The findings of this study document an association between children's anemia status and their nutritional and ecological environment, highlighting the importance of examining anemia within a specific context to better understand the factors driving this important health problem.

Iron and infection: An investigation of the optimal iron hypothesis in Lima, Peru.

OBJECTIVES: This article explores the optimal iron hypothesis through secondary data analysis of the association between hemoglobin levels and morbidity among children living in Canto Grande, a peri-urban community located on the outskirts of Lima, Peru. METHODS: Risk ratios were used to test whether lower iron status, assessed using the HemoCue B-Hemoglobin System, was associated with an increased relative risk of morbidity symptoms compared to iron replete status, controlling for infant age, sex, weight for height z-score, maternal education, and repeated measures in 515 infants aged 6-12 months. RESULTS: Infants with fewer current respiratory and diarrheal morbidity symptoms had a lower risk of low iron deficiency compared to participants who were iron replete (P < .10). Infants with fewer current respiratory infection symptoms had a statistically significant (P < .05) reduction in risk of moderate iron deficiency compared to infants who were iron replete. CONCLUSION: In this study, morbidity status was not predictive of iron deficient status over a six-month interval period, but nonreplete iron status was shown to be associated with current morbidity symptoms. These results support investigating iron status as an allostatic system that responds to infection adaptively, rather than expecting an optimal preinfection value.