Infant gut microbiota characteristics generally do not modify effects of lipid-based nutrient supplementation on growth or inflammation: secondary analysis of a randomized controlled trial in Malawi

Abstract

An unhealthy gut microbial community may act as a barrier to improvement in growth and health outcomes in response to nutritional interventions. The objective of this analysis was to determine whether the infant microbiota modified the effects of a randomized controlled trial of lipid-based nutrient supplements (LNS) in Malawi on growth and inflammation at 12 and 18 months, respectively. We characterized baseline microbiota composition of fecal samples at 6 months of age (n = 506, prior to infant supplementation, which extended to 18 months) using 16S rRNA gene sequencing of the V4 region. Features of the gut microbiota previously identified as being involved in fatty acid or micronutrient metabolism or in outcomes relating to growth and inflammation, especially in children, were investigated. Prior to correction for multiple hypothesis testing, the effects of LNS on growth appeared to be modified by Clostridium (p-for-interaction = 0.02), Ruminococcus (p-for-interaction = 0.007), and Firmicutes (p-for-interaction = 0.04) and effects on inflammation appeared to be modified by Faecalibacterium (p-for-interaction = 0.03) and Streptococcus (p-for-interaction = 0.004). However, after correction for multiple hypothesis testing these findings were not statistically significant, suggesting that the gut microbiota did not alter the effect of LNS on infant growth and inflammation in this cohort.

Figure 1

Participant flow. Participant flow in CONSORT-recommended format. AGP: alpha 1-acid glycoprotein, CONSORT: Consolidated Standards of Reporting Trials, CRP: C-reactive protein, HCZ: head circumference z-score, LAZ: length-for-age z-score, WAZ: weight-for-age z-score, WLZ: weight-for-length z-score.

Figure 2

Heatmap of p-values for interaction. Heatmap displays levels of p-values for interactions with the LNS intervention. No p-values were less than 0.10 after correction for multiple hypothesis testing.

Figure 3

Growth outcomes exhibiting effect modification by 6 month gut microbiota characteristics, regarding the effect of LNS on change in z-scores from 6 to 12 months of age. Data shown are for effect modification interactions for which the p-value was < 0.05 before correction for multiple hypothesis testing.

Figure 4

Effect modification by 6 month gut microbiota characteristics, regarding the effect of LNS on inflammation at 18 months of age. Data shown are for effect modification interactions for which the p-value was < 0.05 before correction for multiple hypothesis testing.