Host-microbiota interactions in the infant gut revealed by daily faecal sample time series

Abstract

Aim: This study aims to explore the interplay between host immune factors and gut microbiota in human infants in vivo using time-series daily stool samples and identify biomarkers of host-microbe interactions. Methods: 216 faecal samples collected from infants aged 5-6 or 11-12 months were analysed for gut microbiota composition, total bacterial load, and biomarkers of immune function. Results: We identified indications of microbial stimulation of eosinophil cationic protein (ECP), IgA, calprotectin (Cal), intestinal alkaline phosphatase (IAP), and Bactericidal/permeability-increasing protein (BPI) at 6 and 12 months, as well as stimulation of lipocalin 2 (LCN2), lactoferrin (LTF), and alpha-defensin-5 only at 6 months. The associations between biomarker concentrations and bacterial population growth were primarily positive at 6 months and mostly negative at 12 months, suggesting increasing host regulation of the microbiota with age. The exceptions were IAP, which was predictive of declining bacterial populations at both time points, and Cal, whose associations changed from negative at 6 months to positive at 12 months. Conclusion: There is an age-associated development in the correlation pattern between bacterial population growth and the biomarker concentrations, suggesting that host-microbe interactions change during early development. Albumin appeared as a potential marker of gut permeability, while LCN2 seemed to correlate with gut transit time. Mucin degradation appeared to decrease with age. Mucin2 and IAP emerged as potentially important regulators of the bacterial populations in the infant gut. The study demonstrates the utility of biomarker and bacteria profiling from daily stool samples for analysing in vivo associations between the immune system and the gut microbiota and provides evidence of host regulation of the microbiota in infants.

Keywords: IAP; Infant gut microbiome; albumin; immune biomarkers; lipocalin 2; mucin.

Figure 1

Intercorrelations between faecal biomarker concentrations, lower left triangle, and daily changes (delta), upper right triangle, (A) at 6 months and (B) at 12 months. P-values are indicated as asterisks: P < 0.001^***; P < 0.1^**; P < 0.5^*.

Figure 2

Gut microbes predicting faecal biomarker changes after adjustment for total protein and total bacteria change. Associations between daily faecal biomarker changes and daily changes in gut microbe abundances at genus levels at (A) 6 months and (B) 12 months of age. The colour represents the strength of association from a linear mixed model adjusting for total protein and total bacterial abundance changes. P-values are indicated as asterisks: P < 0.001^***; P < 0.1^**; P < 0.5^*. The microbial class is presented as the sidebar colour.

Figure 3

Biomarker levels predicting gut microbe changes. Associations between faecal biomarker concentrations and daily changes in gut microbe abundances at the family and genus levels at (A) 6 months and (B) 12 months of age. The colour represents the strength of association from a linear mixed model adjusting for total protein concentration. P-values are indicated as asterisks: P < 0.001^***; P < 0.1^**; P < 0.5^*. The microbial class is presented as the sidebar colour.