Abstract
Inflammatory and metabolic diseases can originate during early-life and have been correlated with shifts in intestinal microbial ecology. Here we demonstrate that minor environmental fluctuations during the early neonatal period had sustained effects on the developing porcine microbiota and host-microbe interface. These inter-replicate effects appear to originate during the first day of life, and are likely to reflect very early microbiota acquisition from the environment. We statistically link early systemic inflammation with later local increases in inflammatory cytokine (IL-17) production, which could have important enteric health implications. Immunity, intestinal barrier function, host metabolism and host-microbiota co-metabolism were further modified by Bifidobacterium lactis NCC2818 supplementation, although composition of the in situ microbiota remained unchanged. Finally, our robust model identified novel, strong correlations between urinary metabolites (eg malonate, phenylacetylglycine, alanine) and mucosal immunoglobulin (IgM) and cytokine (IL-10, IL-4) production, thus providing the possibility of the development of urinary ‘dipstick’ tests to assess non-accessible mucosal immune development and identify early precursors (biomarkers) of disease. These results have important implications for infants exposed to neonatal factors including caesarean delivery, antibiotic therapy and delayed discharge from hospital environments, which may predispose to the development of inflammatory and metabolic diseases in later life.
Highlights
Non-communicable diseases associated with metabolism and immunity are an increasing challenge for 21st century medicine
We use the neonatal piglet to evaluate the effect of Bifidobacterium lactis NCC2818 subsp. lactis (B. lactis NCC2818) (CNCM I-3446), previously documented for its probiotic properties in human infants[30,31,32,33,34], on the intestinal microbiota, metabolism and mucosal immune system when supplemented from birth
Supplementation with B. lactis NCC2818 was associated with increased expression of the tight-cell junction (TCJ) associated protein ZO-1 in the epithelium of the distal jejunum (p = 5.7 × 10−5, Fig. 1a, c and e)
Summary
Non-communicable diseases associated with metabolism and immunity are an increasing challenge for 21st century medicine. Predisposition to many of these conditions appears to originate during early-life ‘programming events’[1] This term refers to critical points of developmental plasticity where changes in environmental factors can have long-term effects on physiological development[2, 3]. The existence of these links does suggest that it is feasible to identify biomarkers in accessible biofluids, such as metabolites in urine, which may correlate with changes in less accessible sites, such as immune responses in the intestinal mucosa. Such biomarkers could be effective in the early detection of disease, monitoring disease development and for quantifying the efficacy of therapeutic intervention. We identify immune-metabolic correlations with the aim of exploring potential novel (surrogate) biomarkers in this tractable model species
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