Neonatal Consumption of Oligosaccharides Greatly Increases L-Cell Density without Significant Consequence for Adult Eating Behavior

Abstract

Oligosaccharides (OS) are commonly added to infant formulas, however, their physiological impact, particularly on adult health programming, is poorly described. In adult animals, OS modify microbiota and stimulate colonic fermentation and enteroendocrine cell (EEC) activity. Since neonatal changes in microbiota and/or EEC density could be long-lasting and EEC-derived peptides do regulate short-term food intake, we hypothesized that neonatal OS consumption could modulate early EECs, with possible consequences for adult eating behavior. Suckling rats were supplemented with fructo-oligosaccharides (FOS), beta-galacto-oligosaccharides/inulin (GOS/In) mix, alpha-galacto-oligosaccharides (αGOS) at 3.2 g/kg, or a control solution (CTL) between postnatal day (PND) 5 and 14/15. Pups were either sacrificed at PND14/15 or weaned at PND21 onto standard chow. The effects on both microbiota and EEC were characterized at PND14/15, and eating behavior at adulthood. Very early OS supplementation drastically impacted the intestinal environment, endocrine lineage proliferation/differentiation particularly in the ileum, and the density of GLP-1 cells and production of satiety-related peptides (GLP-1 and PYY) in the neonatal period. However, it failed to induce any significant lasting changes on intestinal microbiota, enteropeptide secretion or eating behavior later in life. Overall, the results did not demonstrate any OS programming effect on satiety peptides secreted by L-cells or on food consumption, an observation which is a reassuring outlook from a human perspective.

Maternal Microbiota Transfer Programs Offspring Eating Behavior

“…Based on the longitudinal follow-up we performed, using feces collected at PND60 and PND130 ( Supplementary Figures 4A–D ), the microbiotal differences between transferred and control animals were minimal as early as PND60. This fading overtime was already observed in our earlier studies using neonatal prebiotic supplementations to induce early microbiological changes (i.e., prior to full weaning) ( Morel et al, 2015 ; Le Drean et al, 2019 ). Our manipulations of the microbiota composition might in fact have been applied too early as they were stopped before weaning, a time when intestinal microbiota is described as unstable ( Schloss et al, 2012 ) as a result of the change in the nature of the food consumed (see Laforest-Lapointe and Arrieta, 2017 for a review).…”

“…Between PND137 and PND155, eating behavior was analyzed in physiological cages (Phecomb cages, Bioseb, Vitrol, France), as previously described ( Coupe et al, 2011 ; Le Drean et al, 2019 ). Briefly, rats were allowed to adapt individually to physiological cage during 1 day before data recording.…”

Bioregional Alterations in Gut Microbiome Contribute to the Plasma Metabolomic Changes in Pigs Fed with Inulin

“…Inulin influences directly on the gut, including prebiotic effects, improvement of bowel function and glycolipid metabolism in the host, secretion of satiety hormone and increased short fatty acids (SCFAs) production [5][6][7][8]. Although the exact mechanism has not been elucidated, the gut microbiota has been considered as a potential modulating factor [9].…”

In Vitro Evaluation of the Effects of Commercial Prebiotic GOS and FOS Products on Human Colonic Caco–2 Cells

“…Dietary supplementation of GOS has also been linked with improvements in the transition to a mature intestinal microbiota in broiler chickens [12,15] and in suckling piglets [16,17]. In a study conducted with suckling male rats, in addition to changes in the intestinal microbiota, Le Dréan et al [18] observed GOS and FOS supplementation impacted entero-endocrine cell maturation by bringing about transient increases in the density of GLP-1 cells and the production of the satiety-related peptides GLP-1 and PYY.…”