Developmental Stage, Solid Food Introduction, and Suckling Cessation Differentially Influence the Comaturation of the Gut Microbiota and Intestinal Epithelium in Rabbits.

BACKGROUND: In mammals, the establishment around weaning of a symbiotic relationship between the gut microbiota and its host determines long-term health. OBJECTIVES: The aim of this study was to identify the factors driving the comaturation of the gut microbiota and intestinal epithelium at the suckling-to-weaning transition. We hypothesized that the developmental stage, solid food ingestion, and suckling cessation contribute to this process. METHODS: From birth to day 18, Hyplus rabbits were exclusively suckling. From day 18 to day 25, rabbits were 1) exclusively suckling; 2) suckling and ingesting solid food; or 3) exclusively ingesting solid food. The microbiota (16S amplicon sequencing), metabolome (nuclear magnetic resonance), and epithelial gene expression (high-throughput qPCR) were analyzed in the cecum at days 18 and 25. RESULTS: The microbiota structure and metabolic activity were modified with age when rabbits remained exclusively suckling. The epithelial gene expression of nutrient transporters, proliferation markers, and innate immune factors were also regulated with age (e.g., 1.5-fold decrease of TLR5). Solid food ingestion by suckling rabbits had a major effect on the gut microbiota by increasing its α diversity, remodeling its structure (e.g., 6.3-fold increase of Ruminococcaceae), and metabolic activity (e.g., 4.6-fold increase of butyrate). Solid food introduction also regulated the gene expression of nutrient transporters, differentiation markers, and innate immune factors in the epithelium (e.g., 3-fold increase of nitric oxide synthase). Suckling cessation had no effect on the microbiota, while it regulated the expression of genes involved in epithelial differentiation and immunoglobulin transport (e.g., 2.5-increase of the polymeric immunoglobulin receptor). CONCLUSIONS: In rabbits, the maturation of the microbiota at the suckling-to-weaning transition is driven by the introduction of solid food and, to a lesser extent, by the developmental stage. In contrast, the maturation of the intestinal epithelium at the suckling-to-weaning transition is under the influence of the developmental stage, solid food introduction, and suckling cessation.

Effect of diet supplemented with functional amino acids and polyphenols on gut health in broilers subjected to a corticosterone-induced stress.

To address the overuse of antimicrobials in poultry production, new functional feed ingredients, i.e. ingredients with benefits beyond meeting basic nutritional requirements, can play a crucial role thanks to their prophylactic effects. This study evaluated the effects of the supplementation of arginine, threonine and glutamine together with grape polyphenols on the gut integrity and functionality of broilers facing a stress condition. 108 straight-run newly hatched Ross PM3 chicks were kept until 35 days and were allocated to 3 treatments. Broilers in the control group were raised in standard conditions. In experimental groups, birds were administered with corticosterone in drinking water (CORT groups) to impair the global health of the animal and were fed a well-balanced diet supplemented or not with a mix of functional amino acids together with grape extracts (1 g/kg of diet-CORT + MIX group). Gut permeability was significantly increased by corticosterone in non-supplemented birds. This corticosterone-induced stress effect was alleviated in the CORT + MIX group. MIX supplementation attenuated the reduction of crypt depth induced by corticosterone. Mucin 2 and TNF-α gene expression was up-regulated in the CORT + MIX group compared to the CORT group. Caecal microbiota remained similar between the groups. These findings indicate that a balanced diet supplemented with functional AA and polyphenols can help to restore broiler intestinal barrier after a stress exposure.

A multi-omics dataset of the response to early plant polysaccharide ingestion in rabbits.

The transition from a milk-based diet to exclusive solid feeding deeply modifies microbiota-host crosstalk. Specifically, early ingestion of plant polysaccharides would be one of the main nutritional components to drive host-microbiota-interaction. To capture the effects of polysaccharides early-life nutrition (starch vs rapidly fermentable fiber) on the holobiont development, we investigated on the one hand the gut bacteriome and metabolome and on the other hand the transcriptome of two host gut tissues. Rabbit model was used to study post-natal co-development of the gut microbiota and its host around weaning transition. The assessment of the microbial composition of the gut appendix together with the caecum was provided for the first time. Gene expression signatures were analyzed along the gut (ileum and caecum) through high-throughput qPCR. The data collected were completed by the analysis of animal growth changes and time-series assessment of blood biomarkers. Those accessible and reusable data could help highlight the gut development dynamics as well as biological adaptation processes at the onset of solid feeding.

Early Introduction of Plant Polysaccharides Drives the Establishment of Rabbit Gut Bacterial Ecosystems and the Acquisition of Microbial Functions.

In mammals, the introduction of solid food is pivotal for the establishment of the gut microbiota. However, the effects of the first food consumed on long-term microbiota trajectory and host response are still largely unknown. This study aimed to investigate the influences of (i) the timing of first solid food ingestion and (ii) the consumption of plant polysaccharides on bacterial community dynamics and host physiology using a rabbit model. To modulate the first exposure to solid nutrients, solid food was provided to suckling rabbits from two different time points (3 or 15 days of age). In parallel, food type was modulated with the provision of diets differing in carbohydrate content throughout life: the food either was formulated with a high proportion of rapidly fermentable fibers (RFF) or was starch-enriched. We found that access to solid food as of 3 days of age accelerated the gut microbiota maturation. Our data revealed differential effects according to the digestive segment: precocious solid food ingestion influenced to a greater extent the development of bacterial communities of the appendix vermiformis, whereas life course polysaccharides ingestion had marked effects on the cecal microbiota. Greater ingestion of RFF was assumed to promote pectin degradation as revealed by metabolomics analysis. However, transcriptomic and phenotypic host responses remained moderately affected by experimental treatments, suggesting little outcomes of the observed microbiome modulations on healthy subjects. In conclusion, our work highlighted the timing of solid food introduction and plant polysaccharides ingestion as two different tools to modulate microbiota implantation and functionality. IMPORTANCE Our study was designed to gain a better understanding of how different feeding patterns affect the dynamics of gut microbiomes and microbe-host interactions. This research showed that the timing of solid food introduction is a key component of the gut microbiota shaping in early developmental stages, though with lower impact on settled gut microbiota profiles in older individuals. This study also provided in-depth analysis of dietary polysaccharide effects on intestinal microbiota. The type of plant polysaccharides reaching the gut through the lifetime was described as an important modulator of the cecal microbiome and its activity. These findings will contribute to better define the interventions that can be employed for modulating the ecological succession of young mammal gut microbiota.

Data set on early feed intake and growth performances of rabbits fed during the suckling period with pellets differing in diameter or compression rate using a double-choice testing design.

Weaning is a critical period for the health of rabbits, with a high sensitivity to digestive diseases. Allowing early consumption of solid feed in the nest of the suckling rabbit could help to maintain its health around weaning. In general, previous studies have focused on feed intake of rabbits when they are able to leave the nest, i.e. around 16 days. Herein, we provide a unique dataset of the dynamics of the onset of feed intake in suckling rabbits from 8 days to weaning. We quantified the solid feed intake behaviour and determined the dietary preferences for pellets according to their physical properties using nine pellets differing in diameter or compression rate. Additionally to the data provided in Paës et al. [1] we provide (i) the description of the nine pellets processing (ii) the description of the 3 point-scale system for nest quality evaluation, (iii) details on the device used to provide pellets in the nest, (iv) milk intake data and milk intake curve calculation and (v) pellet intake data according to physical characteristics.

Gut microbiota derived metabolites contribute to intestinal barrier maturation at the suckling-to-weaning transition.

In suckling mammals, the onset of solid food ingestion is coincident with the maturation of the gut barrier. This ontogenic process is driven by the colonization of the intestine by the microbiota. However, the mechanisms underlying the microbial regulation of the intestinal development in early life are not fully understood. Here, we studied the co-maturation of the microbiota (composition and metabolic activity) and of the gut barrier at the suckling-to-weaning transition by using a combination of experiments in vivo (suckling rabbit model), ex vivo (Ussing chambers) and in vitro (epithelial cell lines and organoids). The microbiota composition, its metabolic activity, para-cellular epithelial permeability and the gene expression of key components of the gut barrier shifted sharply at the onset of solid food ingestion in vivo, despite milk was still predominant in the diet at that time. We found that cecal content sterile supernatant (i.e. containing a mixture of metabolites) obtained after the onset of solid food ingestion accelerated the formation of the epithelial barrier in Caco-2 cells in vitro and our results suggested that these effects were driven by the bacterial metabolite butyrate. Moreover, the treatment of organoids with cecal content sterile supernatant partially replicated in vitro the effects of solid food ingestion on the epithelial barrier in vivo. Altogether, our results show that the metabolites produced by the microbiota at the onset of solid food ingestion contribute to the maturation of the gut barrier at the suckling-to-weaning transition. Targeting the gut microbiota metabolic activity during this key developmental window might therefore be a promising strategy to promote intestinal homeostasis.

Early Introduction of Solid Feeds: Ingestion Level Matters More Than Prebiotic Supplementation for Shaping Gut Microbiota.

Early introduction of a nutritional substrate is a promising biomimetic strategy for controlling the implantation of the microbiota and preserving the health of young animals. In this study, we provided experimental solid substrate in a gel form to stimulate suckling rabbits' intake and to investigate its effects on microbiota implantation and colonization. All the rabbits had access to solid feed outside the nest as of 15 days of age. Except for the control group, rabbits were offered starter feed gels inside the nests from 3 to 18 days of age. These gels were either free of additives (AF_GEL) or contained 4% of fructo-oligosaccharides (FOS_GEL) or 4% of mannan-oligosaccharides and ß-glucans mixtures (MOS_GEL). The cecal content of 160 rabbits was sampled at 18, 29, 38, and 57 days of age and analyzed using 16S rRNA gene sequencing. Pups consumed an average of 3.95 ± 1.07 g of starter feed gel with a higher intake when it was supplemented with fructo-oligosaccharides (+1.2 g; P < 0.05). Starter feed gel consumption increased the ensuing intake of pellets (+17 g from 15 to 21 days; P < 0.05). Alpha-diversity indexes were similar between groups and prebiotic supplementation did not induce a clear shift in microbiota pattern. Conversely, when considering rabbits that consumed more starter feed, the highest proportions of bacteria with plant-degrading abilities, such as species from the Lachnospiraceae and Ruminococcaceae families, were observed at 18 days of age. However, fermentative activities were not affected by starter feed intake at 29, 38, and 57 days of age. By providing comprehensive results on the regulation of microbial community structure at the onset of solid feed intake, this research paves the way for further studies on digestive ecosystem maturation.