Maternal short chain fructo-oligosaccharides supplementation during late gestation and lactation influences milk components and offspring gut metabolome: a pilot study.

Breast milk composition is influenced by maternal diet. This study aimed to evaluate if supplementation of maternal diet with a prebiotic fibre, through its potential effect on milk composition, can be a leverage to orientate the gut microbiota of infants in a way that would be beneficial for their health. Twelve sows received a diet supplemented with short chain fructo-oligosaccharides or maltodextrins during the last month of gestation and the lactation. Oligosaccharidic and lipidomic profiles of colostrum and mature milk (21 days), as well as faecal microbiota composition and metabolomic profile of 21 day-old piglets were evaluated. The total porcine milk oligosaccharide concentration tended to be lower in scFOS-supplemented sows, mainly due to the significant reduction of the neutral core oligosaccharides (in particular that of a tetrahexose). Maternal scFOS supplementation affected the concentration of 31 lipids (mainly long-chain triglycerides) in mature milk. Faecal short-chain fatty acid content and that of 16 bacterial metabolites were modified by scFOS supplementation. Interestingly, the integrative data analysis gave a novel insight into the relationships between (i) maternal milk lipids and PMOs and (ii) offspring faecal bacteria and metabolites. In conclusion, scFOS-enriched maternal diet affected the composition of mature milk, and this was associated with a change in the colonisation of the offspring intestinal microbiota.

Gastrointestinal Tolerance of Short-Chain Fructo-Oligosaccharides from Sugar Beet: An Observational, Connected, Dose-Ranging Study in Healthy Volunteers.

Dietary fibres are important in the human diet with multiple health benefits. This study aimed to determine the gastrointestinal tolerance of short-chain fructo-oligosaccharides (scFOS), well-known prebiotic fibres, at doses up to 40 g/d. An observational, connected, dose-ranging trial was conducted in 116 healthy volunteers. During the first week, the participants were instructed to consume their usual diet. During the second week, half of the subjects consumed 15 g scFOS per day, and the other half consumed 20 g scFOS per day. For the third week, the scFOS dose was doubled for all subjects. Gastrointestinal symptom severity was reported daily, as well as stool consistency and frequency. The results show that scFOS are well tolerated up to 40 g/d; all reported symptoms remained very mild from a clinical perspective. Stool consistency stayed normal, between 3 and 5 on the Bristol stool scale, confirming that no diarrhoea appeared after scFOS intake. Stool frequency also remained within the normal range. In conclusion, scFOS intake is well tolerated up to 40 g/d in healthy subjects. Thanks to their short chains and unique composition, scFOS prebiotic fibres are much better tolerated than other types of inulin-type fructans with longer chains. The digestive tolerance of fibres should be considered when added to foods and beverages.

Maternal Supplementation of Food Ingredient (Prebiotic) or Food Contaminant (Mycotoxin) Influences Mucosal Immune System in Piglets.

The early life period is crucial for the maturation of the intestinal barrier, its immune system, and a life-long beneficial host-microbiota interaction. The study aims to assess the impact of a beneficial dietary (short-chain fructooligosaccharides, scFOS) supplementation vs. a detrimental dietary environment (such as mycotoxin deoxynivalenol, DON) on offspring intestinal immune system developmental profiles. Sows were given scFOS-supplemented or DON-contaminated diets during the last 4 weeks of gestation, whereas force-feeding piglets with DON was performed during the first week of offspring life. Intestinal antigen-presenting cell (APC) subset frequency was analyzed by flow cytometry in the Peyer's patches and in lamina propria and the responsiveness of intestinal explants to toll-like receptor (TLR) ligands was performed using ELISA and qRT-PCR from post-natal day (PND) 10 until PND90. Perinatal exposure with scFOS did not affect the ontogenesis of APC. While it early induced inflammatory responses in piglets, scFOS further promoted the T regulatory response after TLR activation. Sow and piglet DON contamination decreased CD16+ MHCII+ APC at PND10 in lamina propria associated with IFNγ inflammation and impairment of Treg response. Our study demonstrated that maternal prebiotic supplementation and mycotoxin contamination can modulate the mucosal immune system responsiveness of offspring through different pathways.

Short-chain fructo-oligosaccharides supplementation to suckling piglets: Assessment of pre- and post-weaning performance and gut health.

Farmers face difficulties in redeeming their investment in larger litter sizes since this comes with larger litter heterogenicity, lower litter resilience and risk of higher mortality. Dietary oligosaccharides, given to the sow, proved beneficial for the offspring's performance. However, giving oligosaccharides to the suckling piglet is poorly explored. Therefore, this field trial studied the effect of dietary short-chain fructo-oligosaccharides (scFOS; 1g/day; drenched) supplementation to low (LBW, lower quartile), normal (NBW, two intermediate quartiles) and high (HBW, upper quartile) birth weight piglets from birth until 7 or 21 days of age. Performance parameters, gut microbiome and short-chain fatty acids profile of feces and digesta were assessed at birth (d 0), d 7, weaning (d 21.5) and 2 weeks post-weaning (d 36.5). Additional parameters reflecting gut health (intestinal integrity and morphology, mucosal immune system) were analysed at d 36.5. Most parameters changed with age or differed with the piglet's birth weight. Drenching with scFOS increased body weight by 1 kg in NBW suckling piglets and reduced the post-weaning mortality rate by a 100%. No clear difference in the IgG level, the microbiota composition and fermentative activity between the treatment groups was observed. Additionnally, intestinal integrity, determined by measuring intestinal permeability and regenerative capacity, was similar between the treatment groups. Also, intestinal architecture (villus lenght, crypt depth) was not affected by scFOS supplementation. The density of intra-epithelial lymphocytes and the expression profiles (real-time qPCR) for immune system-related genes (IL-10, IL-1ß, IL-6, TNFα and IFNγ) were used to assess mucosal immunity. Only IFNγ expression, was upregulated in piglets that received scFOS for 7 days. The improved body weight and the reduced post-weaning mortality seen in piglets supplemented with scFOS support the view that scFOS positively impact piglet's health and resilience. However, the modes of action for these effects are not yet fully elucidated and its potential to improve other performance parameters needs further investigation.

Effects of ß-Fructans Fiber on Bowel Function: A Systematic Review and Meta-Analysis.

The aim of this systematic review and meta-analysis was to assess the effects of ß-fructan supplementation on bowel function in healthy volunteers and patients. The search process was based on the selection of publications listed in the Pubmed and EUPMC database until December 2017, plus two unpublished studies, to identify studies evaluating the impact of ß-fructans on bowel movement and stool parameters. Forty-seven publications were selected for inclusion. Primary parameter was frequency of bowel movements, evaluated by the number of defecations per day during the study period. Secondary outcomes were stool consistency, stool dry and wet weights, and transit time. Short-chain (DP < 10) ß-fructans contributed to increased stool frequency (0.36 defecation +/- 0.06 per day; p < 0.001), while no significant effect was reported with long-chain (DP ≥ 10) ß-fructans (-0.03 +/- 0.11, p = 0.82). A minimal increase in stool wet weight was also statistically demonstrated with short-chain ß-fructans. Moreover, the meta-analysis highlighted significant differences in stool consistency in contrast to fecal dry weight after ß-fructan supplementation. This systematic review and meta-analysis indicates that short-chain ß-fructan supplementation has a positive effect on bowel function by significantly increasing the frequency of bowel movements.

Perinatal short-chain fructooligosaccharides program intestinal microbiota and improve enteroinsular axis function and inflammatory status in high-fat diet-fed adult pigs.

Perinatal nutrition programs physiologic and metabolic functions, with consequences on the susceptibility to develop metabolic diseases in adulthood. The microbiota represents a key factor of such programming. We investigated whether perinatal prebiotic [short-chain fructooligosaccharides (scFOS)] supplementation improved adult metabolic health in association with microbiota changes in pigs used as human model. Sows were supplemented with scFOS or not during the end of gestation and the entire lactation, and offspring received scFOS accordingly during 1 mo after weaning. Pigs were then fed a standard diet for 5 mo, followed by a high-fat diet for 3 mo once adults. Perinatal scFOS supplementation induced a persistent modulation of the composition of the fecal microbiota in adulthood, notably by increasing the Prevotella genus. Meanwhile, scFOS animals displayed improved capacity to secrete glucagon-like peptide-1 and improved pancreas sensitivity to glucose without any changes in peripheral insulin sensitivity. Perinatal scFOS supplementation also increased ileal secretory IgA secretion and alkaline phosphatase activity and decreased TNF-α expression in adipose tissue. In conclusion, perinatal scFOS supplementation induced long-lasting modulation of intestinal microbiota and had beneficial consequences on the host physiology in adulthood. Our results highlight the key role of perinatal nutrition on later microbiota and host metabolic adaptation to an unbalanced diet.-Le Bourgot, C., Ferret-Bernard, S., Apper, E., Taminiau, B., Cahu, A., Le Normand, L., Respondek, F., Le Huërou-Luron, I., Blat, S. Perinatal short-chain fructooligosaccharides program intestinal microbiota and improve enteroinsular axis function and inflammatory status in high-fat diet-fed adult pigs.

A mixture of milk and vegetable lipids in infant formula changes gut digestion, mucosal immunity and microbiota composition in neonatal piglets.

PURPOSE: Although composition of infant formula has been significantly improved during the last decade, major differences with the composition and structure of breast milk still remain and might affect nutrient digestion and gut biology. We hypothesized that the incorporation of dairy fat in infant formulas could modify their physiological impacts by making their composition closer to that of human milk. The effect of milk fat and milk fat globule membrane (MFGM) fragments in infant formulas on gut digestion, mucosal immunity and microbiota composition was evaluated. METHODS: Three formulas containing either (1) vegetable lipids stabilized only by proteins (V-P), (2) vegetable lipids stabilized by a mixture of proteins and MFGM fragments (V-M) and (3) a mixture of milk and vegetable lipids stabilized by a mixture of proteins and MFGM fragments (M-M) were automatically distributed to 42 newborn piglets until slaughter at postnatal day (PND) 7 or 28, and compared to a fourth group of sow's suckling piglets (SM) used as a breast-fed reference. RESULTS: At both PND, casein and ß-lactoglobulin digestion was reduced in M-M proximal jejunum and ileum contents compared to V-P and V-M ones leading to more numerous ß-Cn peptides in M-M contents. The IFNγ cytokine secretion of ConA-stimulated MLN cells from M-M piglets tended to be higher than in V-P ones at PND 7 and PND 28 and was closer to that of SM piglets. No dietary treatment effect was observed on IL-10 MLN cell secretion. Changes in faecal microbiota in M-M piglets resulted in an increase in Proteobacteria and Bacteroidetes and a decrease in Firmicutes phyla compared to V-P ones. M-M piglets showed higher abundances of Parabacteroides, Escherichia/Shigella and Klebsiella genus. CONCLUSIONS: The incorporation of both milk fat and MFGM fragments in infant formula modifies protein digestion, the dynamic of the immune system maturation and the faecal microbiota composition.

Maternal short-chain fructo-oligosaccharide supplementation increases intestinal cytokine secretion, goblet cell number, butyrate concentration and Lawsonia intracellularis humoral vaccine response in weaned pigs.

Prebiotic supplementation modulates immune system development and function. However, less is known about the effects of maternal prebiotic consumption on offspring intestinal defences and immune system responsiveness. We investigated the effects of maternal short-chain fructo-oligosaccharide (scFOS) supplementation on mucin-secreting cells, ileal secretory IgA and cytokine secretion of weaned offspring and their humoral response to an oral vaccine against obligate intracellular Lawsonia intracellularis. Sows were fed a control diet (CTRL) or scFOS-supplemented diet during the last third of gestation and throughout lactation. At weaning, each litter was divided into two groups receiving a post-weaning CTRL or scFOS diet for a month. Pigs from the four groups were either non-vaccinated (n 16) or vaccinated (n 117) at day 33. Biomarkers related to intestinal defences and immune parameters were analysed 3 weeks later. SCFA production was assessed over time in suckling and weaned pigs. Maternal scFOS supplementation improved ileal cytokine secretions (interferon (IFN)-γ, P<0·05; IL-4, P=0·07) and tended to increase caecal goblet cell number (P=0·06). It increased IgA vaccine response in the serum (P<0·01) and ileal mucosa (P=0·08). Higher bacterial fermentative activity was observed during lactation (total faecal SCFA, P<0·001) and after weaning (colonic butyrate, P=0·10) in pigs from scFOS-supplemented mothers. No synergistic effect between maternal and post-weaning scFOS supplementation was observed. Therefore, maternal scFOS supplementation has long-lasting consequences by strengthening gut defences and immune response to a vaccine against an intestinal obligate intracellular pathogen. Prebiotic consumption by gestating and lactating mothers is decisive in modulating offspring intestinal immunity.

Maternal short-chain fructooligosaccharide supplementation influences intestinal immune system maturation in piglets.

Peripartum nutrition is crucial for developing the immune system of neonates. We hypothesized that maternal short-chain fructooligosaccharide (scFOS) supplementation could accelerate the development of intestinal immunity in offspring. Thirty-four sows received a standard or a scFOS supplemented diet (10 g scFOS/d) for the last 4 weeks of gestation and the 4 weeks of lactation. Colostrum and milk immunoglobulins (Ig) and TGFß1 concentrations were evaluated on the day of delivery and at d 6 and d 21 postpartum. Piglet intestinal structure, the immunologic features of jejunal and ileal Peyer's patches, and mesenteric lymph node cells were analysed at postnatal d 21. Short-chain fatty acid concentrations were measured over time in the intestinal contents of suckling and weaned piglets. Colostral IgA (P<0.05) significantly increased because of scFOS and TGFß1 concentrations tended to improve (P<0.1). IFNγ secretion by stimulated Peyer's patch and mesenteric lymph node cells, and secretory IgA production by unstimulated Peyer's patch cells were increased (P<0.05) in postnatal d 21 scFOS piglets. These differences were associated with a higher proportion of activated CD25+CD4α+ T cells among the CD4+ helper T lymphocytes (P<0.05) as assessed by flow cytometry. IFNγ secretion was positively correlated with the population of activated T lymphocytes (P<0.05). Total short-chain fatty acids were unchanged between groups during lactation but were higher in caecal contents of d 90 scFOS piglets (P<0.05); specifically propionate, butyrate and valerate. In conclusion, we demonstrated that maternal scFOS supplementation modified the intestinal immune functions in piglets in association with increased colostral immunity. Such results underline the key role of maternal nutrition in supporting the postnatal development of mucosal immunity.