Sophie Blat

Breast- v. formula-feeding: impacts on the digestive tract and immediate and long-term health effects

The health benefits of breast-feeding have been recognised for a long time. In particular, breast-feeding is associated with lower incidence of necrotising enterocolitis and diarrhoea during the early period of life and with lower incidence of inflammatory bowel diseases, type 2 diabetes and obesity later in life. The higher nutritional and protective degree of human milk is related to its nutritional composition that changes over the lactation period and to the biological activities of specific components while lower growth rate of breast-fed infants may be attributed to their self-regulation of milk intake at a lower level than formula-fed infants. Many results now suggest that the developmental changes in intestinal and pancreatic function that occur postnatally are modulated by the diet. Indeed, formula-feeding induces intestinal hypertrophy and accelerates maturation of hydrolysis capacities; it increases intestinal permeability and bacterial translocation, but does not induce evident differences in microbiota composition. Whether these changes would be beneficial for enhancing absorptive capacities and for educating the gut-associated immune system remains to be further studied. Moreover, it is evident that formula-feeding increases basal blood glucose and decreases plasma ketone body concentrations, while discrepancies on postprandial glycaemia, insulin and incretin responses in both human studies and experimental studies are inconclusive. Manipulating the composition of formula, by reducing protein content, adding prebiotics, growth factors or secretory IgA can modulate intestinal and pancreatic function development, and thereby may reduce the differential responses between breast-fed and formula-fed neonates. However, the developmental responses of the digestive tract to different feeding strategies must be elucidated in terms of sensitivity to developing diseases, taking into account the major role of the intestinal microbiota.

A computed tomography scan application to evaluate adiposity in a minipig model of human obesity

The aim of the present study was to describe and validate a computed tomography (CT) method to analyse adiposity distribution in Göttingen minipigs. Adiposity was evaluated in two groups of minipigs. In group 1 (n 8), measurements were performed before and after the induction of obesity. In group 2 (n 7), animals were fed rations designed to obtain heterogeneous adiposity before analyses. CT acquisitions were associated with anatomical, ultrasonography and body chemical measurements. Our CT method was based on acquisition of a single slice at a fixed anatomical landmark, calculation of individual X-ray density ranges for CT values and delineation of the three main adipose compartments (subcutaneous adipose tissue, SAT; retroperitoneal adipose tissue, RAT; and visceral adipose tissue, VAT). Our validation measures showed that the CT-scan method was accurate, sensitive and reliable. The CT data were found to be correlated with body weight, abdominal perimeter, ultrasonography, anatomical measurements and body chemical composition (from r 0.84 to 0.93, P < 0.001 for all), with a pitfall concerning the precise estimation of VAT. With increased body weight, the amount of adipose tissue increased and the relative proportion of SAT increased, whereas the relative proportion of RAT and VAT decreased (P < 0.001 for all). Adiposity measured by CT, and especially SAT, was found to be negatively correlated with insulin sensitivity (r 0.54, P < 0.05). In conclusion, a precise evaluation of the adipose compartments in minipigs was done by CT. Therefore, the use of Göttingen minipigs is relevant to further investigate the relationship between the different adipose tissues and obesity.

Role of vagal innervation on intragastric distribution and emptying of liquid and semisolid meals in conscious pigs.

The role of vagal innervation on emptying patterns and intragastric distributions of liquid and semisolid meals is still controversial. We aimed to record these features after dorsal, ventral and truncal vagotomies, using external gamma scintigraphy in conscious pigs in which the dorsal vagus specifically innervates the proximal stomach. Imaging of the stomach was performed for all experimental situations and before surgery using 99mTc‐labelled glucose and porridge meals. Emptying of liquids was faster after dorsal vagotomy, whereas it was unchanged after ventral and truncal vagotomies (T1/2=57 ± 8.5, 31 ± 14.4, 54 ± 9.1 and 42 ± 14.9 min for intact, dorsal, ventral and truncal vagotomies, respectively). On the other hand, truncal vagotomy significantly reduced the emptying rate of semisolids whereas dorsal and ventral vagotomies had no significant effect (T1/2=96 ± 7.2, 113 ± 8.1, 75 ± 9.9 and 260 ± 56.6 min for intact, dorsal, ventral and truncal vagotomies). Morphological analysis of the gastric shape confirmed an overdistended proximal stomach after truncal vagotomy only. For semisolids, proximal stomach emptying followed the same emptying pattern as the entire stomach, irrespective of the surgical procedure. We concluded that the proximal stomach is the main control for the emptying of liquids and semisolids. The vagal control of overall gastric emptying for semisolids is probably identical to that modulating the intragastric distribution of the meal.

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 TGFβ1 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 Peyers 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 TGFβ1 concentrations tended to improve (P<0.1). IFNγ secretion by stimulated Peyers patch and mesenteric lymph node cells, and secretory IgA production by unstimulated Peyers 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.

A maternal Western diet during gestation and lactation modifies offspring’s microbiota activity, blood lipid levels, cognitive responses, and hippocampal neurogenesis in Yucatan pigs

A suboptimal early nutritional environment (i.e., excess of energy, sugar, and fat intake) can increase susceptibility to diseases and neurocognitive disorders. The purpose of this study was to investigate in nonobese Yucatan minipigs (Sus scrofa) the impact of maternal diet [standard diet (SD) vs. Western diet (WD)] during gestation and 25 d of lactation on milk composition, blood metabolism, and microbiota activity of sows (n = 17) and their piglets (n = 65), and on spatial cognition (n = 51), hippocampal plasticity (n = 17), and food preferences/motivation (n = 51) in the progeny. Milk dry matter and lipid content, as well as plasma total cholesterol and free fatty acid (FFA) concentrations (P < 0.05) were higher in WD than in SD sows. Microbiota activity decreased in both WD sows and 100‐d‐old piglets (P < 0.05 or P < 0.10, depending on short‐chain FAs [SCFAs]). At weaning [postnatal day (PND) 25], WD piglets had increased blood triglyceride and FFA levels (P < 0.01). Both SD and WD piglets consumed more of a known SD than an unknown high‐fat and ‐sucrose (HFS) diet (P < 0.0001), but were quicker to obtain HFS rewards compared with SD rewards (P < 0.01). WD piglets had higher working memory (P = 0.015) and reference memory (P < 0.001) scores, which may reflect better cognitive abilities in the task context and a higher motivation for the food rewards. WD piglets had a smaller hippocampal granular cell layer (P = 0.03) and decreased neurogenesis (P < 0.005), but increased cell proliferation (P < 0.001). A maternal WD during gestation and lactation, even in the absence of obesity, has significant consequences for piglets’ blood lipid levels, microbiota activity, gut–brain axis, and neurocognitive abilities after weaning.—Val‐Laillet, D., Besson, M., Guérin, S., Coquery, N., Randuineau, G., Kanzari, A., Quesnel, H., Bonhomme, N., Bolhuis, J. E., Kemp, B., Blat, S., Le Huërou‐Luron, I., Clouard, C. A maternal Western diet during gestation and lactation modifies offsprings microbiota activity, blood lipid levels, cognitive responses, and hippocampal neurogenesis in Yucatan pigs. FASEB J. 31, 2037–2049 (2017). www.fasebj.org

The vagus is inhibitory of the late postprandial insulin secretion in conscious pigs

The vagus is involved in the cephalic phase of insulin secretion but its role in the meal absorption phase of insulin release remains to be defined. The aim of this study was therefore to evaluate the role of the vagus in the early and the late meal absorption phases of insulin secretion. In six pigs, venous insulin profiles were compared in intact animals, after ventral or dorsal vagal trunk section, and after section of both vagal trunks (truncal vagotomy). Since gastric emptying could be modified by vagotomy, it was recorded concomitantly by gamma scintigraphy. Semi-solid (porridge) and liquid (glucose 10%) meals were tested. Truncal vagotomy significantly increased insulin release compare to intact animals after glucose (63.8%) and porridge (174.4%) meals in the early and the late absorption phases of insulin secretion, respectively. For the glucose meal, this effect could be explained by a vagally mediated change in gastric emptying rate, since insulin concentrations for a similar amount of nutrient propelled to the duodenum were not different in intact and truncal vagotomized animals. In contrast, after the porridge meal, truncal vagotomy was associated with a second, later occurring increase in circulating insulin, which could not be explained by changes in gastric emptying rate. These results demonstrate for the first time an inhibitory role of the vagus in the late meal absorption phase of insulin release.

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.

Dietary α‐lactalbumin supplementation alleviates normocaloric western diet‐induced glucose intolerance in Göttingen minipigs

The pandemic of obesity in Western countries is mainly due to the high‐fat, high‐energy diet prevailing there. Obesity‐associated metabolic disorders are the consequence of fat mass increase leading to altered adipokine secretion, hyperlipemia, oxidant stress, low‐grade inflammation, and eventually glucose intolerance. Yet not all people consuming a Western diet become obese, and the question is raised whether these people are also at risk of developing metabolic disorders.