Minimal processed infant formula vs. conventional shows comparable protein quality and increased postprandial plasma amino acid kinetics in rats.

During industrial processing, heat treatments applied to infant formulas may affect protein digestion. Recently, innovative processing routes have been developed to produce minimally heat-processed infant formula. Our objective was to compare the in vivo protein digestion kinetics and protein quality of a minimally processed (T−) and a heat-treated (T+++) infant formula. Sixty-eight male Wistar rats (21 d) were fed with either a diet containing 40 % T− (n 30) or T+++ (n 30), or a milk protein control diet (n 8) during 2 weeks. T− and T+++ rats were then sequentially euthanised 0, 1, 2, 3 or 6 h (n 6/time point) after ingestion of a meal containing their experimental diet. Control rats were euthanised 6 h after ingestion of a protein-free meal to determine nitrogen and amino acid endogenous losses. Nitrogen and amino acid true caecal digestibility was high for both T− and T+++ diets (> 90 %), but a tendency towards higher nitrogen digestibility was observed for the T− diet (96·6 ± 3·1 %) compared with the T+++ diet (91·9 ± 5·4 %, P = 0·0891). This slightly increased digestibility led to a greater increase in total amino acid concentration in plasma after ingestion of the T− diet (P = 0·0010). Comparable protein quality between the two infant formulas was found with a digestible indispensable amino acid score of 0·8. In conclusion, this study showed that minimal processing routes to produce native infant formula do not modify protein quality but tend to enhance its true nitrogen digestibility and increase postprandial plasma amino acid kinetics in rats.

Metabolomics Analysis Reveals the Potential Relationship Between Sow Colostrum and Neonatal Serum Metabolites in Different Pig Breeds.

SCOPE: Colostrum composition is an important indicator of newborn piglet survival and growth. However, limited information is available on the association between colostrum metabolites in sows and serum metabolites in neonates. Therefore, the present study aims to determine the metabolites in the colostrum of sows, in the serum of their offspring piglets, and mother-offspring metabolite correlations in different pig breeds. METHODS AND RESULTS: Colostrum and serum samples are collected from 30 sows and their piglets from three pig breeds (Taoyuan black, TB; Xiangcun black, XB; and Duroc) to analyze the targeted metabolomics. This study identifies 191 metabolites in the colostrum of sows, including fatty acids, amino acids, bile acids, carnitines, carbohydrates, and organic acids, and the concentrations of these metabolites are highest in the TB pigs. Metabolite profiles in sow colostrum and piglet serum differ among Duroc, TB, and XB pigs, and the matching metabolites are mainly enriched in the digestive system and transportation pathways. Furthermore, identification of the associations between metabolites in the colostrum of sows and their neonate sera suggests that metabolite compounds from colostrum are transported to suckling piglets. CONCLUSION: The present study findings deepen the understanding of the composition of sow colostrum metabolites and the transportation of metabolites from sow colostrum to piglets. The findings also provide insight regarding the development of dietary formulas that resemble the sow colostrum for newborn animals to maintain health and improve the early growth of offspring.

Dietary bile acid supplementation in weaned piglets with intrauterine growth retardation improves colonic microbiota, metabolic activity, and epithelial function.

BACKGROUND: Intrauterine growth retardation (IUGR) is one of the major constraints in animal production. Our previous study showed that piglets with IUGR are associated with abnormal bile acid (BA) metabolism. This study explored whether dietary BA supplementation could improve growth performance and colonic development, function, microbiota, and metabolites in the normal birth weight (NBW) and IUGR piglets. A total of 48 weaned piglets (24 IUGR and 24 NBW) were allocated to four groups (12 piglets per group): (i) NBW group, (ii) NBW + BA group, (iii) IUGR group, and (iv) IUGR + BA group. Samples were collected after 28 days of feeding. RESULTS: The results showed that dietary BA supplementation increased the length and weight of the colon and colon weight to body weight ratio, while decreased the plasma diamine oxidase (DAO) concentration in the NBW piglets (P < 0.05). Dietary BA supplementation to IUGR piglets decreased (P < 0.05) the plasma concentrations of D-lactate and endotoxin and colonic DAO and endotoxin, suggesting a beneficial effect on epithelial integrity. Moreover, dietary BA supplementation to NBW and IUGR piglets increased Firmicutes abundance and decreased Bacteroidetes abundance (P < 0.05), whereas Lactobacillus was the dominant genus in the colon. Metabolome analysis revealed 65 and 51 differential metabolites in the colon of piglets fed a diet with/without BA, respectively, which was associated with the colonic function of IUGR piglets. Furthermore, dietary BA supplementation to IUGR piglets upregulated the expressions of CAT, GPX, SOD, Nrf1, IL-2, and IFN-γ in colonic mucosa (P < 0.05). CONCLUSIONS: Collectively, dietary BA supplementation could improve the colonic function of IUGR piglets, which was associated with increasing proportions of potentially beneficial bacteria and metabolites. Furthermore, BA shows a promising application prospect in improving the intestinal ecosystem and health of animals.

Efficiency of Orexin-A for Inflammatory Flare and Mucosal Healing in Experimental Colitis: Comparison with the Anti-TNF Alpha Infliximab.

Inflammatory bowel diseases are chronic inflammation of the intestinal mucosa characterized by relapsing-remitting cycle periods of variable duration. Infliximab (IFX) was the first monoclonal antibody used for the treatment of Crohn's disease and ulcerative colitis (UC). High variability between treated patients and loss of IFX efficiency over time support the further development of drug therapy. An innovative approach has been suggested based on the presence of orexin receptor (OX1R) in the inflamed human epithelium of UC patients. In that context, the aim of this study was to compare, in a mouse model of chemically induced colitis, the efficacy of IFX compared to the hypothalamic peptide orexin-A (OxA). C57BL/6 mice received 3.5% dextran sodium sulfate (DSS) in drinking water for 5 days. Since the inflammatory flare was maximal at day 7, IFX or OxA was administered based on a curative perspective at that time for 4 days using intraperitoneal injection. Treatment with OxA promoted mucosal healing and decreased colonic myeloperoxidase activity, circulating concentrations of lipopolysaccharide-binding protein, IL-6 and tumor necrosis factor alpha (TNFα) and decreased expression of genes encoding cytokines in colonic tissues with better efficacy than IFX allowing for more rapid re-epithelization. This study demonstrates the comparable anti-inflammatory properties of OxA and IFX and shows that OxA is efficient in promoting mucosal healing, suggesting that OxA treatment is a promising new biotherapy.

Amino Acid-Derived Bacterial Metabolites in the Colorectal Luminal Fluid: Effects on Microbial Communication, Metabolism, Physiology, and Growth.

Undigested dietary and endogenous proteins, as well as unabsorbed amino acids, can move from the terminal part of the ileum into the large intestine, where they meet a dense microbial population. Exfoliated cells and mucus released from the large intestine epithelium also supply nitrogenous material to this microbial population. The bacteria in the large intestine luminal fluid release amino acids from the available proteins, and amino acids are then used for bacterial protein synthesis, energy production, and in other various catabolic pathways. The resulting metabolic intermediaries and end products can then accumulate in the colorectal fluid, and their concentrations appear to depend on different parameters, including microbiota composition and metabolic activity, substrate availability, and the capacity of absorptive colonocytes to absorb these metabolites. The aim of the present review is to present how amino acid-derived bacterial metabolites can affect microbial communication between both commensal and pathogenic microorganisms, as well as their metabolism, physiology, and growth.

Mitochondrial remodeling and energy metabolism adaptations in colonic crypts during spontaneous epithelial repair after colitis induction in mice.

Mucosal healing has emerged as a therapeutic goal to achieve lasting clinical remission in ulcerative colitis. Intestinal repair in response to inflammation presumably requires higher energy supplies for the restoration of intestinal barrier and physiological functions. However, epithelial energy metabolism during intestinal mucosal healing has been little studied, whereas inflammation-induced alterations have been reported in the main energy production site, the mitochondria. The aim of the present work was to assess the involvement of mitochondrial activity and the events influencing their function during spontaneous epithelial repair after colitis induction in mouse colonic crypts. The results obtained show adaptations of colonocyte metabolism during colitis to ensure maximal ATP production for supporting energetic demand by both oxidative phosphorylation and glycolysis in a context of decreased mitochondrial biogenesis and through mitochondrial function restoration during colon epithelial repair. In parallel, colitis-induced mitochondrial ROS production in colonic epithelial cells was rapidly associated with transient expression of GSH-related enzymes. Mitochondrial respiration in colonic crypts was markedly increased during both inflammatory and recovery phases despite decreased expression of several mitochondrial respiratory chain complex subunits after colitis induction. Rapid induction of mitochondrial fusion was associated with mitochondrial function restoration. Finally, in contrast with the kinetics expression of genes involved in mitochondrial oxidative metabolism and in glycolysis, the expression of glutaminase was markedly reduced in the colonic crypts both during colitis and repair phases. Overall, our data suggest that the epithelial repair after colitis induction is characterized by a rapid and transient increased capacity for mitochondrial ATP production in a context of apparent restoration of mitochondrial biogenesis and metabolic reorientation of energy production. The potential implication of energy production adaptations within colonic crypts to sustain mucosal healing in a context of altered fuel supply is discussed.

Regulation of enteroendocrine cell respiration by the microbial metabolite hydrogen sulfide.

Endocrine functions of the gut are supported by a scattered population of cells, the enteroendocrine cells (EECs). EECs sense their environment to secrete hormones in a regulated manner. Distal EECs are in contact with various microbial compounds including hydrogen sulfide (H2S) which modulate cell respiration with potential consequences on EEC physiology. However, the effect of H2S on gut hormone secretion remains discussed and the importance of the modulation of cell metabolism on EEC functions remains to be deciphered. The aim of this project was to characterize the metabolic response of EECs to H2S and the consequences on GLP-1 secretion. We used cell line models of EECs to assess their capacity to metabolize H2S at low concentration and the associated modulation of cell respiration. We confirmed that like what is observed in colonocytes, colonic EEC model, NCI-h716 cell line rapidly metabolizes H2S at low concentrations, resulting in transient increased respiration. Higher concentrations of H2S inhibited this respiration, with the concentration threshold for inhibition depending on cell density. However, increased or inhibited oxidative respiration had little effect on acute GLP-1 secretion. Overall, we present here a first study showing the EEC capacity to detoxify low concentrations of H2S and used this model to acutely address the importance of cell respiration on secretory activity.

Intrauterine growth retardation affects liver bile acid metabolism in growing pigs: effects associated with the changes of colonic bile acid derivatives.

BACKGROUND: Intrauterine growth retardation (IUGR) is associated with severely impaired nutrient metabolism and intestinal development of pigs. Our previous study found that IUGR altered intestinal microbiota and metabolites in the colon. However, the consequences of IUGR on bile acid metabolism in pigs remained unclear. The present study aimed to investigate the bile acid metabolism in the liver and the profile of bile acid derivatives in the colon of growing pigs with IUGR using bile acid targeted metabolomics. Furthermore, we determined correlations between colonic microbiota composition and metabolites of IUGR and normal birth weight (NBW) pigs at different growth stages that were 7, 21, and 28-day-old, and the average body weight (BW) of 25, 50, and 100 kg of the NBW pigs. RESULTS: The results showed that the plasma total bile acid concentration was higher (P < 0.05) at the 25 kg BW stage and tended to increase (P = 0.08) at 28-day-old in IUGR pigs. The hepatic gene expressions related to bile acid synthesis (CYP7A1, CYP27A1, and NTCP) were up-regulated (P < 0.05), and the genes related to glucose and lipid metabolism (ATGL, HSL, and PC) were down-regulated (P < 0.05) at the 25 kg BW stage in IUGR pigs when compared with the NBW group. Targeted metabolomics analysis showed that 29 bile acids and related compounds were detected in the colon of pigs. The colonic concentrations of dehydrolithocholic acid and apocholic acid were increased (P < 0.05), while isodeoxycholic acid and 6,7-diketolithocholic acid were decreased (P < 0.05) in IUGR pigs, when compared with the NBW pigs at the 25 kg BW stage. Moreover, Spearman's correlation analysis revealed that colonic Unclassified_[Mogibacteriaceae], Lachnospira, and Slackia abundances were negatively correlated (P < 0.05) with dehydrolithocholic acid, as well as the Unclassified_Clostridiaceae abundance with 6,7-diketolithocholic acid at the 25 kg BW stage. CONCLUSIONS: These findings suggest that IUGR could affect bile acid and glucolipid metabolism in growing pigs, especially at the 25 kg BW stage, these effects being paralleled by a modification of bile acid derivatives concentrations in the colonic content. The plausible links between these modified parameters are discussed.

Probiotics or synbiotics addition to sows' diets alters colonic microbiome composition and metabolome profiles of offspring pigs.

Little information exists about the effects of maternal probiotics and synbiotics addition on the gut microbiome and metabolome of offspring. The present study evaluated the effects of probiotics or synbiotics addition to sows' diets on colonic microbiota and their metabolites in offspring using 16S rRNA gene sequencing and metabolome strategy. A total of 64 pregnant Bama mini-pigs were randomly divided into control, antibiotic, probiotics, and synbiotics groups and fed the corresponding experimental diets during pregnancy and lactation. After weaning, two piglets per litter and eight piglets per group were selected and fed a basal diet. The ß-diversity analysis showed that the colonic microbiota of offspring had a clear distinction among the four groups at 65 days of age. Maternal probiotics addition increased the Actinobacteria abundance at 65 days of age and Tenericutes and Firmicutes abundances at 95 days of age of offspring compared with the other three groups, whereas maternal antibiotic addition increased Spirochaetes and Proteobacteria abundances at 95 days of age of offspring compared with the other three groups. Metabolomic analysis showed that colonic metabolites were different between the groups, regardless of the days of age. Furthermore, both PICRUSt2 and enrichment analysis of metabolic pathways showed that maternal probiotics and synbiotics addition affected metabolism of carbohydrate, amino acid, cofactors and vitamins in the colonic microbiota. Compared with the control group, the colonic concentration of indole decreased and skatole increased in the probiotics group, whereas indole increased and skatole decreased in the synbiotics group. Maternal probiotics addition increased the colonic concentrations of acetate and butyrate at 65 and 125 days of age, whereas probiotics and synbiotics addition decreased short-chain fatty acids concentrations at 95 days of age. In addition, the colonic concentrations of putrescine, cadaverine, 1,7-heptanediamine, and spermidine were increased in the antibiotic, probiotics, and synbiotics groups compared with the control group at 95 days of age. The correlation analysis showed that Gemmiger, Roseburia, and Faecalibacterium abundances were positively correlated with acetate, propionate, and butyrate concentrations; Gemmiger, Blautia, and Faecalibacterium were positively correlated with putrescine and spermidine; and Faecalibacterium, Blautia, Clostridium, and Streptococcus were positively correlated with (R)-3-hydroxybutyric acid. Collectively, these findings suggest that probiotics and synbiotics addition to sows' diets exerts effects on offspring pigs by altering gut microbiota composition and their metabolites. The potential beneficial effect on gut health is discussed.

Lactoferrin Supplementation during Gestation and Lactation Is Efficient for Boosting Rat Pup Development.

Lactoferrin (LF) is an iron-binding protein found at relatively high concentrations in human milk. LF, which is little degraded in the infant intestinal lumen, is known to stimulate the proliferation and differentiation of the small intestine epithelial cells. The present study was designed to evaluate in the rat model the effects of bovine LF (bLF) given to the mothers during gestation and lactation on the growth of the offspring. Female Wistar rats were randomly separated into two groups of animals that received from mating and during gestation and lactation a standard diet including or not including bLF (10 g/kg of diet). The pups' growth was determined up to postnatal day 17 (PND17), and parameters related to lean and fat mass, intestinal differentiation, intestinal barrier function, bone mineral density, osteoblast activity, and brain development were measured. In addition, metabolites in pup plasma were determined at PND17. bLF was detected in the plasma and milk of the supplemented mothers as well as in the pup plasma. Although the body weight of the pups in the two groups did not differ at birth, the pups recovered from the supplemented mothers displayed an increase body weight from PND12 up to PND17. At PND17 in the bLF group, increased small intestine epithelial cell differentiation was detected, and colon barrier function was reinforced in association with increased expression of genes coding for the tight-junction proteins. Regarding bone physiology, improved bone mineral density was measured in the pups. Lastly, the plasma metabolite analysis revealed mainly higher amino acid concentrations in the LF pups as compared to the control group. Our results support that bLF ingestion by the mother during gestation and lactation can promote pup early life development. The potential interest of supplementing the mothers with bLF in the case of risk of compromised early life development of the offspring in the context of animal and human nutrition is discussed.

Fate of undigested proteins in the pig large intestine: What impact on the colon epithelium?

Apart from its obvious agronomic interest in feeding billions of people worldwide, the porcine species represents an irreplaceable experimental model for intestinal physiologists and nutritionists. In this review, we give an overview on the fate of proteins that are not fully digested in the pig small intestine, and thus are transferred into the large intestine. In the large intestine, dietary and endogenous proteins are converted to peptides and amino acids (AA) by the action of bacterial proteases and peptidases. AA, which cannot, except in the neonatal period, be absorbed to any significant level by the colonocytes, are used by the intestinal microbes for protein synthesis and for the production of numerous metabolites. Of note, the production of the AA-derived metabolites greatly depends on the amount of undigested polysaccharides in the pig's diet. The effects of these AA-derived bacterial metabolites on the pig colonic epithelium have not yet been largely studied. However, the available data, performed on colonic mucosa, isolated colonic crypts and colonocytes, indicate that some of them, like ammonia, butyrate, acetate, hydrogen sulfide (H2S), and p-cresol are active either directly or indirectly on energy metabolism in colonic epithelial cells. Further studies in that area will certainly gain from the utilization of the pig colonic organoid model, which allows for disposal of functional epithelial unities. Such studies will contribute to a better understanding of the potential causal links between diet-induced changes in the luminal concentrations of these AA-derived bacterial metabolites and effects on the colon epithelial barrier function and water/electrolyte absorption.

Production of Indole and Indole-Related Compounds by the Intestinal Microbiota and Consequences for the Host: The Good, the Bad, and the Ugly.

The intestinal microbiota metabolic activity towards the available substrates generates myriad bacterial metabolites that may accumulate in the luminal fluid. Among them, indole and indole-related compounds are produced by specific bacterial species from tryptophan. Although indole-related compounds are, first, involved in intestinal microbial community communication, these molecules are also active on the intestinal mucosa, exerting generally beneficial effects in different experimental situations. After absorption, indole is partly metabolized in the liver into the co-metabolite indoxyl sulfate. Although some anti-inflammatory actions of indole on liver cells have been shown, indoxyl sulfate is a well-known uremic toxin that aggravates chronic kidney disease, through deleterious effects on kidney cells. Indoxyl sulfate is also known to provoke endothelial dysfunction. Regarding the central nervous system, emerging research indicates that indole at excessive concentrations displays a negative impact on emotional behavior. The indole-derived co-metabolite isatin appears, in pre-clinical studies, to accumulate in the brain, modulating brain function either positively or negatively, depending on the doses used. Oxindole, a bacterial metabolite that enters the brain, has shown deleterious effects on the central nervous system in experimental studies. Lastly, recent studies performed with indoxyl sulfate report either beneficial or deleterious effects depending once again on the dose used, with missing information on the physiological concentrations that are reaching the central nervous system. Any intervention aiming at modulating indole and indole-related compound concentrations in the biological fluids should crucially take into account the dual effects of these compounds according to the host tissues considered.

Maternal Supplementation With Different Probiotic Mixture From Late Pregnancy to Day 21 Postpartum: Consequences for Litter Size, Plasma and Colostrum Parameters, and Fecal Microbiota and Metabolites in Sows.

The present study determined the effects of different probiotic mixture supplementation to sows from late pregnancy to day 21 postpartum on reproductive performance, colostrum composition, plasma biochemical parameters, and fecal microbiota and metabolites. A total of 80 pregnant sows were randomly assigned to one of four groups (20 sows per group). The sows in the control group (CON group) were fed a basal diet, and those in the BS-A+B, BS-A+BL, and BS-B+BL groups were fed basal diets supplemented with 250 g/t of different probiotic mixture containing either 125 g/t of Bacillus subtilis A (BS-A), Bacillus subtilis B (BS-B), and/or Bacillus licheniformis (BL), respectively. The trial period was from day 85 of pregnancy to day 21 postpartum. The results showed that different dietary probiotic mixture supplementation increased (P < 0.05) the average weaning weight and average daily gain of piglets, while dietary BS-A+BL supplementation increased the number of weaned piglets (P < 0.05), litter weight (P = 0.06), litter weight gain (P = 0.06), and litter daily gain (P = 0.06) at weaning compared with the CON group. Different dietary probiotic mixture supplementation improved (P < 0.05) the colostrum quality by increasing the fat and dry matter concentrations, as well as the protein and urea nitrogen concentrations in the BS-A+BL group. Dietary probiotic mixture BS-B+BL increased the plasma total protein on days 1 and 21 postpartum while decreased the plasma albumin on day 1 postpartum (P < 0.05). In addition, the plasma high-density lipoprotein-cholesterol was increased in the BS-A+B and BS-B+BL groups on day 21 postpartum, while plasma ammonia was decreased in the BS-A+B and BS-A+BL groups on day 1 and in the three probiotic mixtures groups on day 21 postpartum (P < 0.05). Dietary supplementation with different probiotic mixture also modified the fecal microbiota composition and metabolic activity in sows during pregnancy and postpartum stages. Collectively, these findings suggest that maternal supplementation with Bacillus subtilis in combination with Bacillus licheniformis are promising strategies for improving the reproductive performance and the overall health indicators in sows, as well as the growth of their offspring.

Dual effects of the tryptophan-derived bacterial metabolite indole on colonic epithelial cell metabolism and physiology: comparison with its co-metabolite indoxyl sulfate.

Indole, which is produced by the intestinal microbiota from L-tryptophan, is recovered at millimolar concentrations in the human feces. Indoxyl sulfate (IS), the main indole co-metabolite, can be synthesized by the host tissues. Although indole has been shown to restore intestinal barrier function in experimental colitis, little is known on the effects of indole and IS on colonic epithelial cell metabolism and physiology. In this study, we compared the effects of indole and IS on the human colonic epithelial HT-29 Glc-/+ and Caco-2 cell lines, exposed to these compounds for 1-48 h. Indole, but not IS, was cytotoxic at 5 mM, altering markedly colonocyte proliferation. Both molecules, used up to 2.5 mM, induced a transient oxidative stress in colonocytes, that was detected after 1 h, but not after 48 h exposure. This was associated with the induction after 24 h of the expression of glutathione reductase, heme oxygenase, and cytochrome P450 (CYP)1B1. Indole and IS used at 2.5 mM impaired colonocyte respiration by diminishing mitochondrial oxygen consumption and maximal respiratory capacity. Indole, but not IS, displayed a slight genotoxic effect on colonocytes. Indole, but not IS, increased transepithelial resistance in colonocyte monolayers. Indole and IS used at 2.5 mM, induced a secretion of the pro-inflammatory interleukin-8 after 3 h incubation, and an increase of tumor necrosis factor-α secretion after 48 h. Although our results suggest beneficial effect of indole on epithelial integrity, overall they indicate that indole and IS share adverse effects on colonocyte respiration and production of reactive oxygen species, in association with the induction of enzymes of the antioxidant defense system. This latter process can be viewed as an adaptive response toward oxidative stress. Both compounds increased the production of inflammatory cytokines from colonocytes. However, only indole, but not IS, affected DNA integrity in colonocytes. Since colonocytes little convert indole to IS, the deleterious effects of indole on colonocytes appear to be unrelated to its conversion to IS.

Tolerable amounts of amino acids for human supplementation: summary and lessons from published peer-reviewed studies.

Amino acid supplementation may be indicated to correct for insufficient amino acid intake in healthy individuals, and in specific physiological or pathophysiological situations. However, there is a concern to not supplement beyond the tolerable upper intake level (UL) by determining parameters of no-observed-adverse-effect level (NOAEL) or lowest-observed-adverse-effect level (LOAEL) for each amino acid. Since the NOAEL and LOAEL values are at least one order of magnitude different when comparing the values obtained in rats and humans, the aim of this review is to evaluate to what extent the amino acid UL measured in the rat model, when referenced to the dietary usual consumption (UC) and dietary requirement (RQ) for indispensable amino acids, may be used as an approximation of the UL in humans. This review then compares the ratios of the NOAEL or LOAEL over UC and RQ in the rat model with the same ratios calculated in humans for the nine amino acids (arginine, serine, glycine, histidine, leucine, lysine, methionine, phenylalanine, and tryptophan) for which this comparison can be done. From the calculations made, it appears that for these 9 amino acids, the calculated ratios for rats and humans, although rather different for several amino acids, remains for all of them in the same order of magnitude. For tryptophan, tyrosine, and valine, the ratios calculated in rats are markedly different according to the sex of animals, raising the view that it may be also the case in humans.

Dietary Supplementation With Xylo-oligosaccharides Modifies the Intestinal Epithelial Morphology, Barrier Function and the Fecal Microbiota Composition and Activity in Weaned Piglets.

The present study determined the effects of dietary xylo-oligosaccharides (XOS) supplementation on the morphology of jejunum and ileum epithelium, fecal microbiota composition, metabolic activity, and expression of genes related to colon barrier function. A total of 150 piglets were randomly assigned to one of five groups: a blank control group (receiving a basal diet), three XOS groups (receiving the basal diet supplemented with 100, 250, and 500 g/t XOS, respectively), as well as a positive control group, used as a matter of comparison, that received the basal diet supplemented with 0.04 kg/t virginiamycin, 0.2 kg/t colistin, and 3,000 mg/kg ZnO. The trial was carried out for 56 days. The results showed that the lowest dose tested (100 g/t XOS) increased (P < 0.05) the ileal villus height, the relative amount of Lactobacillus and Bifidobacterium spp., and the concentration of acetic acid and short-chain fatty acid in feces when compared with the blank control group. In conclusion, dietary 100 g/t XOS supplementation modifies the intestinal ecosystem in weaned piglets in an apparently overall beneficial way.

Dynamic Changes of Metabolite Profiles in Maternal Biofluids During Gestation Period in Huanjiang Mini-Pigs.

The biochemical parameters related to nitrogenous metabolism in maternal biofluids may be linked and even reflect the fetal metabolism and growth. The present study have measured the concentrations of various parameters related to amino acid (AA) and lipid metabolism, as well as different metabolites including the free AAs in maternal plasma and amniotic and allantoic fluid corresponding to fetuses with different body weight (BW) during different gestation periods, in order to identify the possible relationships between biochemical parameters and fetal growth. A total of 24 primiparous Huanjiang mini-pigs were fed with a standard diet. Data showed that, from day 45 to day 110 of gestation, the maternal plasma levels of alanine aminotransferase (ALT), albumin (ALB), Ile, Orn, Car, α-ABA, and ß-AiBA increased (P < 0.05); while the levels of ammonia (AMM), choline esterase (CHE), high density lipoprotein-cholesterol (HDL-C), Leu, Glu, Cys, Asp, and Hypro decreased (P < 0.05). From day 45 to 110 of gestation, the amniotic fluid levels of aspartate transaminase (AST), CHE, total protein (TP), and urea nitrogen (UN) increased (P < 0.05), as well as the level of CHE and TP and concentration of Pro in allantoic fluid; while the amniotic fluid concentrations of Arg, Glu, Orn, Pro, and Tau decreased (P < 0.05), as well as allantoic fluid concentrations of Arg and Glu. At day 45 of gestation, the amniotic fluid concentrations of Arg, Orn, and Tau corresponding to the highest BW (HBW) fetuses were higher (P < 0.05), whereas the allantoic fluid concentrations of His and Pro were lower (P < 0.05) when compared with the lowest BW (LBW) fetuses. At day 110 of gestation, the amniotic fluid concentration of Tau corresponding to the HBW fetuses was higher (P < 0.05) than the LBW fetuses. These findings show that the sows display increased protein utilization and decreased lipid metabolism and deposition from day 75 to 110 of gestation. In addition, our data are indicative of a likely stronger ability of HBW fetuses to metabolize protein; and finally of a possible key role of Arg, Gln, Glu, Pro, Tau, and His for the fetal growth and development.

Short-chain fatty acids and bile acids in human faeces are associated with the intestinal cholesterol conversion status.

BACKGROUND AND PURPOSE: The analysis of human faecal metabolites can provide an insight into metabolic interactions between gut microbiota and the host organism. The creation of metabolic profiles in faeces has received little attention until now, and reference values, especially in the context of dietary and therapeutic interventions, are missing. Exposure to xenobiotics significantly affects the physiology of the microbiome, and microbiota manipulation and short-chain fatty acid administration have been proposed as treatment targets for several diseases. The aim of the present study is to give concomitant concentration ranges of faecal sterol species, bile acids and short-chain fatty acids, based on a large cohort. EXPERIMENTAL APPROACH: Sterol species, bile acids and short-chain fatty acids in human faeces from 165 study participants were quantified by LC-MS/MS. For standardization, we refer all values to dry weight of faeces. Based on the individual intestinal sterol conversion, we classified participants into low and high converters according to their coprostanol/cholesterol ratio. KEY RESULTS: Low converters excrete more straight-chain fatty acids and bile acids than high converters; 5th and 95th percentile and median of bile acids and short-chain fatty acids were calculated for both groups. CONCLUSION AND IMPLICATIONS: We give concentration ranges for 16 faecal metabolites that can serve as reference values. Patient stratification into high or low sterol converter groups is associated with significant differences in faecal metabolites with biological activities. Such stratification should then allow better assessment of faecal metabolites before therapeutic interventions. LINKED ARTICLES: This article is part of a themed issue on Oxysterols, Lifelong Health and Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.16/issuetoc.