A distinct clade of Bifidobacterium longum in the gut of Bangladeshi children thrives during weaning.

The gut microbiome has an important role in infant health and development. We characterized the fecal microbiome and metabolome of 222 young children in Dhaka, Bangladesh during the first two years of life. A distinct Bifidobacterium longum clade expanded with introduction of solid foods and harbored enzymes for utilizing both breast milk and solid food substrates. The clade was highly prevalent in Bangladesh, present globally (at lower prevalence), and correlated with many other gut taxa and metabolites, indicating an important role in gut ecology. We also found that the B. longum clades and associated metabolites were implicated in childhood diarrhea and early growth, including positive associations between growth measures and B. longum subsp. infantis, indolelactate and N-acetylglutamate. Our data demonstrate geographic, cultural, seasonal, and ecological heterogeneity that should be accounted for when identifying microbiome factors implicated in and potentially benefiting infant development.

Dedicated macrophages organize and maintain the enteric nervous system.

Correct development and maturation of the enteric nervous system (ENS) is critical for survival1. At birth, the ENS is immature and requires considerable refinement to exert its functions in adulthood2. Here we demonstrate that resident macrophages of the muscularis externa (MMϕ) refine the ENS early in life by pruning synapses and phagocytosing enteric neurons. Depletion of MMϕ before weaning disrupts this process and results in abnormal intestinal transit. After weaning, MMϕ continue to interact closely with the ENS and acquire a neurosupportive phenotype. The latter is instructed by transforming growth factor-ß produced by the ENS; depletion of the ENS and disruption of transforming growth factor-ß signalling result in a decrease in neuron-associated MMϕ associated with loss of enteric neurons and altered intestinal transit. These findings introduce a new reciprocal cell-cell communication responsible for maintenance of the ENS and indicate that the ENS, similarly to the brain, is shaped and maintained by a dedicated population of resident macrophages that adapts its phenotype and transcriptome to the timely needs of the ENS niche.

The Timed Pathway to Homeostasis.

Al Nabhani et al. (2019) describe the weaning reaction, a transient, microbiota-induced innate immune stimulation during the third and fourth weeks after birth that is associated with protection from immune-mediated enteric diseases in adulthood. This strictly timed, non-redundant process highlights the cooperative action of dietary, microbial, and developmental factors in the establishment of immune homeostasis.

A Weaning Reaction to Microbiota Is Required for Resistance to Immunopathologies in the Adult.

Microbes colonize all body surfaces at birth and participate in the development of the immune system. In newborn mammals, the intestinal microbiota is first shaped by the dietary and immunological components of milk and then changes upon the introduction of solid food during weaning. Here, we explored the reactivity of the mouse intestinal immune system during the first weeks after birth and into adulthood. At weaning, the intestinal microbiota induced a vigorous immune response-a "weaning reaction"-that was programmed in time. Inhibition of the weaning reaction led to pathological imprinting and increased susceptibility to colitis, allergic inflammation, and cancer later in life. Prevention of this pathological imprinting was associated with the generation of RORγt+ regulatory T cells, which required bacterial and dietary metabolites-short-chain fatty acids and retinoic acid. Thus, the weaning reaction to microbiota is required for immune ontogeny, the perturbation of which leads to increased susceptibility to immunopathologies later in life.

The origin of placental mammal life histories.

After the end-Cretaceous extinction, placental mammals quickly diversified1, occupied key ecological niches2,3 and increased in size4,5, but this last was not true of other therians6. The uniquely extended gestation of placental young7 may have factored into their success and size increase8, but reproduction style in early placentals remains unknown. Here we present the earliest record of a placental life history using palaeohistology and geochemistry, in a 62 million-year-old pantodont, the clade including the first mammals to achieve truly large body sizes. We extend the application of dental trace element mapping9,10 by 60 million years, identifying chemical markers of birth and weaning, and calibrate these to a daily record of growth in the dentition. A long gestation (approximately 7 months), rapid dental development and short suckling interval (approximately 30-75 days) show that Pantolambda bathmodon was highly precocial, unlike non-placental mammals and known Mesozoic precursors. These results demonstrate that P. bathmodon reproduced like a placental and lived at a fast pace for its body size. Assuming that P. bathmodon reflects close placental relatives, our findings suggest that the ability to produce well-developed, precocial young was established early in placental evolution, and that larger neonate sizes were a possible mechanism for rapid size increase in early placentals.

Going Full TeRM: The Seminal Role of Tissue-Resident Macrophages in Organ Remodeling during Pregnancy and Lactation.

During pregnancy and lactation, the uterus and mammary glands undergo remarkable structural changes to perform their critical reproductive functions before reverting to their original dormant state upon childbirth and weaning, respectively. Underlying this incredible plasticity are complex remodeling processes that rely on coordinated decisions at both the cellular and tissue-subunit levels. With their exceptional versatility, tissue-resident macrophages play a variety of supporting roles in these organs during each stage of development, ranging from maintaining immune homeostasis to facilitating tissue remodeling, although much remains to be discovered about the identity and regulation of individual macrophage subsets. In this study, we review the increasingly appreciated contributions of these immune cells to the reproductive process and speculate on future lines of inquiry. Deepening our understanding of their interactions with the parenchymal or stromal populations in their respective niches may reveal new strategies to ameliorate complications in pregnancy and breastfeeding, thereby improving maternal health and well-being.

Maternal Obesogenic Diet Attenuates Microbiome-Dependent Offspring Weaning Reaction with Worsening of Steatotic Liver Disease.

The mechanisms by which maternal obesity increases the susceptibility to steatotic liver disease in offspring are incompletely understood. Models using different maternal obesogenic diets (MODEs) display phenotypic variability, likely reflecting the influence of timing and diet composition. This study compared three maternal obesogenic diets using standardized exposure times to identify differences in offspring disease progression. This study found that the severity of hepatic inflammation and fibrosis in the offspring depends on the composition of the maternal obesogenic diet. Offspring cecal microbiome composition was shifted in all MODE groups relative to control. Decreased α-diversity in some MODE offspring with shifts in abundance of multiple genera were suggestive of delayed maturation of the microbiome. The weaning reaction typically characterized by a spike in intestinal expression of Tnfa and Ifng was attenuated in MODE offspring in an early microbiome-dependent manner using cross-fostering. Cross-fostering also switched the severity of disease progression in offspring dependent on the diet of the fostering dam. These results identify maternal diet composition and timing of exposure as modifiers in mediating transmissible changes in the microbiome. These changes in the early microbiome alter a critical window during weaning that drives susceptibility to progressive liver disease in the offspring.

Peri-weaning cholera toxin consumption suppresses chemically-induced carcinogenesis in mice.

Gastrointestinal bacteria are known to have an impact on local and systemic immunity, and consequently either promote or suppress cancer development. Following the notion that perinatal bacterial exposure might confer immune system competency for life, we investigated whether early-life administration of cholera-toxin (CT), a protein exotoxin of the small intestine pathogenic bacterium Vibrio cholerae, may shape local and systemic immunity to impart a protective effect against tumor development in epithelia distantly located from the gut. For that, newborn mice were orally treated with low non-pathogenic doses of CT and later challenged with the carcinogen 7,12-dimethylbenzanthracene (DMBA), known to cause mainly mammary, but also skin, lung and stomach cancer. Our results revealed that CT suppressed the overall incidence and multiplicity of tumors, with varying efficiencies among cancer types, and promoted survival. Harvesting mouse tissues at an earlier time-point (105 instead of 294 days), showed that CT does not prevent preneoplastic lesions per se but it rather hinders their evolution into tumors. CT pretreatment universally increased apoptosis in the cancer-prone mammary, lung and nonglandular stomach, and altered the expression of several cancer-related molecules. Moreover, CT had a long-term effect on immune system cells and factors, the most prominent being the systemic neutrophil decrease. Finally, CT treatment significantly affected gut bacterial flora composition, leading among others to a major shift from Clostridia to Bacilli class abundance. Overall, these results support the notion that early-life CT consumption is able to affect host's immune, microbiome and gene expression profiles toward the prevention of cancer.

Progression of swine fecal microbiota during early stages of life and its association with performance: a longitudinal study.

BACKGROUND: It is vital to understand healthy gut microbiota composition throughout early life stages when environments are changing, and immunity is developing. There are limited large-scale longitudinal studies classifying healthy succession of swine microbiota. The objectives of this study were to (a) determine the microbiota composition of fecal samples collected from piglets within a few days after birth until one-week post-weaning, and (b) investigate the associations of early fecal microbiota with pig growth performance in nursery and later growing stages. Fecal samples were collected from nine cohorts of 40 pigs (n = 360) from distinct farrowing sources in Ontario and Quebec, Canada at four timepoints from birth to one-week post-weaning, with pig body weight was recorded at each fecal sampling. RESULTS: Microbiota was dominated by the phyla Firmicutes, Bacteroides and Proteobacteria. There were notable differences in genera abundance between pigs from different provinces and farming systems. Over the early life stage, the genera Bacteroides, Escherichia/Shigella, and Clostridium cluster XIVa were abundant preweaning, while Prevotella dominated post-weaning. Hierarchical clustering identified three major stages of microbiota development, each associated with distinct composition. Stage one occurs from birth to 7 days, stage two from 7 days after birth until weaning, and stage three from weaning to one-week post-weaning. Three enterotypes were identified in stage two that showed differences in growth before weaning, and in the grower production stage. Piglets with a microbiota enterotype characterized by higher abundance of Prevotella and unclassified Ruminococcaceae had lower growth performance in the pre-weaning stage, and the growing stage. CONCLUSION: These findings help identify the timing of microbiota shifts across early swine life which may be the optimal time for external intervention to shift the microbiota to a beneficial state. The project findings should help decrease antimicrobial use, increase animal welfare, and have positive economic impacts.

Microbe-derived Antioxidants Enhance Lipid Synthesis by Regulating the Hepatic AMPKα-SREBP1c Pathway in Weanling Piglets.

BACKGROUND: Weaning usually causes low feed intake and weight loss in piglets, which mobilizes lipid to energize. The microbe-derived antioxidants (MAs) exhibit great potential in antioxidation, anti-inflammation, and metabolic regulation. OBJECTIVES: We aimed to investigate the changes of lipid metabolism postweaning and effects of MA on growth performance and hepatic lipid metabolism in weanling piglets. METHODS: In the first experiment, piglets weaned at 21 d of age were slaughtered on weaning day (d0), 4 (d4), and 14 (d14) postweaning (6 piglets per day). In the second experiment, piglets were divided into 2 groups, receiving MA (MA) and saline gavage (CON), respectively. All piglets were weaned at 21 d of age and 6 piglets from each group were slaughtered at 25 d of age. RESULTS: In experiment 1, the serum triglyceride, total cholesterol (TC), and LDL cholesterol on d4 and d14 declined significantly compared with d0 (P < 0.05). The serum leptin on d0 was higher than that on d4 and d14 (P < 0.05). The serum ghrelin kept increasing from d0 to d14 (P < 0.05). The hepatic hormone-sensitive lipase and adipose triglyceride lipase first increased from d0 to d4 and then decreased from d4 to d14 (P < 0.05). In experiment 2, the average daily gain and average daily feed intake from 21 to 25 d of age increased in the MA group compared with the CON group (P < 0.05). The serum TC, hepatic TC, and glucose of MA group showed a significant increase than that of the CON group (P < 0.05). The expression of SCD1, ACAT2, and PPARγ were upregulated in the MA group (P < 0.05). Contrary to the decreased expression of phosphorylation of adenosine 5'-monophosphate-activated protein kinase alfa subunit (Thr172), the nuclear sterol regulatory element-binding protein 1c, fatty acid synthase, and peroxisome proliferator-activated receptor gamma of MA group increased than that of CON group (P < 0.05). CONCLUSIONS: Weaning promoted hepatic lipolysis and MA could enhance lipid synthesis by regulating adenosine 5'-monophosphate-activated protein kinase alfa subunit-sterol regulatory element-binding protein 1c pathway, thus improving growth performance of weanling piglets.

Prepuberty is a window period for curcumin to prevent obesity in postnatal overfed rats.

BACKGROUND: Overnutrition in early life increases the risk of obesity and metabolic diseases. We investigated the effects and the window period of a curcumin (CUR) diet on postnatal overfed rats. METHODS: Male rats aged 3 days were randomly divided into normal litters (NL, 10 pups/litter) and small litters (SL, 3 pups/litter). After weaning (Week 3, W3), NL rats were fed a normal diet (NL) and SL rats were fed a normal diet (SL) or 2% CUR diet from weaning (W3) (SL-CURW13), beginning of puberty (W6) (SL-CURW16), or end of puberty (W8) (SL-CURW18) for 10 weeks. RESULTS: Body weight, glucose intolerance and hyperlipidemia in the SL rats were higher than in the NL rats, especially after puberty. After the CUR intervention, SL-CURW13 and SL-CURW16 rats showed lower body weight gain, adipose tissue weight and mRNA level of C/EBPα in SAT, along with higher mRNA levels of ß-catenin. There was no difference between SL and SL-CURW18 rats. Glucose tolerance, serum lipids and hepatic lipids recovered to normal in the SL-CURW13 rats, but only partially in the SL-CURW16 and SL-CURW18 rats. CONCLUSION: Prepuberty is a window period for CUR intervention to improve programmed outcomes in postnatal overfed rats. IMPACT: Overnutrition during the first 1000 days of life has persistent negative effects on metabolism. Strategies should be taken to prevent overnutrition in early life to reduce the risk of obesity and metabolic disease in later life. A small-litter rat model was utilized to simulate early-life overnutrition in humans. We investigated the different effects and critical period for curcumin intervention on postnatal overfed rats. Dietary curcumin intervention before puberty could effectively transform nutritional programming to reduce obesity and metabolic disorders caused by early-life overnutrition, and an earlier intervention might predict a better outcome.

Optimal positive-end expiratory pressure weaning in acute respiratory distress syndrome patients.

PURPOSE OF REVIEW: Positive-end expiratory pressure (PEEP) is a tool in managing acute respiratory distress syndrome (ARDS). In this review, we discuss the various approaches to weaning PEEP after the acute phase of ARDS. RECENT FINDINGS: There is a paucity of research specifically looking at the differences between PEEP weaning protocols. Data in some populations though, particularly those with elevated BMI, suggest that a physiologic approach to PEEP weaning may be helpful. Use of various tools to optimize PEEP prior to and during spontaneous breathing trials (SBTs) may allow for improved alveolar recruitment and respiratory outcomes. SUMMARY: Although further prospective studies are warranted, we should consider using a physiologic approach to PEEP weaning in ARDS rather than a one size fits all model, which is currently the standard used in many clinical trials and throughout many ICUs.

Diet and deprivation in pregnancy: a rat model to investigate the effects of the maternal diet on the growth of the dam and its offspring.

The offspring of women in the poorest socio-economic groups in Western societies have an increased risk of developing non-communicable disease in adult life. Deprivation is closely related to the consumption of a diet with an excess of energy (sugar and fat), salt and a shortage of key vitamins. To test the hypothesis that this diet adversely affects the development and long-term health of the offspring, we have formulated two rodent diets, one with a nutrient profile corresponding to the diet of pregnant women in the poorest socio-economic group (DEP) and a second that incorporated current UK recommendations for the diet in pregnancy (REC). Female rats were fed the experimental diets for the duration of gestation and lactation and the offspring compared with those from a reference group fed the AIN-93G diet. The growth trajectory of DEP and REC offspring was reduced compared with the AIN-93G. The REC offspring diet had a transient increase in adipose reserves at weaning, but by 30 weeks of age the body composition of all three groups was similar. The maternal diet had no effect on the homoeostatic model assessment index or the insulin tolerance of the offspring. Changes in hepatic gene expression in the adult REC offspring were consistent with an increased hepatic utilisation of fatty acids and a reduction in de novo lipogenesis. These results show that despite changes in growth and adiposity maternal metabolic adaptation minimises the adverse consequences of the imbalanced maternal diet on the metabolism of the offspring.

Effect of different doses of camelina cake inclusion as a substitute of dietary soyabean meal on growth performance and gut health of weaned pigs.

Camelina cake (CAM) is a co-product proposed as an alternative protein source; however, piglet data are still limited. This study aimed to evaluate the effect of different doses of CAM in substitution of soyabean meal on the growth, health and gut health of weaned pigs. At 14 d post-weaning (d0), sixty-four piglets were assigned either to a standard diet or to a diet with 4 %, 8 % or 12 % of CAM. Piglets were weighed weekly. At d7 and d28, faeces were collected for microbiota and polyamine and blood for reactive oxygen metabolites (ROM) and thyroxine analysis. At d28, pigs were slaughtered, organs were weighed, pH was recorded on gut, colon was analysed for volatile fatty acids (VFA) and jejunum was used for morphological and gene expression analysis. Data analysis was carried out using a mixed model including diet, pen and litter as factors; linear and quadratic contrasts were tested. CAM linearly reduced the average daily gain from d0-d7, d0-d14, d0-d21 and d0-d28 (P ≤ 0·01). From d0-d7 increasing CAM linearly decreased feed intake (P = 0·04) and increased linearly the feed to gain (P = 0·004). CAM increased linearly the liver weight (P < 0·0001) and affected the cadaverine (P < 0·001). The diet did not affect the ROM, thyroxine, intestinal pH, VFA and morphology. All doses of CAM increased the α diversity indices at d28 (P < 0·05). CAM at 4 % promoted the abundance of Butyricicoccaceae_UCG-008. Feeding with CAM enhanced resilience in the gut microbiome and can be evaluated as a potential alternative protein source with dose-dependent limitations on piglet growth performance.

Innate and adaptive lymphocytes sequentially shape the gut microbiota and lipid metabolism.

The mammalian gut is colonized by numerous microorganisms collectively termed the microbiota, which have a mutually beneficial relationship with their host. Normally, the gut microbiota matures during ontogeny to a state of balanced commensalism marked by the absence of adverse inflammation. Subsets of innate lymphoid cells (ILCs) and conventional T cells are considered to have redundant functions in containment and clearance of microbial pathogens, but how these two major lymphoid-cell populations each contribute to shaping the mature commensal microbiome and help to maintain tissue homeostasis has not been determined. Here we identify, using advanced multiplex quantitative imaging methods, an extensive and persistent phosphorylated-STAT3 signature in group 3 ILCs and intestinal epithelial cells that is induced by interleukin (IL)-23 and IL-22 in mice that lack CD4+ T cells. By contrast, in immune-competent mice, phosphorylated-STAT3 activation is induced only transiently by microbial colonization at weaning. This early signature is extinguished as CD4+ T cell immunity develops in response to the expanding commensal burden. Physiologically, the persistent IL-22 production from group 3 ILCs that occurs in the absence of adaptive CD4+ T-cell activity results in impaired host lipid metabolism by decreasing lipid transporter expression in the small bowel. These findings provide new insights into how innate and adaptive lymphocytes operate sequentially and in distinct ways during normal development to establish steady-state commensalism and tissue metabolic homeostasis.

The cotton swab method: an accurate and less invasive way to assess fecal consistency in weaned pigs.

BACKGROUND: Researchers and pig veterinarians are interested in assessing pigs' fecal consistency. This study developed a standardized protocol and scale for the cotton swab method, which is a way of assessing the fecal consistency in pigs. The accuracy of the cotton swab method was evaluated in weaned pigs using fecal dry-matter analysis as a golden standard. The study also proposed fecal dry-matter percentage thresholds for the categorization of fecal consistency on a four-point scale. RESULTS: The thresholds of 10.3%, 16.6%, and 21.9% fecal dry-matter were suggested for categorization of the consistency of fecal samples on a four-point scale. The accuracy of the cotton swab method was high. The agreement to the four-point fecal consistency score derived from the fecal dry-matter percentage was almost perfect (weighted Gwet's agreement coefficient = 0.87 [95% confidence interval: 0.84; 0.91]). The cotton swab method had a sensitivity of 85.0% (95% confidence interval: 76.5; 91.4) and a specificity of 95.2% (95% confidence interval: 92.0; 97.3) when used to diagnose whether pigs had diarrhea or not. For non-diarrheic pigs, the method almost always (n = 287/289) required less handling than the collection of a fecal sample by digital rectal manipulation. CONCLUSION: The cotton swab method is an accurate way to assess fecal consistency in pigs, both on a four-point scale and as a dichotomous diarrhea score. The method is quick to perform and less invasive than methods relying on the collection of fecal samples. New fecal dry-matter thresholds between feces of different consistencies were proposed.

Exploring the effects of Hippo signaling pathway on rumen epithelial proliferation.

BACKGROUND: The current understanding to the mechanism of rumen development is limited. We hypothesized that the Hippo signaling pathway controlled the proliferation of rumen epithelium (RE) during postnatal development. In the present study, we firstly tested the changes of the Hippo signaling pathway in the RE during an early growing period from d5 to d25, and then we expanded the time range to the whole preweaning period (d10-38) and one week post weaning (d45). An in vitro experiment was also carried out to verify the function of Hippo signaling pathway during RE cell proliferation. RESULTS: In the RE of lambs from d5 to d25, the expression of baculoviral IAP repeat containing (BIRC3/5) was increased, while the expressions of large tumor suppressor kinase 2 (LATS2), TEA domain transcription factor 3 (TEAD3), axin 1 (AXIN1), and MYC proto-oncogene (MYC) were decreased with rumen growth. From d10 to d38, the RE expressions of BIRC3/5 were increased, while the expressions of LATS2 and MYC were decreased, which were similar with the changes in RE from d5 to d25. From d38 to d45, different changes were observed, with the expressions of LATS1/2, MOB kinase activator 1B (MOB1B), and TEAD1 increased, while the expressions of MST1 and BIRC5 decreased. Correlation analysis showed that during the preweaning period, the RE expressions of BIRC3/5 were positively correlated with rumen development variables, while LAST2 was negatively correlated with rumen development variables. The in vitro experiment validated the changes of LATS2 and BIRC3/5 in the proliferating RE cells, which supported their roles in RE proliferation during preweaning period. CONCLUSIONS: Our results suggest that the LATS2-YAP1-BIRC3/5 axis participates in the RE cell proliferation and promotes rumen growth during the preweaning period.

Molecular characterization of Escherichia coli virulence markers in neonatal and postweaning piglets from major pig-producing districts of Uganda.

BACKGROUND: Piggery production is highly constrained by diseases, with diarrhoea in piglets being a major cause of economic losses to smallholder farmers in Uganda. Enterotoxigenic Escherichia coli (ETEC) is thought to be one of the major etiologies of this diarrhoea. A cross-sectional study was carried out in two high pig-producing districts of Uganda with the aim of determining the significance of piglet diarrhoea and the pathogenic determinants of causative E. coli. METHODOLOGY: A total of 40 households with piglets were visited in each district for a questionnaire survey and faecal sample collection. The questionnaire-based data collected included; demographic data and pig management practices. E. coli were isolated from diarrheic (43) and non-diarrheic (172) piglets and were subjected to antimicrobial susceptibility testing against nine commonly used antimicrobial agents. The E. coli isolates were further screened for the presence of 11 enterotoxin and fimbrial virulence gene markers using multiplex polymerase chain reaction. Data entry, cleaning, verification and descriptive statistics were performed using Microsoft Excel. Statistical analysis to determine any association between the presence of virulence markers and diarrhea in piglets was done using SPSS software (Version 23), with a p value of less than 0.05 taken as a statistically significant association. RESULTS: Escherichia coli were recovered from 81.4% (175/215) of the faecal samples. All the isolates were resistant to erythromycin, and most showed high resistance to tetracycline (71%), ampicillin (49%), and trimethoprim sulfamethoxazole (45%). More than half of the isolates (58.3%) carried at least one of the 11 virulence gene markers tested. EAST1 was the most prevalent virulence marker detected (35.4%), followed by STb (14.8%). Expression of more than one virulence gene marker was observed in 6.2% of the isolates, with the EAST1/STa combination being the most prevalent. Three adhesins; F17 (0.6%), F18 (6.3%) and AIDA-I (0.6%) were detected, with F18 being the most encountered. There was a statistically significant association between the occurrence of piglet diarrhoea and the presence of the AIDA-1 (p value = 0.037) or EAST1 (p value = 0.011) gene marker among the isolates. CONCLUSION AND RECOMMENDATION: The level of antimicrobial resistance among E. coli isolates expressing virulence markers were high in the sampled districts. The study established a significant association between presence of EAST1 and AIDA-I virulence markers and piglet diarrhea. Further studies should be carried out to elucidate the main adhesins borne by these organisms in Uganda and the actual role played by EAST1 in the pathogenesis of the infection since most isolates expressed this gene.

Weaning and depression: a closer look.

The association of weaning with depression has long been recognized. However, interest in the study of post-weaning depression has waned over the last few decades partly due to changes in the nosology of perinatal psychiatric disorders. In this paper, we review the relevant literature and conclude that post-weaning depression is a rare but severe complication of breastfeeding cessation. Given that post-weaning depression is an understudied and often undiagnosed clinical condition, research is needed to address this important unmet need.

Towards identification of new genetic determinants for post-weaning diarrhea in piglets.

Post-weaning diarrhea in pigs is a considerable challenge in the pig farming industry due to its effect on animal welfare and production costs, as well as the large volume of antibiotics, which are used to treat diarrhea in pigs after weaning. Previous studies have revealed loci on SSC6 and SSC13 associated with susceptibility to specific diarrhea causing pathogens. This study aimed to identify new genetic loci for resistance to diarrhea based on phenotypic data. In depth clinical characterization of diarrhea was performed in 257 pigs belonging to two herds during the first 14 days post weaning. The daily diarrhea assessments were used for the classification of pigs into case and control groups. Pigs were assigned to case and control groups based only on the incidence of diarrhea in the second week of the study in order to differentiate between differences in etiology. Genome-wide association studies and metabolomics association analysis were performed in order to identify new biological determinants for diarrhea susceptibility. With the present work, we revealed a new locus for diarrhea resistance on SSC16. Furthermore, studies of metabolomics in the same pigs revealed one metabolite associated with diarrhea.