Critical to the design and assessment of interventions for enteropathy and its developmental consequences in children living in impoverished conditions are non-invasive biomarkers that can detect intestinal damage and predict its effects on growth and development. We therefore assessed fecal, urinary and systemic biomarkers of enteropathy and growth predictors in 375 6–26 month-old children with varying degrees of malnutrition (stunting or wasting) in Northeast Brazil. 301 of these children returned for followup anthropometry after 2-6m. Biomarkers that correlated with stunting included plasma IgA anti-LPS and anti-FliC, zonulin (if >12m old), and intestinal FABP (I-FABP, suggesting prior barrier disruption); and with citrulline, tryptophan and with lower serum amyloid A (SAA) (suggesting impaired defenses). In contrast, subsequent growth was predicted in those with higher fecal MPO or A1AT and also by higher L/M, plasma LPS, I-FABP and SAA (showing intestinal barrier disruption and inflammation). Better growth was predicted in girls with higher plasma citrulline and in boys with higher plasma tryptophan. Interactions were also seen with fecal MPO and neopterin in predicting subsequent growth impairment.Biomarkers clustered into markers of 1) functional intestinal barrier disruption and translocation, 2) structural intestinal barrier disruption and inflammation and 3) systemic inflammation. Principle components pathway analyses also showed that L/M with %L, I-FABP and MPO associate with impaired growth, while also (like MPO) associating with a systemic inflammation cluster of kynurenine, LBP, sCD14, SAA and K/T. Systemic evidence of LPS translocation associated with stunting, while markers of barrier disruption or repair (A1AT and Reg1 with low zonulin) associated with fecal MPO and neopterin.We conclude that key noninvasive biomarkers of intestinal barrier disruption, LPS translocation and of intestinal and systemic inflammation can help elucidate how we recognize, understand, and assess effective interventions for enteropathy and its growth and developmental consequences in children in impoverished settings.

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Prototheca zopfii is an alga increasingly isolated from bovine mastitis. of the two genotypes of P. zopfii (genotype i and ii (Gt-i and-ii)), P. zopfii Gt-ii is the genotype associated with acute mastitis and decreased milk production, although its pathogenesis is not well known. the objective was to determine inflammatory and apoptotic roles of P. zopfii Gt-ii in cultured mammary epithelial cells (from cattle and mice) and murine macrophages and using a murine model of mastitis. Prototheca zopfii Gt-ii (but not Gt-i) invaded bovine and murine mammary epithelial cells (Mecs) and induced apoptosis, as determined by the terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labeling assay. this P. zopfii Gt-ii driven apoptosis corresponded to mitochondrial pathways; mitochondrial transmembrane resistance (ΔΨm) was altered and modulation of mitochondrionmediated apoptosis regulating genes changed (increased transcriptional Bax, cytochrome-c and Apaf-1 and downregulated Bcl-2), whereas caspase-9 and-3 expression increased. Apoptotic effects by P. zopfii Gt-ii were more pronounced in macrophages compared to Mecs. in a murine mammary infection model, P. zopfii GT-II replicated in the mammary gland and caused severe inflammation with infiltration of macrophages and neutrophils and upregulation of pro-inflammatory genes (TNF-α, IL-1β and Cxcl-1) and also apoptosis of epithelial cells. thus, we concluded P. zopfii Gt-ii is a mastitis-causing pathogen that triggers severe inflammation and also mitochondrial apoptosis.

Campylobacter is an important cause of foodborne gastroenteritis. We determined the occurrence of Campylobacter jejuni and Campylobacter coli, using culture-based methods and PCRs targeting virulence-associated genes (VAGs) among children aged ¡14 years who were treated for diarrhoea at emergency rooms in northeastern Brazil. Genomic DNA was extracted directly from stool samples collected from 366 children. A questionnaire was also applied to qualify the clinical conditions presented by each child at the time of admission. C. jejuni and C. coli were detected in 16.4 % (60/366) and 1.4 % (5/366) of the diarrhoeal samples, respectively, by PCR, a much higher proportion than that detected by conventional methods. C. jejuni VAGs were detected in the following proportions of hipO-positive samples: ciaB, 95 % (57/60); dnaJ, 86.7 % (52/60); racR, 98.3 % (59/60); flaA, 80 % (48/60); pldA, 45 % (27/60); cdtABC, 95 % (57/60); and pVir 0 % (0/ 60). Particular symptoms, such as blood in faeces, vomiting, fever, and/or abdominal pain, were not associated with detection of C. jejuni nor were they associated with any particular VAG or combination of VAGs (P.0.05). C. jejuni and its VAGs were detected in a substantial proportion of the children admitted. Further efforts shall be directed towards elucidating whether these genetic factors or their expressed proteins play a role in Campylobacter pathogenesis. INTRODUCTIONThe genus Campylobacter, a group of thermotolerant, microaerophilic, Gram-negative bacteria, includes a number of pathogens that primarily cause gastrointestinal disease in humans, particularly Campylobacter jejuni and Campylobacter coli. Campylobacter-associated gastroenteritis is thought to occur through zoonotic transmission, being acquired from exposure to tainted food and/or contaminated drinking water (Sherman et al., 2010). Campylobacter infection frequently presents as self-limiting acute enteritis with diarrhoea, malaise, fever and abdominal pain, sometimes with vomiting and the presence of blood in faeces (Allos, 2001); disruption of epithelial cells and inflammation of the intestinal mucosa are hallmark features of severe cases (Beltinger et al., 2008). C. jejuni and C. coli cause significant morbidity worldwide, especially in children (Amieva, 2005;Tam et al., 2003;Wang et al., 2008; Fernández et al., 2008).Adherence and colonization are crucial steps in the pathogenesis of C. jejuni. Flagella have a major role in invasion; markedly reduced internalization in vitro has been reported with flaA 2 C. jejuni mutants (Wassenaar, 1997). The genes racR and dnaJ are determinants for C. jejuni colonization and are presumably expressed in response to conditions encountered in the intestinal microenviroment, such as differences in temperature between environmental reservoirs and human intestines (Konkel et al., 1998; Brás et al., 1999 antigen B protein, which confers invasive properties, as shown by C. jejuni ciaB null mutants which display a significant reduction in internalization (Konkel et al., 1999). Also, ...

Malnutrition results in serious consequences for growth and cognitive development in children. We studied select child and maternal biological factors, socio-economic factors, enteric pathogenic burden, and gut function biomarkers in 402 children 6–24 months of age in North-eastern Brazil. In this prospective case-control study, not being fed colostrum (odds ratio [OR] = 3.29, 95% confidence interval [CI] 1.73–6.26), maternal age ≥18 years (OR = 1.88, 95% CI 1.10–3.22), and no electrical fan (OR = 2.46, 95% CI 1.22–4.96) or bicycle (OR = 1.80, 95% CI 1.10–2.95) in the household were positively associated, and higher birth weight (OR = 0.27, 95% CI 0.19–0.38), larger head circumference (OR = 0.74, 95% CI 0.66–0.82), and shortness of breath in the last two weeks (OR = 0.49, 95% CI 0.27–0.90) were negatively associated with malnutrition. Subclinical enteric pathogen infections were common, and enteroaggregative Escherichia coli infections were more prevalent in malnourished children (p = 0.045). Biomarkers such as the lactulose:mannitol test, myeloperoxidase, neopterin, and calprotectin were highly elevated in both malnourished and nourished children. Nourished children had a better systemic immune response than the malnourished children, as detected by elevated serum amyloid A-1 (SAA-1) and soluble cluster of differentiation protein 14 (sCD14) biomarkers (P < 0.001). SAA-1 and sCD14 were also associated with better nutritional z-scores. Neonatal, maternal, and socio-economic factors were associated with malnutrition in children. There was a substantial subclinical enteric pathogen burden, particularly with EAEC, in malnourished children.