James Dekker

Differential effects of two probiotics on the risks of eczema and atopy associated with single nucleotide polymorphisms to Toll‐like receptors

There is strong evidence to support a genetic predisposition to eczema and more recently studies have suggested that probiotics might be used to prevent eczema by modifying the expression of putative allergy‐associated genes. The aim of this present study was to investigate whether two probiotics, Lactobacillus rhamnosus HN001 (HN001) and Bifidobacterium animalis subsp. lactis HN019 (HN019), can modify the known genetic predisposition to eczema conferred by genetic variation in the Toll‐like receptor (TLR) genes in a high‐risk infant population.

Differential modification of genetic susceptibility to childhood eczema by two probiotics

In a double‐blind, randomized, placebo‐controlled birth cohort, we have recently shown a beneficial effect of Lactobacillus rhamnosus HN001 (HN001) for the prevention of eczema in children through to 6 years of age but no effect of Bifidobacterium animalis subsp lactis HN019 (HN019).

Altered Transcription of Murine Genes Induced in the Small Bowel by Administration of Probiotic Strain Lactobacillus rhamnosus HN001

ABSTRACT Lactobacillus rhamnosus HN001 is a probiotic strain reported to increase resistance to epithelium-adherent and -invasive intestinal pathogens in experimental animals. To increase understanding of the relationship between strain HN001 and the bowel, transcription of selected genes in the mucosa of the murine small bowel was measured. Mice previously naive to lactobacilli (Lactobacillus-free mice) were examined after daily exposure to HN001 in drinking water. Comparisons were made to results from matched Lactobacillus-free mice. Infant and adult mice were investigated to provide a temporal view of gene expression in response to exposure to HN001. Genes sgk1, angptl4, and hspa1b, associated with the apoptosis pathway, were selected for investigation by reverse transcription-quantitative PCR on the basis of a preliminary duodenal DNA microarray screen. Normalized to gapdh gene transcription, these three genes were upregulated after 6 to 10 days exposure of adult mice to HN001. Angptl4 was shown by immunofluorescence to be upregulated in duodenal epithelial cells of mucosal samples. Epithelial cell migration was faster in HN001-exposed mice than in the Lactobacillus-free controls. Transcriptional responses in infant mice differed according to bowel region and age. For example, sgk1 was upregulated in duodenal, jejunal, and ileal mucosa of mice less than 25 days old, whereas angptl4 and hspa1b were upregulated at 10 days in the duodenum but downregulated in the jejunal mucosa until mice were 25 days old. Overall, the results provide links between a probiotic strain, mucosal gene expression, and host phenotype, which may be useful in delineating mechanisms of probiotic action.

Integrated Role of Bifidobacterium animalis subsp. lactis Supplementation in Gut Microbiota, Immunity, and Metabolism of Infant Rhesus Monkeys

Probiotics are becoming increasingly popular due to their perceived effects on health, despite a lack of mechanistic information on how they impart these benefits. Infant formula and complementary foods are common targets for supplementation with probiotics. However, different probiotic strains have different properties, and there is a lack of data on long-term health effects on the consumer. Given the increasing interest in supplementation with probiotics and the fact that the gastrointestinal tracts of infants are still immature, we sought to determine whether consumption of infant formula containing the probiotic Bifidobacterium animalis subsp. lactis HN019 for 3 months starting at birth would impact gut microbial colonization, as well as infant immunity and metabolism, when compared with consumption of formula alone. ABSTRACT To investigate the impact of probiotic supplementation of infant formula on immune parameters, intestinal microbiota, and metabolism, five individually housed infant rhesus monkeys exclusively fed standard infant formula supplemented with probiotics (Bifidobacterium animalis subsp. lactis HN019) from birth until 3 months of age were compared with five standard formula-fed and five breast-fed monkeys. Anthropometric measurements, serum insulin, immune parameters, fecal microbiota, and metabolic profiles of serum, urine, and feces were evaluated. Consumption of B. lactis-supplemented formula reduced microbial diversity, restructured the fecal microbial community, and altered the fecal metabolome at the last two time points, in addition to increasing short-chain fatty acids in serum and urine. Circulating CCL22 was lower and threonine, branched-chain amino acids, urea, and allantoin, as well as dimethylglycine in serum and urine, were increased in the group supplemented with B. lactis compared with the standard formula-fed group. These results support a role of probiotics as effectors of gut microbial activity regulating amino acid utilization and nitrogen cycling. Future risk-benefit analyses are still needed to consolidate the existing knowledge on the long-term consequences of probiotic administration during infancy. IMPORTANCE Probiotics are becoming increasingly popular due to their perceived effects on health, despite a lack of mechanistic information on how they impart these benefits. Infant formula and complementary foods are common targets for supplementation with probiotics. However, different probiotic strains have different properties, and there is a lack of data on long-term health effects on the consumer. Given the increasing interest in supplementation with probiotics and the fact that the gastrointestinal tracts of infants are still immature, we sought to determine whether consumption of infant formula containing the probiotic Bifidobacterium animalis subsp. lactis HN019 for 3 months starting at birth would impact gut microbial colonization, as well as infant immunity and metabolism, when compared with consumption of formula alone.

Promotility Action of the Probiotic Bifidobacterium lactis HN019 Extract Compared with Prucalopride in Isolated Rat Large Intestine

Attention is increasingly being focussed on probiotics as potential agents to restore or improve gastrointestinal (GI) transit. Determining mechanism of action would support robust health claims. The probiotic bacterium Bifidobacterium lactis HN019 reduces transit time, but its mechanisms of action and effects on motility patterns are poorly understood. The aim of this study was to investigate changes in GI motility induced by an extract of HN019 on distinct patterns of colonic motility in isolated rat large intestine, compared with a known promotility modulator, prucalopride. The large intestines from male Sprague Dawley rats (3–6 months) were perfused with Krebs buffer at 37°C in an oxygenated tissue bath. Isometric force transducers recorded changes in circular muscle activity at four independent locations assessing contractile propagation between the proximal colon and the rectum. HN019 extract was perfused through the tissue bath and differences in tension and frequency quantified relative to pre-treatment controls. Prucalopride (1 μM) increased the frequency of propagating contractions (by 75 ± 26%) in the majority of preparations studied (10/12), concurrently decreasing the frequency of non-propagating contractions (by 50 ± 11%). HN019 extract had no effect on contractile activity during exposure (n = 8). However, following wash out, contraction amplitude of propagating contractions increased (by 55 ± 18%) in the distal colon, while the frequency of non-propagating proximal contractions decreased by 57 ± 7%. The prokinetic action of prucalopride increased the frequency of synchronous contractions along the length of colon, likely explaining increased colonic rate of transit in vivo. HN019 extract modified motility patterns in a different manner by promoting propagating contractile amplitude and inhibiting non-propagations, also demonstrating prokinetic activity consistent with the reduction of constipation by B. lactis HN019 in humans.

Colostrum from Cows Immunized with a Vaccine Associated with Bovine Neonatal Pancytopenia Contains Allo-Antibodies that Cross-React with Human MHC-I Molecules

In 2006, a new haemorrhagic syndrome affecting newborn calves, Bovine Neonatal Pancytopenia (BNP), was reported in southern Germany. It is characterized by severe bleeding, destruction of the red bone marrow, and a high case fatality rate. The syndrome is caused by alloreactive, maternal antibodies that are ingested by the calf with colostrum and result from a dam vaccination with one particular vaccine against Bovine-Viral-Diarrhoea-Virus. Because bovine colostrum is increasingly gaining interest as a dietary supplement for human consumption, the current study was initiated to elucidate whether BNP alloantibodies from BNP dams (i.e. animals that gave birth to a BNP-affected calf) cross-react with human cells, which could pose a health hazard for human consumers of colostral products. The present study clearly demonstrates that BNP alloantibodies cross-react with human lymphocytes in vitro. In agreement with previous reports on BNP, the cross-reactive antibodies are specific for MHC-I molecules, and sensitize opsonised human cells for in vitro complement lysis. Cross-reactive antibodies are present in serum and colostrum of individual BNP dams. They can be traced in commercial colostrum powder manufactured from cows immunized with the vaccine associated with BNP, but are absent from commercial powder manufactured from colostrum excluding such vaccinated cows. In humans alloreactive, MHC-I specific antibodies are generally not believed to cause severe symptoms. However, to minimize any theoretical risk for human consumers, manufacturers of bovine colostrum for human consumption should consider using only colostrum from animals that have not been exposed to the vaccine associated with BNP.