Kurt Zimmermann

A vegan or vegetarian diet substantially alters the human colonic faecal microbiota

Background/Objectives:Consisting of ∼1014 microbial cells, the intestinal microbiota represents the largest and the most complex microbial community inhabiting the human body. However, the influence of regular diets on the microbiota is widely unknown.Subjects/Methods:We examined faecal samples of vegetarians (n=144), vegans (n=105) and an equal number of control subjects consuming ordinary omnivorous diet who were matched for age and gender. We used classical bacteriological isolation, identification and enumeration of the main anaerobic and aerobic bacterial genera and computed absolute and relative numbers that were compared between groups.Results:Total counts of Bacteroides spp., Bifidobacterium spp., Escherichia coli and Enterobacteriaceae spp. were significantly lower (P=0.001, P=0.002, P=0.006 and P=0.008, respectively) in vegan samples than in controls, whereas others (E. coli biovars, Klebsiella spp., Enterobacter spp., other Enterobacteriaceae, Enterococcus spp., Lactobacillus spp., Citrobacter spp. and Clostridium spp.) were not. Subjects on a vegetarian diet ranked between vegans and controls. The total microbial count did not differ between the groups. In addition, subjects on a vegan or vegetarian diet showed significantly (P=0.0001) lower stool pH than did controls, and stool pH and counts of E. coli and Enterobacteriaceae were significantly correlated across all subgroups.Conclusions:Maintaining a strict vegan or vegetarian diet results in a significant shift in the microbiota while total cell numbers remain unaltered.

Establishment of the intestinal microbiota and its role for atopic dermatitis in early childhood

BACKGROUNDnPerturbations in the intestinal microbiota may disrupt mechanisms involved in the development of immunologic tolerance. The present study aimed to examine the establishment of the infant microbiota and its association to the development of atopic dermatitis (AD).nnnMETHODSnWithin a randomized, placebo-controlled trial on the prevention of AD by oral supplementation of a bacterial lysate between week 5 and the end of month 7, feces was collected at the ages of 5 weeks (n = 571), 13 weeks (n = 332), and 31 weeks (n = 499) and subjected to quantitative PCRs to detect bifidobacteria, bacteroides, lactobacilli, Escherichia coli, Clostridium difficile, and Clostridium cluster I.nnnRESULTSnBirth mode, breast-feeding but also birth order had a strong effect on the microbiota composition. With increasing number of older siblings the colonization rates at age 5 weeks of lactobacilli (P < .001) and bacteroides (P = .02) increased, whereas rates of clostridia decreased (P < .001). Colonization with clostridia, at the age of 5 and 13 weeks was also associated with an increased risk of developing AD in the subsequent 6 months of life (odds ratioadjusted = 2.35; 95% CI, 1.36-3.94 and 2.51; 1.30-4.86, respectively). Mediation analyses demonstrated that there was a statistically significant indirect effect via Clostridium cluster I colonization for both birth mode and birth order in association to AD.nnnCONCLUSIONnThe results of this study are supportive for a role of the microbiota in the development of AD. Moreover, the beneficial influence of older siblings on the microbiota composition suggests that this microbiota may be one of the biological mechanisms underlying the sibling effect.

Oral application of bacterial lysate in infancy decreases the risk of atopic dermatitis in children with 1 atopic parent in a randomized, placebo-controlled trial.

BACKGROUNDnLower prevalence of atopy was found in children with continuous exposure to livestock and thus to microbial compounds. In animal models exposure to endotoxin (LPS) decreases allergic sensitization and airway inflammation.nnnOBJECTIVEnWe sought to evaluate the effect of orally applied bacterial lysate in infancy on the prevalence of atopic dermatitis (AD) after the treatment phase at 7 months of age.nnnMETHODSnThis randomized, placebo-controlled trial included 606 newborns with at least single heredity for atopy. From week 5 until the end of month 7, infants were treated orally with bacterial lysate containing heat-killed gram-negative Escherichia coli Symbio and gram-positive Enterococcus faecalis Symbio or its placebo. Children were followed until 3 years of age.nnnRESULTSnThere was no difference in the primary outcome between the active and placebo groups in the total study group. AD prevalence was significantly reduced at the end of the intervention phase (31 weeks of age) in the subgroup of infants with single heredity for atopy (relative risk, 0.52; 95% CI, 0.3-0.9). Ten percent (15/154) of infants in the active group had AD compared with 19% (27/145, P = .030) in the placebo group. This was more pronounced in the group of infants with paternal heredity for atopy (11% vs 32%, P = .004; relative risk, 0.34; 95% CI, 0.2-0.7).nnnCONCLUSIONnFeeding of bacterial lysate might have prevented the development of AD, especially in children with paternal atopy, possibly indicating a preventive property only in subjects with a limited risk for atopy.

Randomized Controlled Treatment Trial of Irritable Bowel Syndrome with a Probiotic E.-coli Preparation (DSM17252) Compared to Placebo.

BACKGROUNDnTherapy trials with bacterial compounds in irritable bowel syndrome (IBS) have produced conflicting results and, so far, an E.-coli preparation has not been used.nnnMETHODSnTwo hundred and ninety-eight patients with lower abdominal symptoms diagnosed as IBS were treated for 8 weeks by the compound Symbioflor-2 (Symbiopharm GmbH, Herborn, Germany), an Escherichia coli product (N = 148), or placebo (n = 150) in a double-blinded, randomized fashion. Patients were seen weekly by the physician, who assessed the presence of core IBS symptoms. Both an abdominal pain score (APS) as well as a general symptom score (GSS) were used as primary endpoints. Responders had to have complete absence of IBS core symptoms at > or = 1 visit during treatment.nnnRESULTSnThe responder rate in GSS to the drug was 27 / 148 (18.2 %) in comparison to placebo with 7 / 150 (4.67 %) (p = 0.000397). The improvement in APS was 28 / 148 (18.9 %) and 10 / 150 (6.67 %) for placebo (p = 0.001649). The response was reached from visit 3 onwards with both medication and placebo. Post-hoc analysis revealed no significant differences in efficacy of the drug between the gender and different age groups.nnnCONCLUSIONnTreatment of IBS with the probiotic Symbioflor-2 is effective and superior to placebo in reducing typical symptoms of IBS patients seen by general practitioners and by gastroenterologists.

The effects of ageing on the colonic bacterial microflora in adults.

BACKGROUNDnThe composition of the fecal mircoflora and its changes on ageing have rarely been investigated in large samples of both patients and volunteers.nnnMETHODSnWe analysed the fecal flora by conventional microbiological testing (Kyberstatus, Institute of Microecology, Herborn, Germany) of stool samples from 35 292 adults (age: 46.3 +/- 0.08 [18 to 96] years, 9564 males, 24 784 females; remaining = missing data) with different intestinal and non-intestinal diagnoses for total colony-forming units (CFU) (per g stool) as well as relative abundance of Bifidobacteria, Bacteroides spp., Escherichia coli, Enterococcus spp., and Lactobacillus spp. with respect to age, gender, and clinical data available (e. g., stool consistency and pH).nnnRESULTSnThe total CFU was stable and showed no age- or gender-related changes. Individual bacterial species constantly and significantly increased with age (E. coli, Enterococci spp.), or decreased at higher age (Bacteroides spp.), or were stable throughout the life span (Lactobacilli, Bifidobacteria). Gastrointestinal diagnoses (Crohns disease, n = 198; ulcerative colitis, n = 515; irritable bowel syndrome, n = 7765; other GI diagnoses, n = 10 478) tended to exhibit some specificity of the bacterial profile, and when GI diagnoses were excluded, the age-related bacterial profile of the remaining group (n = 15 619, m:f = 4197:11 422) was not different.nnnCONCLUSIONnConventional microbiological investigations of the fecal microbiota showed both bacteria-specific as well as a general pattern of ageing of the colonic microbiota, with the last decades (more than 60 years) demonstrating the most profound changes. It remains to be shown whether these changes reflect direct changes of the gut microbiota, the mucosal innate immunity, or indirect consequences of age-related altered nutrition.

New insights into the hygiene hypothesis in allergic diseases: Mediation of sibling and birth mode effects by the gut microbiota

There is convincing evidence from both human and animal studies suggesting that the infant intestinal microbiota plays an important role in regulating immune responses associated with the development of allergic diseases. To date there are, however, still no definite bacterial taxa or particular subsets of the microbiota that have been consistently associated with allergic diseases, which is mainly attributable to the methodological dissimilarities between studies. As such there is a need to apply different methodological concepts to enhance a deeper and more refined understanding of the relationship between the gut microbiota and allergies. Within our recent studies we reported that colonization by clostridia in early infancy increased the risk of atopic dermatitis. Using subsequent mediation analysis, we demonstrated that birth mode and having older siblings strongly impacted the infant microbiota which in turn affected the risk of atopic dermatitis. The results of these mediation analyses contributed stronger evidence for a causal link of birth mode and birth order on allergy risk through modulation of the microbiota composition.

Weight gain in anorexia nervosa does not ameliorate the faecal microbiota, branched chain fatty acid profiles, and gastrointestinal complaints

The gut microbiota not only influences host metabolism but can also affect brain function and behaviour through the microbiota-gut-brain axis. To explore the potential role of the intestinal microbiota in anorexia nervosa (AN), we comprehensively investigated the faecal microbiota and short-chain fatty acids in these patients before (nu2009=u200955) and after weight gain (nu2009=u200944) in comparison to normal-weight participants (NW, nu2009=u200955) along with dietary intake and gastrointestinal complaints. We show profound microbial perturbations in AN patients as compared to NW participants, with higher levels of mucin-degraders and members of Clostridium clusters I, XI and XVIII and reduced levels of the butyrate-producing Roseburia spp. Branched-chain fatty acid concentrations, being markers for protein fermentation, were elevated. Distinct perturbations in microbial community compositions were observed for individual restrictive and binge/purging AN-subtypes. Upon weight gain, microbial richness increased, however perturbations in intestinal microbiota and short chain fatty acid profiles in addition to several gastrointestinal symptoms did not recover. These insights provide new leads to modulate the intestinal microbiota in order to improve the outcomes of the standard therapy.

The Effects of Maturation on the Colonic Microflora in Infancy and Childhood

The composition of colonic mircoflora and its changes with maturation have rarely been investigated in large samples. Methods. We used conventional microbiological testing to analyse the colonic flora (Kyberstatus, Institut forMicroecology, Herborn, Germany) of stool samples from 12 484 children with different intestinal and nonintestinal diagnoses. Stool samples were analysed for total colony forming units (CFU) (per g stool) and the abundance of Bifidobacteria, Bacteroides sp., Escherichia coli, Enterococcus sp., and Lactobacillus sp. with respect to age, gender. A subset of 1089 infants was analysed for monthly changes within the first year of life. Results. Total CFU and individual microbial species were highest during the first year of life, decreased within the first 2 years, and then stabilized for the remaining childhood. In infants, the total CFU rose until month 5, declined with weaning, and peaked at 9–10 months. Significant effects of age, but not of gender, were found in Bacteroides sp. and Lactobacilli. However Bacterioids sp. and Lactobacilli increased with age, while Enterococci and E. coli decreased, and Bifidobacteria remained stable. Conclusion. Colonic microflora show both a bacteria-specific and general pattern of maturation which is most profound within the first year.

PD06 - Early elevated blood eosinophils are predictive for the development of atopic dermatitis in an atopic birth cohort

At 4 weeks of life and 7 months of life, respectively, 233/ 559 and 107/467 infants showed elevated blood eosinophils counts in the total study group. Elevated blood eosinophils observed at 4 weeks were significantly associated with the occurrence of AD in the whole study group at the time points 7 months (p =0.0073), one year (p=0.0035), two years (p=0.0069) and three years (p=0.006) of life. This observation was seen in the active group as well as the placebo treated group. Blood eosinophil counts at 7 months of life showed only borderline significance for developing AD (p=0.06) at the same age, and blood eosinophil counts at one year of life showed no association with AD. Conclusion Elevated blood eosinophils at age 4 weeks of life seem to be of predictive value for the onset of atopic dermatitis in infancy and early childhood in a high risk birth cohort. Eosinophil counts later in infancy were less correlated with AD prevalence. Early eosinophil counts can therefore be helpful for counseling the parents but furthermore can identify target groups for interventional trials aiming at allergy prevention.