Bifidobacterium lactis attenuates onset of inflammation in a murine model of colitis

To assess the anti-inflammatory effect of the probiotic Bifidobacterium lactis (B. lactis) in an adoptive transfer model of colitis

Oral application of Escherichia coli bacteriophage: safety tests in healthy and diarrheal children from Bangladesh

A T4-like coliphage cocktail was given with different oral doses to healthy Bangladeshi children in a placebo-controlled randomized phase I safety trial. Fecal phage detection was oral dose dependent suggesting passive gut transit of coliphages through the gut. No adverse effects of phage application were seen clinically and by clinical chemistry. Similar results were obtained for a commercial phage preparation (Coliproteus from Microgen/Russia). By 16S rRNA gene sequencing, only a low degree of fecal microbiota conservation was seen in healthy children from Bangladesh who were sampled over a time interval of 7 days suggesting a substantial temporal fluctuation of the fecal microbiota composition. Microbiota variability was not associated with the age of the children or the presence of phage in the stool. Stool microbiota composition of Bangladeshi children resembled that found in children of other regions of the world. Marked variability in fecal microbiota composition was also seen in 71 pediatric diarrhea patients receiving only oral rehydration therapy and in 38 patients receiving coliphage preparations or placebo when sampled 1.2 or 4 days apart respectively. Temporal stability of the gut microbiota should be assessed in case-control studies involving children before associating fecal microbiota composition with health or disease phenotypes

Linking Human Milk Oligosaccharides, Infant Fecal Community Types, and Later Risk To Require Antibiotics

Human milk is the sole and recommended nutrition for the newborn infant and contains one of the largest constituents of diverse oligosaccharides, dubbed human milk oligosaccharides (HMOs). Preclinical and clinical association studies indicate that HMOs have multiple physiological functions largely mediated through the establishment of the gut microbiome. Until recently, HMOs were not available to investigate their role in randomized controlled intervention trials. To our knowledge, this is the first report on the effects of 2 HMOs on establishing microbiota in newborn infants. We provide a detailed description of the microbiota changes observed upon feeding a formula with 2 HMOs in comparison to breastfed reference infants' microbiota. Then, we associate the microbiota to long-term health as assessed by prescribed antibiotic use.Human milk oligosaccharides (HMOs) may provide health benefits to infants partly by shaping the development of the early-life intestinal microbiota. In a randomized double-blinded controlled multicentric clinical trial, healthy term infants received either infant formula (control) or the same formula with two HMOs (2′-fucosyllactose and lacto-N-neotetraose; test) from enrollment (0 to 14 days) to 6 months. Then, all infants received the same follow-up formula without HMOs until 12 months of age. Breastfed infants (BF) served as a reference group. Stool microbiota at 3 and 12 months, analyzed by 16S rRNA gene sequencing, clustered into seven fecal community types (FCTs) with marked differences in total microbial abundances. Three of the four 12-month FCTs were likely precursors of the adult enterotypes. At 3 months, microbiota composition in the test group (n = 58) appeared closer to that of BF (n = 35) than control (n = 63) by microbiota alpha (within group) and beta (between groups) diversity analyses and distribution of FCTs. While bifidobacteriaceae dominated two FCTs, its abundance was significantly higher in one (FCT BiH for Bifidobacteriaceae at high abundance) than in the other (FCT Bi for Bifidobacteriaceae). HMO supplementation increased the number of infants with FCT BiH (predominant in BF) at the expense of FCT Bi (predominant in control). We explored the association of the FCTs with reported morbidities and medication use up to 12 months. Formula-fed infants with FCT BiH at 3 months were significantly less likely to require antibiotics during the first year than those with FCT Bi. Previously reported lower rates of infection-related medication use with HMOs may therefore be linked to gut microbiota community types. (This study has been registered at ClinicalTrials.gov under registration number NCT01715246.

The mouse microbiome is required for sex-specific diurnal rhythms of gene expression and metabolism

The circadian clock and associated feeding rhythms have a profound impact on metabolism and the gut microbiome. To what extent microbiota reciprocally affect daily rhythms of physiology in the host remains elusive. Here, we analyzed transcriptome and metabolome profiles of male and female germ-free mice. While mRNA expression of circadian clock genes revealed subtle changes in liver, intestine, and white adipose tissue, germ-free mice showed considerably altered expression of genes associated with rhythmic physiology. Strikingly, the absence of the microbiome attenuated liver sexual dimorphism and sex-specific rhythmicity. The resulting feminization of male and masculinization of female germ-free animals is likely caused by altered sexual development and growth hormone secretion, associated with differential activation of xenobiotic receptors. This defines a novel mechanism by which the microbiome regulates host metabolism

Impact of consumption of the human milk oligosaccharides 2′-FL and LNnT on reduction of risk of allergic sensitisation

ABSTRACTHuman Milk Oligosaccharides (HMOs) have been proposed to be instrumental in building immune competence. To explore the role of HMOs in allergy prevention, twenty-one HMOs were quantified in breast milk samples and associated with sensitisation in infants. 2′-fucosyllactose (2′-FL) levels were positively associated with an increased risk of sensitisation, atopic dermatitis and recurrent skin rash. Interestingly, 2′-FL levels, ranging from 1.35 to 1.95 g/L, were associated with a higher prevalence of non-allergic and non-sensitised infants. The role of 2′-FL and lacto-N-neotetraose (LNnT) was further investigated in allergic sensitisation models in vivo. Oral administration of HMOs decreased allergic sensitisation. This was associated with gut microbiota and short-chain fatty acid (SCFA) production changes. Aligned with the clinical associations, the decreased sensitisation was not observed with lower and higher tested doses of the HMOs supporting a U-shape association between 2′-FL and LNnT levels and allergic sensitisation risk reduction in humans and mice.Trial registration: ClinicalTrials.gov identifier: NCT02550236

Impact of consumption of the human milk oligosaccharides 2′-FL and LNnT on reduction of risk of allergic sensitisation

Human Milk Oligosaccharides (HMOs) have been proposed to be instrumental in building immune competence. To explore the role of HMOs in allergy prevention, twenty-one HMOs were quantified in breast milk samples and associated with sensitisation in infants. 2′-fucosyllactose (2′-FL) levels were positively associated with an increased risk of sensitisation, atopic dermatitis and recurrent skin rash. Interestingly, 2′-FL levels, ranging from 1.35 to 1.95 g/L, were associated with a higher prevalence of non-allergic and non-sensitised infants. The role of 2′-FL and lacto-N-neotetraose (LNnT) was further investigated in allergic sensitisation models in vivo. Oral administration of HMOs decreased allergic sensitisation. This was associated with gut microbiota and short-chain fatty acid (SCFA) production changes. Aligned with the clinical associations, the decreased sensitisation was not observed with lower and higher tested doses of the HMOs supporting a U-shape association between 2′-FL and LNnT levels and allergic sensitisation risk reduction in humans and mice. Trial registration:ClinicalTrials.gov identifier: NCT02550236.</p