Human milk oligosaccharides (HMO) and prebiotic oligosaccharides are proposed to confer several health benefits to the infant. They shape the microbiota, have anti-inflammatory properties, and ...support epithelial barrier functioning. However, in order to select the best oligosaccharides for inclusion in infant formulas, there is a need to increase our understanding of the specific effects of HMO and prebiotics on the host immune system. Therefore, we investigated the effects of the HMO sialyllactose (SL), and galactooligosaccharides (GOS) on epithelial barrier functioning, microbiota composition, and SCFA production. The effect of GOS and SL on epithelial barrier functioning and microbiota composition was investigated using
models. Epithelial barrier function was investigated by transcriptome analysis of fully polarized Caco-2 cells exposed for 6 h to SL or GOS. In addition, epithelial cell growth, alkaline phosphatase production, and re-epithelization was studied. Further, we investigated the effect of SL and GOS on microbiota composition and SCFA production using
fecal batch cultures. Transcriptome analysis showed that SL and GOS both induced pathways that regulate cell cycle control. This gene-expression profile translated to a phenotype of halted proliferation and included the induction of alkaline phosphatase activity, a marker of epithelial cell differentiation. SL and GOS also promoted re-epithelialization in an
epithelial wound repair assay. SL and GOS did show distinct modulation of microbiota composition, promoting the outgrowth of
and bifidobacteria, respectively, which resulted in distinct changes in SCFA production profiles. Our results show that SL and GOS can both modulate epithelial barrier function by inducing differentiation and epithelial wound repair, but differentially promote the growth of specific genera in the microbiota, which is associated with differential changes in SCFA profiles.
A good definition of commensal microflora and an understanding of its relation to health are essential in preventing and combating disease. We hypothesized that the species richness of human oral ...microflora is underestimated. Saliva and supragingival plaque were sampled from 71 and 98 healthy adults, respectively. Amplicons from the V6 hypervariable region of the small-subunit ribosomal RNA gene were generated by PCR, pooled into saliva and plaque pools, and sequenced by means of the Genome Sequencer 20 system at 454 Life Sciences. Data were evaluated by taxonomic and rarefaction analyses. The 197,600 sequences generated yielded about 29,000 unique sequences, representing 22 taxonomic phyla. Grouping the sequences in operational taxonomic units (6%) yielded 3621 and 6888 species-level phylotypes in saliva and plaque, respectively. This work gives a radically new insight into the diversity of human oral microflora, which, with an estimated number of 19,000 phylotypes, is considerably higher than previously reported.
In the present double-blind, randomised, parallel intervention study, the effects of the intake of galacto-oligosaccharides (GOS) on the gut microbiota of twelve healthy adult subjects (aged 18–45 ...years with a normal BMI (18–25 kg/m2)) receiving amoxicillin (AMX) treatment were determined. All the subjects were treated with AMX (375 mg; three times per d) for 5 d and given either GOS (n 6) or placebo (maltodextrin, n 6) (2·5 g; three times per d) during and 7 d after AMX treatment. Faecal samples were collected twice before starting the treatment and on days 2, 5, 8, 12, 19 and 26. Due to AMX treatment, a decrease in the abundance of Bifidobacterium spp., an overgrowth of Enterobacteriaceae, and a disruption of the metabolic activity of the microbiota (increase in succinate, monosaccharide and oligosaccharide levels in the faecal samples) were observed in both groups (P< 0·05). Positive effects of GOS intake were observed on the levels of bifidobacteria, although not found to be significant. Data revealed that the levels of bifidobacteria were higher upon GOS intake than upon placebo intake, especially after AMX treatment. The activity of bifidobacteria and subsequent cross-feeding activity of the microbiota upon GOS intake compared with those upon placebo intake were reflected by the significant increase in butyrate levels (P< 0·05) in the faecal samples after AMX treatment. Despite the small number of subjects, our findings confirm previous results obtained in vitro, namely that GOS intake supports the recovery of the beneficial bifidobacteria and, indirectly, the production of butyrate after AMX treatment.
Summary
Background
Alterations of the skin microbiome have been associated with atopic dermatitis (AD) and its severity. The nasal microbiome in relation to AD severity is less well studied.
...Objectives
We aimed to characterize the nasal and skin microbiomes in children with AD in relation to disease severity. In addition, we explored the differences and correlations between the nasal and skin communities.
Methods
We characterized the microbial composition of 90 nasal and 108 lesional skin samples cross‐sectionally from patients with AD, using 16S‐rRNA sequencing. In addition, a quantitative polymerase chain reaction was performed for Staphylococcus aureus and Staphylococcus epidermidis on the skin samples, and AD severity was estimated using the self‐administered Eczema Area and Severity Index.
Results
We found an association between the microbial composition and AD severity in both the nose and skin samples (R2 = 2·6%; P = 0·017 and R2 = 7·0%; P = 0·004), strongly driven by staphylococci. However, other species also contributed, such as Moraxella in the nose. Skin lesions were positive for S. aureus in 50% of the children, and the presence and the load of S. aureus were not associated with AD severity. Although the nose and skin harbour distinct microbial communities (n = 48 paired samples; P < 0·001), we found that correlations exist between species in the nose and (other) species on the skin.
Conclusions
Our results indicate that both the nasal and the skin microbiomes are associated with AD severity in children and that, next to staphylococci, other species contribute to this association.
What's already known about this topic?
Changes in the skin microbiome have been associated with atopic dermatitis (AD) and its severity.
Although the anterior nares could be an important reservoir for self‐contamination and bacterial spread from the nose to the skin or vice versa, research on the relation between the skin and nasal microbiome in AD is limited.
What does this study add?
Both the nasal and the skin microbiome are associated with the severity of AD in children.
Next to staphylococci, other species contribute to the association between the microbiome and AD severity.
Linked Comment: Clausen and Agner. Br J Dermatol 2019; 181:661–662.
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Antibiotic treatments can lead to a disruption of the human microbiota. In this in-vitro study, the impact of antibiotics on adult intestinal microbiota was monitored in a new high-throughput ...approach: a fermentation screening-platform was coupled with a phylogenetic microarray analysis (Intestinal-chip). Fecal inoculum from healthy adults was exposed in a fermentation screening-platform to seven widely-used antibiotics during 24h in-vitro fermentation and the microbiota composition was subsequently determined with the Intestinal-chip.
Phylogenetic microarray analysis was first verified to be reliable with respect to variations in the total number of bacteria and presence of dead (or inactive) cells. Intestinal-chip analysis was then used to identify and compare shifts in the intestinal microbial composition after exposure to low and high dose (1μgml−1 and 10μgml−1) antibiotics. Observed shifts on family, genus and species level were both antibiotic and dose dependent. Stronger changes in microbiota composition were observed with higher doses. Shifts mainly concerned the bacterial groups Bacteroides, Bifidobacterium, Clostridium, Enterobacteriaceae, and Lactobacillus. Within bacterial groups, specific antibiotics were shown to differentially impact related species.
The combination of the in-vitro fermentation screening platform with the phylogenetic microarray read-outs has shown to be reliable to simultaneously analyze the effects of several antibiotics on intestinal microbiota.
► Fermentation screening-platform successfully coupled to a microarray analysis ► Microarray provides reliable in-sights on antibiotic impact on the microbiota. ► Seven widely-used antibiotics affect adult intestinal microbiota differently. ► Even sub-MIC dose of antibiotics alters the microbiota composition.
To the Editor: Staphylococcus aureus density is increased in many patients with atopic dermatitis (AD) and is thought to contribute to disease pathogenesis, interacting with an altered skin barrier ...and immunologic changes.1 S aureus might induce or aggravate inflammation through different mechanisms, for example through excretion of virulence factors, even if the S aureus overgrowth is primarily caused by other factors.2 Current guidelines only recommend antimicrobial therapy directed against S aureus in patients with clinically infected AD based on a Cochrane review in which no clinical benefit of short-term antimicrobial treatment in patients with noninfected AD was found.3 Arguably, long-term antistaphylococcal treatment, such as antibiotics, might reduce symptoms in patients with AD.4 However, this is undesired because antibiotics can affect the commensal microbiota and could induce bacterial resistance.5 In contrast, long-term treatment of AD with an endolysin that targets only S aureus is feasible. Clinical efficacy was measured by using the Eczema Area and Severity Index, Investigators Global Assessment, Patient-Oriented Eczema Measure, and pruritus Numeric Rating Scale and by registration of the number of flares. ...daily use of an emollient and good compliance with the treatment could have resulted in a reduction in triamcinolone use in both the endolysin and vehicle groups.7 Because AD is a heterogeneous disease, anti–S aureus treatment might not be suitable for all patients with AD, indicating the need for subphenotyping. Because only 56% of our study population had 2 consecutive positive S aureus skin cultures (indicating persistent colonization) before the start of the intervention, the target population that would probably benefit the most from endolysin treatment was small. ...long-term targeted endolysin treatment against S aureus in this study was well tolerated but had no TCS-sparing effect in patients with AD.
Colon microbiota-based drug metabolism has received little attention thus far in the process of drug development, whereas the role of gut microbiota in clinical safety and efficacy of drugs has ...become more clear. Many of these studies have been performed using animal studies, but the translational value of these data with respect to drug pharmacokinetics, efficacy, and safety is largely unknown. To investigate human colon microbiota-mediated drug metabolism, we applied a recently developed ex vivo fermentation screening platform, in which human colonic microbiota conditions are simulated. A set of 12 drugs (omeprazole, simvastatin, metronidazole, risperidone, sulfinpyrazone, sulindac, levodopa, dapsone, nizatidine, sulfasalazine, zonisamide, and acetaminophen) was incubated with human colon microbiota under strictly anaerobic conditions, and samples were analyzed using high-performance liquid chromatograph-UV-high-resolution mass spectrometry analysis. The human microbiota in the fermentation assay consisted of bacterial genera regularly encountered in human colon and fecal samples and could be reproducibly cultured in independent experiments over time. In addition, fully anaerobic culture conditions could be maintained for 24 hours of incubation. Five out of the 12 included drugs (sulfasalazine, sulfinpyrazone, sulindac, nizatidine, and risperidone) showed microbiota-based biotransformation after 24 hours of incubation in the ex vivo fermentation assay. We demonstrated that drug metabolites formed by microbial metabolism can be detected in a qualitative manner and that the data are in accordance with those reported earlier for in vivo metabolism. In conclusion, we present a research tool to investigate human colon microbiota-based drug metabolism that may be applied to enable translatability of microbiota-based drug metabolism.
Background
The skin microbiome, characterized by an overgrowth of Staphylococcus aureus, plays an important role in the pathogenesis of atopic dermatitis (AD). Multidisciplinary treatment in alpine ...climate is known for its positive effect on disease severity in children with AD and can result in a different immune response compared with moderate maritime climate. However, the effect on the composition of the skin microbiome in AD is unknown.
Objective
To determine the effect of treatment in alpine climate and moderate maritime climate on the microbiome for lesional and non‐lesional skin in children with difficult to treat AD.
Results
Alpine climate treatment led to a significant change in the microbiota on lesional skin, whereas no significant change was found after moderate maritime climate. On both lesional and non‐lesional skin, we observed a significant increase in Shannon diversity and a significant decrease in both Staphylococcus abundance and S aureus load after alpine climate treatment. The decrease in S aureus was significantly larger on lesional skin following alpine climate treatment compared with moderate maritime climate treatment. Staphylococcus epidermidis load was stable over time.
Conclusions and clinical relevance
Alpine climate treatment leads to significant changes in the composition of the skin microbiome in children with AD, mainly caused by a reduction in the Staphylococcus genus. This study shows new perspectives in the potential mode of action for therapies in AD.
Microbiota plays a role in the release and absorption of nutrients from feed components, thereby affecting digesta composition and moisture content of the excreta. The objective of the current study ...was to determine the effects of 5 different diets varying in ingredients (medium-chain fatty acids, nonstarch polysaccharides, and starch) on the microbiota composition of ileal digesta of broiler chickens and excreta DM content. Each treatment was repeated 6 times in cages each containing 18 Ross 308 broilers, with growth performance measured from 0 to 34 d of age and excreta DM and ileal microbiota composition analyzed at 34 d of age. Microbiota composition was evaluated using a novel ribosomal RNA microarray technology containing 370 different probes covering various genera, groups of microbial species, and individual species of the chicken gut microbiota, of which 321 had a signal above the background threshold. Replacing part of the animal fat and soybean oil in the wheat-based diet with medium-chain fatty acids (MCFA; 0.3% C10 and 2.7% C12) improved feed efficiency compared with the other dietary treatments. This coincided with a suppression of gram-positive bacteria belonging to the phylum of the Firmicutes, including Lactobacillus species, and species belonging to the family of the Enterococcaceae and Micrococcaceae, whereas the gram-negative bacteria belonging to the family of the Enterobacteriaceae were promoted. None of the other diets used in the present study notably changed the ileal digesta bacteria composition. Excreta DM content was not affected by dietary treatment. The variation between individual birds per dietary treatment was more pronounced than variation caused by feed composition, with the exception of the digesta microbiota of the birds fed the MCFA diet. It is concluded that a diet with MCFA significantly changes the ileal microbiota composition, whereas the effect of the other diets on the composition of the microbiota and excreta DM content is small in broiler chickens.
Atopic dermatitis (AD) is a chronic inflammatory skin disease that affects 10 to 20% of children and between 2 and 15% of the adults in Western Europe. Since 2000, therapeutic clothing or functional ...textiles based on silver or chitosan as antibacterial agents were introduced for AD. These agents aim to reduce skin colonization with Staphylococcus (S.) aureus. Increased colonization with S. aureus is correlated with increased AD severity. The antimicrobial effects of silver and chitosan have been demonstrated before. At this point, there is insufficient evidence for the effectiveness of antibacterial therapeutic clothing in patients with AD.
This is a pragmatic randomized controlled double-blind multi-center trial comparing the effectiveness of antibacterial therapeutic clothing based on silver or chitosan as compared with non-antibacterial therapeutic clothing in patients with moderate to severe AD. A total of 165 participants, aged 0 to 80, diagnosed with moderate to severe AD are included. The study is performed in the Erasmus MC University Medical Center, University Medical Center Groningen, University Medical Center Utrecht, Amsterdam University Medical Centers, and St. Antonius Hospital Nieuwegein. Patients will be randomized 1:1:1 into one of the three intervention groups: group A will receive therapeutic clothing without antimicrobial agents, group B will receive microbial growth reducing therapeutic clothing based on chitosan, and group C will receive antimicrobial clothing based on silver. All therapeutic clothing is to be worn at night during the 12-month intervention period. Usual care is continued. The primary objective is to assess the effectiveness of antibacterial clothing (silver and chitosan group) as compared to non-antibacterial clothing assessed with the Eczema Area and Severity Index at 12 months compared to baseline. Secondary outcomes include between-group differences in physician- and patient-reported outcome measures, topical therapy use, S. aureus skin colonization, and safety. Data will be collected at baseline and after 1 month, 3 months, 6 months, and 12 months. A cost-effectiveness analysis will be performed.
This trial will provide data on the effectiveness, cost-effectiveness, and safety of antibacterial therapeutic clothing for patients with AD.
ClinicalTrials.gov NCT04297215. Registered on 5 March 2020.
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