[Crohn's disease].

ABSTRACT The human intestine hosts diverse microbial communities that play a significant role in maintaining gut-skin homeostasis. When the relationship between gut microbiome and the immune system is impaired, subsequent effects can be triggered on the skin, potentially promoting the development of skin diseases. The mechanisms through which the gut microbiome affects skin health are still unclear. Enhancing our understanding on the connection between skin and gut microbiome is needed to find novel ways to treat human skin disorders. In this review, we systematically evaluate current data regarding microbial ecology of healthy skin and gut, diet, pre- and probiotics, and antibiotics, on gut microbiome and their effects on skin health. We discuss potential mechanisms of the gut-skin axis and the link between the gut and skin-associated diseases, such as psoriasis, atopic dermatitis, acne vulgaris, rosacea, alopecia areata, and hidradenitis suppurativa. This review will increase our understanding of the impacts of gut microbiome on skin conditions to aid in finding new medications for skin-associated diseases.

Impact of gut microbiome on skin health: gut-skin axis observed through the lenses of therapeutics and skin diseases

Purpose Limited studies have shown positive and negative associations of serum amylase A1 (SAA1) gene in childhood obesity, previously showed the relation with obesity in different ethnicity. The current study therefore investigated the impact of single nucleotide polymorphisms present in the SAA1 gene on subjects of Saudi obesity. Participants and methods In this case-control study, we selected 140 subjects of Saudi population and categorized them into 83 cases of obesity and 57 healthy controls. Genotyping was performed with quantitative/real time-polymerase chain reaction in the SAA1 gene for rs11603089A/G, rs4638289A/T and rs7131332A/G polymorphisms. Results In rs11603089 polymorphism, co-dominant model (AG vs AA+GG; OR-2.23 [95% CI:1.02-4.86]; p=0.04) and rs4638289 polymorphism, a disparity in significance was observed between the homozygous variant (TT vs AA; OR-16.8 [95% CI: 2.06-136.8]; p=0.0009), dominant model (AT+TT vs AA; OR-2.57 [95% CI: 1.28-5.19]; p=0.007), recessive model (TT vs AA+AT; OR-11.36 [95% CI: 1.45-89.06]; p=0.004) and allelic frequency for (T vs A: OR-2.35 [95% CI: 1.39-3.98]; p=0.001) between the obesity cases and control subjects. However, statistical correlations did not reveal the rs7131332A/G polymorphism either (p>0.05). Conclusion In conclusion, rs4638289 polymorphism was associated with risk allele and dominant model with obesity subjects. Further additional studies were warranted.

Relationship Between Serum Amyloid A1 (SAA1) Gene Polymorphisms Studies with Obesity in the Saudi Population.

Meconium constitutes infants' first bowel movements postnatally. The consistency and microbial load of meconium are different from infant and adult stool. While recent evidence suggests that meconium is sterile in utero, rapid colonization occurs after birth. The meconium microbiome has been associated with negative health outcomes, but its composition is not well described, especially in preterm infants. Here, we characterized the meconium microbiomes from 330 very preterm infants (gestational ages 28 to 32 weeks) from 15 hospitals in Germany and in fecal samples from a subset of their mothers (N = 217). Microbiome profiles were compiled using 16S rRNA gene sequencing with negative and positive controls. The meconium microbiome was dominated by Bifidobacterium, Staphylococcus, and Enterococcus spp. and was associated with gestational age at birth and age at sample collection. Bifidobacterial abundance was negatively correlated with potentially pathogenic genera. The amount of bacterial DNA in meconium samples varied greatly across samples and was associated with the time since birth but not with gestational age or hospital site. In samples with low bacterial load, human mitochondrial sequences were highly amplified using commonly used, bacterial-targeted 16S rRNA primers. Only half of the meconium samples contained sufficient bacterial material to study the microbiome using a standard approach. To facilitate future meconium studies, we present a five-level scoring system ("MecBac") that predicts the success of 16S rRNA bacterial sequencing for meconium samples. These findings provide a foundational characterization of an understudied portion of the human microbiome and will aid the design of future meconium microbiome studies. IMPORTANCE Meconium is present in the intestines of infants before and after birth and constitutes their first bowel movements postnatally. The consistency, composition and microbial load of meconium is largely different from infant and adult stool. While recent evidence suggests that meconium is sterile in utero, rapid colonization occurs after birth. The meconium microbiome has been associated with short-term and long-term negative health outcomes, but its composition is not yet well described, especially in preterm infants. We provide a characterization of the microbiome structure and composition of infant meconium and maternal feces from a large study cohort and propose a method to evaluate meconium samples for bacterial sequencing suitability. These findings provide a foundational characterization of an understudied portion of the human microbiome and will aid the design of future meconium microbiome studies. 

Meconium Microbiome of Very Preterm Infants across Germany

Objective Fetal growth restriction (FGR) is a devastating pregnancy complication that increases the risk of perinatal mortality and morbidity. This study aims to determine the combined and relative effects of genetic and intrauterine environments on neonatal microbial communities and to explore selective FGR-induced gut microbiota disruption, metabolic profile disturbances and possible outcomes. Design We profiled and compared the gut microbial colonisation of 150 pairs of twin neonates who were classified into four groups based on their chorionicity and discordance of fetal birth weight. Gut microbiota dysbiosis and faecal metabolic alterations were determined by 16S ribosomal RNA and metagenomic sequencing and metabolomics, and the long-term effects were explored by surveys of physical and neurocognitive development conducted after 2~3 years of follow-up. Results Adverse intrauterine environmental factors related to selective FGR dominate genetics in their effects of elevating bacterial diversity and altering the composition of early-life gut microbiota, and this effect is positively related to the severity of selective FGR in twins. The influence of genetic factors on gut microbes diminishes in the context of selective FGR. Gut microbiota dysbiosis in twin neonates with selective FGR and faecal metabolic alterations features decreased abundances of Enterococcus and Acinetobacter and downregulated methionine and cysteine levels. Correlation analysis indicates that the faecal cysteine level in early life is positively correlated with the physical and neurocognitive development of infants. Conclusion Dysbiotic microbiota profiles and pronounced metabolic alterations are associated with selective FGR affected by adverse intrauterine environments, emphasising the possible effects of dysbiosis on long-term neurobehavioural development.

/pdf/unfavourable-intrauterine-environment-contributes-to-coen3205.pdf

Unfavourable intrauterine environment contributes to abnormal gut microbiome and metabolome in twins

Selective intrauterine fetal growth restriction (sIUGR) in monochorionic diamniotic twins, especially types 2&3 with abnormal umbilical artery Doppler, results in increased risk of fetal/perinatal mortality and postnatal disability. We investigate whether the hair metabolome profiles of neonates were associated with the pathophysiological differences across the different clinical forms of sIUGR in twins. Hair samples were collected at delivery from 10 pairs of type 1 sIUGR twins, 8 pairs of types 2&3 sIUGR twins, and 11 pairs of twins without sIUGR. The hair metabolome was characterized using gas chromatography-mass spectrometry. Our results demonstrated that the hair metabolite profiles of the different sIUGR subclinical forms were associated with the averaged fetal growth rate after 28 weeks of gestation but not with birthweight. The hair profiles were capable of discriminating type2&3 sIUGR twins from twins without sIUGR. In particular, the metabolites 2-aminobutyric acid, cysteine, alanine, and tyrosine all displayed areas under the receiver operating characteristic curve were above 0.9. The metabolic pathway analysis highlighted the associations of sIUGR twins with abnormal umbilical artery flow with increased metabolites from a nutrient depletion pathway, glutathione metabolism, and nerve development. This study offers novel insight into the severity of intrauterine ischemia and hypoxia for T2&3 sIUGR twins, through evaluation of the neonatal hair metabolome.

/pdf/neonatal-hair-profiling-reveals-a-metabolic-phenotype-of-4l5n8ymdmb.pdf

Neonatal hair profiling reveals a metabolic phenotype of monochorionic twins with selective intrauterine growth restriction and abnormal umbilical artery flow.

The early-life microbiota triggers life-long effects on physiological functions and health disorders. Previous studies in adult twins or animal models have revealed associations between host genetics and the harmonious microbiota. However, such associations may be obscured by the fact that each intra-pair of twins will continually encounter various environmental factors as they grow up. Here, we collected the meconium samples from nineteen dizygotic pairs (DZ, n = 38) and nine monozygotic pairs (MZ, n = 18) with cesarean delivery, and 16S rRNA gene sequencing was performed to profile the microbiome at birth. Diversity analysis showed that alpha diversity was not significantly different between two groups, whereas beta diversity of MZ twins was significantly lower than that of either DZ twins or unrelated individuals (i.e., randomly selected individual pairs of non-twinship) (p < 0.05). Two groups had very similar microbial classifications but different relative abundances of certain taxa including more Firmicutes (p = 0.05, Wilcoxon test) at the phylum level and lower abundances of five genera (p < 0.05) in DZ group compared to MZ group, including Rheinheimera, Proteus, SMB53, Sphingobium, and Megamonas. Co-occurrence analysis in each group showed slightly more complicated microbial interactions in DZ than MZ twins, although 22 shared bacterial genera co-existed in two groups, with both Rheinheimera and Megamonas having different centralities in their respective co-occurrence networks. Mean intra-class correlation coefficient (ICC) were also significantly higher for MZ (0.312) compared to DZ twins (0.138) (p < 0.05). The predicted microbial gene functions related to carbohydrate were higher in DZ group, whereas folding, sorting, degradation, cell motility pathways and energy metabolism were markedly over-represented in the microbiota of MZ group. In summary, our study uncovered that microbial diversity and components of the meconium microbiome between DZ and MZ twins were partially consistent with that in singleton neonates by cesarean delivery, but several distinctions related to the heritability supported genetic contributions to intestinal microbiome in early life.

/pdf/comparison-of-meconium-microbiome-in-dizygotic-and-8bmonuqygn.pdf

Zailing Li

Papers

Neonatal hair profiling reveals a metabolic phenotype of monochorionic twins with selective intrauterine growth restriction and abnormal umbilical artery flow.

Comparison of Meconium Microbiome in Dizygotic and Monozygotic Twins Born by Caesarean Section (CS).