Objective To characterize the ecological effects of biologic therapies on the gut bacterial and fungal microbiome in psoriatic arthritis (PsA)/spondyloarthritis (SpA) patients. Methods Fecal samples from PsA/SpA patients pre‐ and posttreatment with tumor necrosis factor inhibitors (TNFi; n = 15) or an anti–interleukin‐17A monoclonal antibody inhibitor (IL‐17i; n = 14) underwent sequencing (16S ribosomal RNA, internal transcribed spacer and shotgun metagenomics) and computational microbiome analysis. Fecal levels of fatty acid metabolites and cytokines/proteins implicated in PsA/SpA pathogenesis or intestinal inflammation were correlated with sequence data. Additionally, ileal biopsies obtained from SpA patients who developed clinically overt Crohn's disease (CD) after treatment with IL‐17i (n = 5) were analyzed for expression of IL‐23/Th17–related cytokines, IL‐25/IL‐17E–producing cells, and type 2 innate lymphoid cells (ILC2s). Results There were significant shifts in abundance of specific taxa after treatment with IL‐17i compared to TNFi, particularly Clostridiales (P = 0.016) and Candida albicans (P = 0.041). These subclinical alterations correlated with changes in bacterial community co‐occurrence, metabolic pathways, IL‐23/Th17–related cytokines, and various fatty acids. Ileal biopsies showed that clinically overt CD was associated with expansion of IL‐25/IL‐17E–producing tuft cells and ILC2s (P < 0.05), compared to pre–IL‐17i treatment levels. Conclusion In a subgroup of SpA patients, the initiation of IL‐17A blockade correlated with features of subclinical gut inflammation and intestinal dysbiosis of certain bacterial and fungal taxa, most notably C albicans. Further, IL‐17i–related CD was associated with overexpression of IL‐25/IL‐17E–producing tuft cells and ILC2s. These results may help to explain the potential link between inhibition of a specific IL‐17 pathway and the (sub)clinical gut inflammation observed in SpA.

Background: Growing up on traditional, single-family farms is associated with protection against asthma in school age, but the mechanisms against early manifestations of atopic disease are largely unknown. We sought determine the gut microbiome and metabolome composition in rural Old Order Mennonite (OOM) infants at low risk and Rochester, NY urban/suburban infants at high risk for atopic diseases. Methods: In a cohort of 65 OOM and 39 Rochester mother-infant pairs, 101 infant stool and 61 human milk samples were assessed by 16S rRNA gene sequencing for microbiome composition and qPCR to quantify Bifidobacterium spp. and B. longum ssp. infantis (B. infantis), a consumer of human milk oligosaccharides (HMOs). Fatty acids (FAs) were analyzed in 34 stool and human 24 milk samples. Diagnoses and symptoms of atopic diseases by 3 years of age were assessed by telephone.

Background The gut microbiome plays an important role in autoimmunity including multiple sclerosis and its mouse model called experimental autoimmune encephalomyelitis (EAE). Prior studies have demonstrated that the multiple sclerosis gut microbiota can contribute to disease, hence making it a potential therapeutic target. In addition, antibiotic treatment has been shown to ameliorate disease in the EAE mouse model of multiple sclerosis. Yet, to this date, the mechanisms mediating these antibiotic effects are not understood. Furthermore, there is no consensus on the gut-derived bacterial strains that drive neuroinflammation in multiple sclerosis. Results Here, we characterized the gut microbiome of untreated and vancomycin-treated EAE mice over time to identify bacteria with neuroimmunomodulatory potential. We observed alterations in the gut microbiota composition following EAE induction. We found that vancomycin treatment ameliorates EAE, and that this protective effect is mediated via the microbiota. Notably, we observed increased abundance of bacteria known to be strong inducers of regulatory T cells, including members of Clostridium clusters XIVa and XVIII in vancomycin-treated mice during the presymptomatic phase of EAE, as well as at disease peak. We identified 50 bacterial taxa that correlate with EAE severity. Interestingly, several of these taxa exist in the human gut, and some of them have been implicated in multiple sclerosis including Anaerotruncus colihominis, a butyrate producer, which had a positive correlation with disease severity. We found that Anaerotruncus colihominis ameliorates EAE, and this is associated with induction of RORγt+ regulatory T cells in the mesenteric lymph nodes. Conclusions We identified vancomycin as a potent modulator of the gut-brain axis by promoting the proliferation of bacterial species that induce regulatory T cells. In addition, our findings reveal 50 gut commensals as regulator of the gut-brain axis that can be used to further characterize pathogenic and beneficial host-microbiota interactions in multiple sclerosis patients. Our findings suggest that elevated Anaerotruncus colihominis in multiple sclerosis patients may represent a protective mechanism associated with recovery from the disease.

BackgroundIn addition to farming exposures in childhood, maternal farming exposures provide strong protection against allergic disease in their children; however, the effect of farming lifestyle on human milk (HM) composition is unknown.ObjectiveThis study aims to characterize the maternal immune effects of Old Order Mennonite (OOM) traditional farming lifestyle when compared with Rochester (ROC) families at higher risk for asthma and allergic diseases using HM as a proxy.MethodsHM samples collected at median 2 months of lactation from 52 OOM and 29 ROC mothers were assayed for IgA1 and IgA2 antibodies, cytokines, endotoxin, HM oligosaccharides (HMOs), and targeted fatty acid (FA) metabolites. Development of early childhood atopic diseases in children by 3 years of age was assessed. In addition to group comparisons, systems level network analysis was performed to identify communities of multiple HM factors in ROC and OOM lifestyle.ResultsHM contains IgA1 and IgA2 antibodies broadly recognizing food, inhalant, and bacterial antigens. OOM HM has significantly higher levels of IgA to peanut, ovalbumin, dust mites, and Streptococcus equii as well TGF-β2, and IFN-λ3. A strong correlation occurred between maternal antibiotic use and levels of several HMOs. Path-based analysis of HMOs shows lower activity in the path involving lactoneohexaose (LNH) in the OOM as well as higher levels of lacto-N-neotetraose (LNnT) and two long-chain FAs C-18OH (stearic acid) and C-23OH (tricosanoic acid) compared with Rochester HM. OOM and Rochester milk formed five different clusters, e.g., butyrate production was associated with Prevotellaceae, Veillonellaceae, and Micrococcaceae cluster. Development of atopic disease in early childhood was more common in Rochester and associated with lower levels of total IgA, IgA2 to dust mite, as well as of TSLP.ConclusionTraditional, agrarian lifestyle, and antibiotic use are strong regulators of maternally derived immune and metabolic factors, which may have downstream implications for postnatal developmental programming of infant’s gut microbiome and immune system.

Understanding how viral infections impact and are modulated by the microbiome is an important problem in basic research but is also of high clinical relevance under the current pandemic. To facilitate the study of interactions between microbial communities and pathogenic viruses under safe conditions, the infectious agent is generally inactivated prior to processing samples.

Although high-throughput data allow researchers to interrogate thousands of variables simultaneously, it can also introduce a significant number of spurious results. Here we demonstrate that correlation analysis of large datasets can yield numerous false positives due to the presence of outliers that canonical methods fail to identify. We present Correlations Under The InfluencE (CUTIE), an open-source jackknifing-based method to detect such cases with both parametric and non-parametric correlation measures, and which can also uniquely rescue correlations not originally deemed significant or with incorrect sign. Our approach can additionally be used to identify variables or samples that induce these false correlations in high proportion. A meta-analysis of various omics datasets using CUTIE reveals that this issue is pervasive across different domains, although microbiome data are particularly susceptible to it. Although the significance of a correlation eventually depends on the thresholds used, our approach provides an efficient way to automatically identify those that warrant closer examination in very large datasets.

There are at least six variants of junctional epidermolysis bullosa (JEB). About 20 cases of the generalized atrophic benign variant of JEB (GABEB) have been previously reported. We present an additional case of GABEB, occurring in a 14-year-old girl. Generalized cutaneous blisters occurred since birth and healed without severe scarring or milia, but with slight atrophy. In addition, mucous membrane involvement and hair, nail and tooth abnormalities were found. Electron microscopic examination showed a cleavage within the lamina lucida and the presence of numerically and structurally abnormal hemidesmosomes.

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