Inflammatory bowel diseases (IBD) are a group of complex and multifactorial disorders with unknown etiology. Chronic intestinal inflammation develops against resident intestinal bacteria in genetically susceptible hosts. We hypothesized that host intestinal immunoglobulin (Ig) G can be used to identify bacteria involved in IBD pathogenesis. IgG-bound and -unbound microorganisms were collected from 32 pediatric terminal ileum aspirate washes during colonoscopy [non-IBD (n = 10), Crohn disease (n = 15), and ulcerative colitis (n = 7)], and composition was assessed using the Illumina MiSeq platform. In vitro analysis of invasive capacity was evaluated by fluorescence in situ hybridization and gentamicin invasion assay; immune activation was measured by qPCR. Despite considerable inter-individual variations, IgG binding favored specific and unique mucosa-associated species in pediatric IBD patients. Burkholderia cepacia, Flavonifractor plautii, and Rumminococcus sp. demonstrated increased IgG binding, while Pseudomonas ST29 demonstrated reduced IgG binding, in IBD. In vitro validation confirmed that B. cepacia, F. plautii, and Rumminococcus display invasive potential while Pseudomonas protogens did not. Using IgG as a marker of pathobionts in larger patient cohorts to identify microbes and elucidate their role in IBD pathogenesis will potentially underpin new strategies to facilitate development of novel, targeted diagnostic, and therapeutic approaches. Interestingly, this method can be used beyond the scope of this manuscript to evaluate altered gut pathobionts in a number of diseases associated with altered microbiota including arthritis, obesity, diabetes mellitus, alcoholic liver disease, cirrhosis, metabolic syndrome, and carcinomas.

Global incidence rates for inflammatory bowel disease (IBD) have gradually risen over the past 20 years. Genome-wide association studies (GWAS) have identified over 160 genetic loci associated with IBD; however, inherited factors only account for a partial contribution to the disease risk. We have recently shown that urban airborne particulate matter (PM) ingested via contaminated food can alter gut microbiome and immune function under normal and inflammatory conditions. In this addendum, we will discuss how PM can modify the gut microbial form and function, provide evidence on changes seen in intestinal barrier, and suggest a working hypothesis of how pollutants affect the gastrointestinal tract. The significance of the work presented could lead to identifying airborne pollutants as potential risk factors and thus provide better patient care management.

Particulate matter (PM) is a key pollutant in ambient air that has been associated with negative health conditions in urban environments. The aim of this study was to examine the effects of orally administered PM on the gut microbiome and immune function under normal and inflammatory conditions. Wild-type 129/SvEv mice were gavaged with Ottawa urban PM₁₀ (EHC-93) for 7–14 days and mucosal gene expression analyzed using Ingenuity Pathways software. Intestinal permeability was measured by lactulose/mannitol excretion in urine. At sacrifice, segments of small and large intestine were cultured and cytokine secretion measured. Splenocytes were isolated and incubated with PM₁₀ for measurement of proliferation. Long-term effects of exposure (35 days) on intestinal cytokine expression were measured in wild-type and IL-10 deficient (IL-10^−/−) mice. Microbial composition of stool samples was assessed using terminal restriction fragment length polymorphism. Short chain fatty acids were measured in caecum. Short-term treatment of wild-type mice with PM₁₀ altered immune gene expression, enhanced pro-inflammatory cytokine secretion in the small intestine, increased gut permeability, and induced hyporesponsiveness in splenocytes. Long-term treatment of wild-type and IL-10^−/− mice increased pro-inflammatory cytokine expression in the colon and altered short chain fatty acid concentrations and microbial composition. IL-10^−/− mice had increased disease as evidenced by enhanced histological damage. Ingestion of airborne particulate matter alters the gut microbiome and induces acute and chronic inflammatory responses in the intestine.

The intestinal epithelium must discriminate between pathogenic and nonpathogenic bacteria and respond accordingly. The aim of this study was to examine whether bacterial DNA can serve as the molecular basis for bacterial recognition. HT-29 monolayers were treated with various bacterial DNA and interleukin (IL)-8 secretion measured by enzyme-linked immunosorbent assay, nuclear factor κB activation by electrophoretic mobility shift assay and reporter assays, and IκB levels by Western blotting. Cytokine secretion in response to bacterial DNA was measured in murine colonic segments and splenocytes. IL-10–deficient mice were fed DNA from VSL probiotic compound daily for 2 weeks. Colons were removed and analyzed for cytokine production and inflammation. HT-29 cells responded with IL-8 secretion to bacterial DNA in a differential manner. In the presence of proinflammatory stimuli, VSL3 DNA inhibited IL-8 secretion, reduced p38 mitogen-activated protein kinase activation, delayed nuclear factor κB activation, stabilized levels of IκB, and inhibited proteasome function. VSL3 DNA inhibited colonic interferon (IFN)-γ secretion in mouse colons and also attenuated a Bacteroides vulgatus–induced IFN-γ release from murine splenocytes. In mice, VSL3 DNA attenuated a systemic release of tumor necrosis factor α in response to Escherichia coli DNA injection. Treatment of IL-10–deficient mice with oral VSL3 DNA resulted in a reduction in mucosal secretion of tumor necrosis factor α and IFN-γ and an improvement in histologic disease. DNA from probiotic bacteria can limit epithelial proinflammatory responses in vivo and in vitro. Systemic and oral administration of VSL3 DNA ameliorates inflammatory responses.