Graphical Abstract Highlights d Bacteriophages target specific bacteria and mitigate bacterially driven colon cancer d Phages activate phage-specific and non-specific IFN-g mediated immune responses via TLR9 d Phages exacerbate colitis, and TLR9/IFNg blockade abrogates phage-mediated inflammation d UC patient responses to fecal microbiota therapy correlate with Caurovirales abundance SUMMARY Bacteriophages are the most abundant members of the microbiota and have the potential to shape gut bacterial communities. Changes to bacteriophage composition are associated with disease, but how phages impact mammalian health remains unclear. We noted an induction of host immunity when experimentally treating bacterially driven cancer, leading us to test whether bacteriophages alter immune responses. Treating germ-free mice with bacteriophages leads to immune cell expansion in the gut. Lactobacillus, Escherichia, and Bacteroides bacteriophages and phage DNA stimulated IFN-g via the nucleotide-sensing receptor TLR9. The resultant immune responses were both phage and bacteria specific. Additionally, increasing bacteriophage levels exacerbated colitis via TLR9 and IFN-g. Similarly, ulcerative colitis (UC) patients responsive to fecal microbiota transplantation (FMT) have reduced phages compared to non-responders, and mucosal IFN-g positively correlates with bacteriophage levels. Bacteriophages from active UC patients induced more IFN-g compared to healthy individuals. Collectively, these results indicate that bacteriophages can alter mucosal immunity to impact mammalian health. Duerkop, B.A., and Hooper, L.V. (2013). Resident viruses and their interactions with the immune system. Nat. Immunol. 14, 654-659.

Peripheral spondyloarthritis (SpA) is a common extra-intestinal manifestation in patients with active inflammatory bowel disease (IBD) characterized by inflammatory enthesitis, dactylitis, or synovitis of non-axial joints. However, a mechanistic understanding of the link between intestinal inflammation and SpA has yet to emerge. Here, we evaluated and functionally characterized the fecal microbiome of IBD patients with or without peripheral SpA. Coupling the sorting of IgA-coated microbiota with 16S rRNA-based analysis (IgA-seq) revealed a selective enrichment in IgA-coated E. coli in patients with Crohn’s disease-associated SpA (CD-SpA) compared to CD alone. E. coli isolates from CD-SpA-derived IgA-coated bacteria were similar in genotype and phenotype to an Adherent-invasive E. coli (AIEC) pathotype. In comparison to non-AIEC E. coli, colonization of germ-free mice with CD-SpA E. coli isolates induced Th17 mucosal immunity, which required the virulence-associated metabolic enzyme propanediol dehydratase (pduC). Modeling the increase in mucosal and systemic Th17 immunity we observed in CD-SpA patients, colonization of IL-10 deficient or K/BxN mice with CD-SpA-derived E. coli lead to more severe colitis or inflammatory arthritis, respectively. Collectively, these data reveal the power of IgA-seq to identify immune-reactive resident pathosymbionts that link mucosal and systemic Th17-dependent inflammation and offer microbial and immunophenotype stratification of CD-SpA that may guide medical and biologic therapy.

N ew York City is the epicenter of the US coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with local population infection rates estimated at 25%. 1 The impact of COVID-19 on patients with inflammatory bowel disease (IBD) within an epicenter is not well understood. Our study aims were to compare clinical outcomes between COVID-19 patients with and without IBD and to investigate the prevalence and risk factors of COVID-19 in IBD patients.

Background: Recent trials suggest fecal microbiota transplantation (FMT) with repeated enemas and high diversity FMT donors is a promising treatment to induce remission in ulcerative colitis (UC). Methods: We designed a prospective, open-label pilot study to assess the safety, clinical efficacy, and microbial engraftment of single FMT delivery by colonoscopy for active UC using a two donor fecal microbiota preparation (FMP). Safety and clinical endpoints of response, remission, and mucosal healing at week 4 were assessed. Fecal DNA and rectal biopsies were used to characterize the microbiome and mucosal CD4+ T cells, respectively, before and after FMT. Results: Seven patients (35%) achieved a clinical response by week 4. Three patients (15%) were in remission at week 4 and two of these patients (10%) achieved mucosal healing. Three patients (15%) required escalation of care. No serious adverse events were observed. Microbiome analysis revealed that restricted diversity of recipients pre-FMT was significantly increased by high diversity two donor FMP. The microbiome of recipients post-transplant was more similar to the donor FMP than the pre-transplant recipient sample in both responders and non-responders. Notably, donor composition correlated with clinical response. Mucosal CD4+ T cell analysis revealed a reduction in both Th1 and regulatory T cells post-FMT. Conclusions: High-diversity, two donor FMP delivery by colonoscopy is safe and effective in increasing fecal microbial diversity in patients with active UC. Donor composition correlated with clinical response and further characterization of immunological parameters may provide insight into factors influencing clinical outcome.

In patients with IBD, participation in the BBMW was associated with significant improvements in psychological and physical symptoms, quality of life, and C-reactive protein. Mind-body interventions, such as BBMW, which emphasize Voluntarily Regulated Breathing Practices, may have significant long-lasting benefits for IBD symptoms, anxiety, depression, quality of life, and inflammation. BBMW, a promising adjunctive treatment for IBD, warrants further study.

Early detection and treatment of malnutrition in patients on hemodialysis (HD) is hampered by lack of a sensitive biochemical marker. We compared the value of serum insulin-like growth factor-I (IGF-I) with other biochemical indices in detecting malnutrition in 61 HD patients. Protein and energy intakes were low in the majority of patients. Of all patients, 59.6% had severe reduction in triceps skinfold thickness (TSF thickness, less than or equal to 60% of normal), whereas midarm muscle circumference (MAMC) was mildly reduced (less than or equal to 90%) in 23%. Serum IGF-I proved superior to the other indices in predicting TSF thickness. A serum IGF-I concentration of 300 micrograms/L discriminated between wasted (TSF thickness less than or equal to 60%) and robust patients. In 16 patients with a history of recent infection, IGF-I was significantly reduced well before changes in anthropometric measurements could be detected. IGF-I is a useful and early marker of undernutrition in HD patients.

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Undernutrition in dialysis patients contributes to their morbidity and mortality. This is a cross-sectional study of the nutritional status of 61 patients treated with continuous ambulatory peritoneal dialysis (CAPD). They were studied with emphasis on assessment of their nutritional intake, anthropometric measurements, and evaluation of biochemical parameters. The correlation between the rate of CAPD peritonitis and these measurements was also examined. The majority of the patients (63.1%) had inadequate protein intake ( ≤ 1.2 g/kg/day). A comparable percentage had a low energy intake (≤ 30 kcal/ kg/day). Moderate malnutrition, as assessed by a low triceps skinfold thickness (TST) or a reduced midarm muscle circumference (MAMC) of ≤ 20th percentile, was detected in 52% and 39% of the patients, respectively. Severe malnutrition (TST or MAMC ≤ 10th percentile) was present in 36% of the patients. The serum insulin-like growth factor I (IGF-I) proved to be the most useful biochemical marker of malnutrition. It showed a positive correlation with TST (r = 0.325; p < 0.05). No significant correlation was observed with other short-life proteins such a transferrin or prealbumin. However, stepwise regression analysis showed the predictive value of serum IGF-I for anthropometric values to be low (adjusted R² = 34.6%). Wasted patients did not appear to have more infections when compared to their healthier counterparts. However, a weak correlation was observed between TST and the number of peritonitis episodes. In conclusion, we have confirmed the high prevalence of malnutrition in our population of CAPD patients, identified a low intake of nutrients as a contributing factor, and examined the value of serum IGF-I as a marker of the nutritional status.