Diet-omics in the Study of Urban and Rural Crohn disease Evolution (SOURCE) cohort

Braun, Tzipi; Feng, Rui; Amir, Amnon; Levhar, Nina; Shacham, Hila; Mao, Ren; Hadar, Rotem; Toren, Itamar; Algavi, Yadid; Abu-Saad, Kathleen; Zhuo, Shuoyu; Efroni, Gilat; Malik, Alona; Picard, Orit; Yavzori, Miri; Agranovich, Bella; Liu, Ta-Chiang; Stappenbeck, Thaddeus S.; Denson, Lee; Kalter-Leibovici, Ofra; Gottlieb, Eyal; Borenstein, Elhanan; Elinav, Eran; Chen, Minhu; Ben-Horin, Shomron; Haberman, Yael

doi:10.1038/s41467-024-48106-6

Cited by 4 publications

(2 citation statements)

References 66 publications

(71 reference statements)

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“…Notably, increased dietary Mn intake was recently identified as a protective against Crohn’s disease; while at the population-level, the intake of dietary Mn has decreased by >40% in the last 15 years. 74, 75 Regulation of de novo UDP-GlcNAc availability is dependent on the hexosamine biosynthetic pathway that integrates the metabolism of carbohydrates, amino acids, fat, and nucleotides, with supply also determined by salvage pathways. Supply of GlcNAc in the gut may also be determined by resident microbiota and degradation of dietary-derived monosaccharides and glycopeptides.…”

Section: Discussionmentioning

confidence: 99%

Aberrant N-glycosylation is a therapeutic target in carriers of a common and highly pleiotropic mutation in the manganese transporter ZIP8

Tomar,

Kang,

Lin

et al. 2024

Preprint

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The treatment of defective glycosylation in clinical practice has been limited to patients with rare and severe phenotypes associated with congenital disorders of glycosylation (CDG). Carried by approximately 5% of the human population, the discovery of the highly pleiotropic, missense mutation in a manganese transporter ZIP8 has exposed under-appreciated roles for Mn homeostasis and aberrant Mn-dependent glycosyltransferases activity leading to defective N-glycosylation in complex human diseases. Here, we test the hypothesis that aberrant N-glycosylation contributes to disease pathogenesis of ZIP8 A391T-associated Crohn’s disease. Analysis of N-glycan branching in intestinal biopsies demonstrates perturbation in active Crohn’s disease and a genotype-dependent effect characterized by increased truncated N-glycans. A mouse model of ZIP8 391-Thr recapitulates the intestinal glycophenotype of patients carrying mutations in ZIP8. Borrowing from therapeutic strategies employed in the treatment of patients with CDGs, oral monosaccharide therapy with N-acetylglucosamine ameliorates the epithelial N-glycan defect, bile acid dyshomeostasis, intestinal permeability, and susceptibility to chemical-induced colitis in a mouse model of ZIP8 391-Thr. Together, these data support ZIP8 391-Thr alters N-glycosylation to contribute to disease pathogenesis, challenging the clinical paradigm that CDGs are limited to patients with rare diseases. Critically, the defect in glycosylation can be targeted with monosaccharide supplementation, providing an opportunity for genotype-driven, personalized medicine.

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Section: Discussionmentioning

confidence: 99%

Aberrant N-glycosylation is a therapeutic target in carriers of a common and highly pleiotropic mutation in the manganese transporter ZIP8

Tomar,

Kang,

Lin

et al. 2024

Preprint

View full text Add to dashboard Cite

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“…Epidemiological and, more recently, dietary and multi-omics studies (i.e., Braun et al. 4 ) aim to capture the contribution of exposure to CD pathogenesis and the related gut microbial alterations. Many previous studies have shown alterations in the gut microbiome, but the specific bacteria involved have varied between studies.…”

Section: Main Textmentioning

confidence: 99%

All (remains) in the family? Using healthy relatives to define Crohn’s gut microbiome alterations

Amir,

Haberman

2024

Cell Reports Medicine

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Gut colonization ofEnterococcusspecies is associated with COVID-19 disease in Uganda

Agudelo,

Kateete,

Nasinghe

et al. 2024

Preprint

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Background: Infection with the COVID-19-causing pathogen SARS-CoV-2 is associated with disruption in the human gut microbiome. The gut microbiome enables protection against diverse pathogens and exhibits dysbiosis during infectious and autoimmune disease. Studies based in the United States and China have found that severe COVID-19 cases have altered gut microbiome composition when compared to mild COVID-19 cases. We present the first study to investigate the gut microbiome composition of COVID-19 cases in a population from Sub-Saharan Africa. Given the impact of geography and cultural traditions on microbiome composition, it is important to investigate the microbiome globally and not draw broad conclusions from homogenous populations. Results: We used stool samples in a Ugandan biobank collected from COVID-19 cases during 2020-2022. We profiled the gut microbiomes of 114 symptomatic individuals who tested positive for SARS-CoV-2 along with 76 household contacts who did not present any symptoms of COVID-19. The inclusion of healthy controls enables us to generate hypotheses about bacterial strains potentially related to susceptibility to COVID-19 disease, which is highly heterogeneous. Comparison of the COVID-19 patients and their household contacts revealed decreased alpha diversity and blooms of Enterococcus and Eggerthella in COVID-19 cases. Conclusions: Our study finds that the microbiome of COVID-19 individuals is more likely to be disrupted, as indicated by decreased diversity and increased pathobiont levels. This is either a consequence of the disease or may indicate that certain microbiome states increase susceptibility to COVID-19 disease. Our findings enable comparison with cohorts previously published in the Global North, as well as support new hypotheses about the interaction between the gut microbiome and SARS-CoV-2 infection.

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Diet-omics in the Study of Urban and Rural Crohn disease Evolution (SOURCE) cohort

Cited by 4 publications

References 66 publications

Aberrant N-glycosylation is a therapeutic target in carriers of a common and highly pleiotropic mutation in the manganese transporter ZIP8

Aberrant N-glycosylation is a therapeutic target in carriers of a common and highly pleiotropic mutation in the manganese transporter ZIP8

All (remains) in the family? Using healthy relatives to define Crohn’s gut microbiome alterations

Gut colonization ofEnterococcusspecies is associated with COVID-19 disease in Uganda

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