Integrated microbiota and metabolite profiles link Crohn’s disease to sulfur metabolism

Metwaly, Amira; Dunkel, Andreas; Waldschmitt, Nadine; Raj, Abilash Chakravarthy Durai; Lagkouvardos, Ilias; Corraliza, A M; Mayorgas, Aida; Martínez-Medina, Margarita; Reiter, Sinah; Schloter, Michael; Hofmann, Thomas; Allez, Matthieu; Panés, Julián; Salas, Azucena; Haller, Dirk

doi:10.1038/s41467-020-17956-1

Cited by 103 publications

(124 citation statements)

References 86 publications

(110 reference statements)

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“…In IECs, H 2 S is capable of inducing genotoxic damage, and elevated levels of H 2 S can impair OXPHOS by inhibiting complex IV of the electron transfer chain (Ijssennagger et al, 2016;Saint-Georges-Chaumet and Edeas, 2016). Indicating disease relevance, an integrated microbiota and metabolite profile analysis has recently linked Crohn's disease activity to bacterial sulfur metabolism (Metwaly et al, 2020). Moreover, in IBD, an adverse microbiota-host interaction has been reported for H 2 S, with increased abundance of sulfate-reducing bacteria (i.e., H 2 S-producers) on the microbial side and a decreased expression of mitochondrial proteins involved in hydrogen sulfide detoxification on the host side (Mottawea et al, 2016).…”

Section: Mitochondria As Metabolic Integrators Of Microbial Signalsmentioning

confidence: 99%

Mitochondrial Metabolism in the Intestinal Stem Cell Niche—Sensing and Signaling in Health and Disease

Urbauer

Rath

Haller

2021

Front. Cell Dev. Biol.

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Mitochondrial metabolism, dynamics, and stress responses in the intestinal stem cell niche play a pivotal role in regulating intestinal epithelial cell homeostasis, including self-renewal and differentiation. In addition, mitochondria are increasingly recognized for their involvement in sensing the metabolic environment and their capability of integrating host and microbial-derived signals. Gastrointestinal diseases such as inflammatory bowel diseases and colorectal cancer are characterized by alterations of intestinal stemness, the microbial milieu, and mitochondrial metabolism. Thus, mitochondrial function emerges at the interface of determining health and disease, and failure to adapt mitochondrial function to environmental cues potentially results in aberrant tissue responses. A mechanistic understanding of the underlying role of mitochondrial fitness in intestinal pathologies is still in its infancy, and therapies targeting mitochondrial (dys)function are currently lacking. This review discusses mitochondrial signaling and metabolism in intestinal stem cells and Paneth cells as critical junction translating host- and microbe-derived signals into epithelial responses. Consequently, we propose mitochondrial fitness as a hallmark for intestinal epithelial cell plasticity, determining the regenerative capacity of the epithelium.

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Section: Mitochondria As Metabolic Integrators Of Microbial Signalsmentioning

confidence: 99%

Mitochondrial Metabolism in the Intestinal Stem Cell Niche—Sensing and Signaling in Health and Disease

Urbauer

Rath

Haller

2021

Front. Cell Dev. Biol.

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“…Human campylobacteriosis patients have an increased abundance of genera Escherichia, Bacteroidetes, Phascolarctobacterium, and Streptococcus in stool [3]. Comparably, microbiota sequencing data from cross-sectional IBD patients showed that IBD is associated with dysbiosis characterizing by reduced gut bacterial diversity, together with increased genera Fusobacterium, Escherichia, Faecalibacterium, Roseburia, Ruminococcaceae, Peptostreptococcaceae, Christensenellaceae, and Collinsella [88]. The changes in the gut microbiota of IBD patients show an increase in facultative anaerobes, including Escherichia coli [89], and a decrease in obligately anaerobic [90].…”

Section: Microbiota and Campylobacteriosismentioning

confidence: 98%

“…The changes in the gut microbiota of IBD patients show an increase in facultative anaerobes, including Escherichia coli [89], and a decrease in obligately anaerobic [90]. IBD patients with active disease have increased gut Enterococcus, Fusobacterium, Haemophilus, Megasphaera, Campylobacter, while Roseburia, Christensenellaceae, Oscillibacter, and Odoribacter are enriched in the gut of IBD patients with inactive disease [88]. Although increasing evidence supports the role of microbiota promoting C. jejuni infection or other enteritis, additional studies are much needed.…”

Section: Microbiota and Campylobacteriosismentioning

confidence: 99%

“…CD patients have increased levels of conjugated and sulfated bile acids in the feces [102]. In a functional analysis with shotgun metagenomics data, sulfur metabolism is identified with an enrichment of sulfonate, methionine, cysteine and taurine transport systems in mice colonized with microbiota from active IBD patients [88]. These metabolic changes are consistent with the increased abundance of sulfate-reducing bacteria (e.g., Desulfovibrio, Clostridia, Bilophila, and Bacteroides fragilis), some of which use sulfate as a terminal electron acceptor for respiration and concomitantly produce hydrogen disulfide, a toxic metabolic byproduct [88].…”

Section: Microbial Metabolites and Campylobacteriosismentioning

confidence: 99%

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The Role of Immune Response and Microbiota on Campylobacteriosis

Fu¹,

Alenezi²,

Almansour³

et al. 2022

Campylobacter

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Million cases of campylobacteriosis and complications of post-Campylobacter jejuni infection occur every year around the world with huge life losses and economic burdens of billions of dollars. Few therapy options, such as antibiotics, are available to relieve severe cases of the enteritis. The slow progression on new intervention discovery and application is partially resulted from limited mechanistic understanding on campylobacteriosis pathogenesis. As a type of intestinal disorders, campylobacteriosis shares many common features with other intestinal diseases such as inflammatory bowel diseases (IBD) and Clostridium difficile infection. In pace with the advancement of the gastroenterology field, a large body of knowledge is accumulating on the factors influencing campylobacteriosis onset, development, and outcomes, including host immune response, intestinal microbiota, and its metabolites. In this chapter, we review the intestinal immune system, intestinal microbiome, and microbiome modulation of inflammation in the development of campylobacteriosis. The interplay between immunity, microbiota, and its metabolites may play essential roles on campylobacteriosis pathogenesis and the finding on the interaction may lead to new prevention and treatment options. The purpose of this chapter is to provide updated knowledge on the role of host–microbe interaction and the therapeutic potential on campylobacteriosis.

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“…To this point, the gut microbiome has been demonstrated in recent years to facilitate detection of disease [30][31][32][33][34]; classification of disease subtypes and progression stages [35][36][37]; prediction of clinical outcomes and treatment efficacy [38][39][40][41][42]; personalized nutrition by prediction of postprandial glycemic response [43][44][45];…”

Section: Introductionmentioning

confidence: 99%

Gut Microbiome Predicts Clinically Important Improvement in Patients with Rheumatoid Arthritis

Gupta

Cunningham

Bakshi

et al. 2021

Preprint

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BackgroundRapid advances in the past decade have shown that dysbiosis of the gut microbiome is a key hallmark of rheumatoid arthritis (RA). Yet, the relationship between gut microbiome and clinical improvement in RA disease activity remains unclear. In this study, we explored the gut microbiome of patients with RA to identify features that are associated with, as well as predictive of, minimum clinically important improvement (MCII) in disease activity.MethodsWhole metagenome shotgun sequencing was performed on 64 stool samples, which were collected from 32 patients with RA at two separate time-points. The Clinical Disease Activity Index (CDAI) of each patient was measured at both time-points to assess achievement of MCII; depending on this clinical status, patients were distinguished into two groups. Multiple linear regression models were used to identify microbial taxa and biochemical pathways associated with MCII while controlling for potentially confounding factors. Lastly, a deep-learning neural network was trained upon gut microbiome, clinical, and demographic data at baseline to classify patients according to MCII status, thereby enabling the prediction of whether a patient will achieve MCII at follow-up.ResultsWe determined that MCII status can explain a significant proportion of the overall compositional variance in the gut microbiome (R2 = 3.8%, P = 0.005, PERMANOVA). Additionally, by looking at patients’ baseline gut microbiome profiles, we observed significantly different microbiome traits between patients who eventually showed MCII and those who did not. Taxonomic features include alpha- and beta-diversity measures, as well as several microbial taxa, such as Coprococcus, Bilophila sp. 4_1_30, and Ruminococcus sp. Functional profiling identified thirteen biochemical pathways, most of which were involved in the biosynthesis of L-arginine and L-methionine, to be differentially abundant between the MCII patient groups. In addition to these observations at baseline, we found microbiome features that vary differently in fold-change (from baseline to follow-up) between the two patient groups. These results could suggest that, depending on the clinical course, gut microbiomes not only start at different ecological states, but also are on separate trajectories. Finally, the neural network proved to be highly effective in predicting which patient will achieve MCII (balanced accuracy = 90.0%), demonstrating potential clinical utility of gut microbiome profiles.ConclusionsOur findings confirm the presence of taxonomic and functional signatures of the gut microbiome associated with MCII in RA patients. Ultimately, the gut microbiome may aid in the development of non-invasive tools for predicting future prognosis in RA.Trial registrationN/A

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Integrated microbiota and metabolite profiles link Crohn’s disease to sulfur metabolism

Cited by 103 publications

References 86 publications

Mitochondrial Metabolism in the Intestinal Stem Cell Niche—Sensing and Signaling in Health and Disease

Mitochondrial Metabolism in the Intestinal Stem Cell Niche—Sensing and Signaling in Health and Disease

The Role of Immune Response and Microbiota on Campylobacteriosis

Gut Microbiome Predicts Clinically Important Improvement in Patients with Rheumatoid Arthritis

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