Analysis and Interpretation of the Human Microbiome

Ashton, James J.; Beattie, R Mark; Ennis, Sarah; Cleary, David W.

doi:10.1097/mib.0000000000000809

Cited by 12 publications

(18 citation statements)

References 72 publications

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“…Clustering of model-processed abundance data generated a cluster with a disproportionate number of pre-FMT samples, suggesting distinct metabolic function compared to donor and post-FMT communities as has been reported (70, 86,87). This cluster had elevated Consistent with these results, Cronobacter was found to be strongly positively correlated with 22 Enterobacteriaceae and strongly negatively correlated with Bacteroides across the FMT dataset.…”

Section: Discussionsupporting

confidence: 79%

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Computational Modeling of the Gut Microbiota Predicts Metabolic Mechanisms of RecurrentClostridioides difficileInfection

Henson

2020

Preprint

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Approximately 30% of patients who have a Clostridioides difficile infection (CDI) will suffer at least one incident of reinfection. While the underlying causes of CDI recurrence are poorly understood, interactions between C. difficile and other commensal gut bacteria are thought to play an important role. In this study, an in silico metagenomics pipeline was used to process taxa abundance data from 225 CDI patient stool samples into sample-specific models of bacterial community metabolism. The predicted metabolite production capabilities of each community were shown to provide improved recurrence prediction compared to direct use of taxa abundance data.More specifically, clustered metabolite synthesis rates generated from post-diagnosis samples produced a high Enterobacteriaceae cluster with disproportionate numbers of recurrent samples and patients. This cluster was predicted to have significantly reduced capabilities for secondary bile acid synthesis but elevated capabilities for aromatic amino acid catabolism. When applied to 40 samples from fecal microbiota transplantation (FMT) patients and their donors, community modeling generated a high Enterobacteriaceae cluster with a disproportionate number of pre-FMT samples. This cluster also was predicted to exhibit reduced secondary bile acid synthesis and elevated aromatic amino acid catabolism. Because clustering of CDI and FMT samples did not identify statistical differences in C. difficile abundances, these model predictions support the hypothesis that Enterobacteriaceae may create a gut environment favorable for C. difficile spore germination and toxin synthesis. ImportanceClostridioides difficile is an opportunistic human pathogen responsible for acute and sometimes chronic infections of the colon. Elderly individuals who are immunocompromised, frequently hospitalized and recipients of antibiotics are particular susceptible to infection. Approximately 3 30% of treated patients will suffer at least one episode of reinfection, commonly termed recurrence.The objective of the current study was to utilize computational metabolic modeling to investigate the hypothesis that recurrent infections are related to the composition of the gut bacterial community within each patient. Our model predictions suggest that patients who have high compositions of the bacterial family Enterobacteriaceae during antibiotic treatment are more likely to develop recurrent infections due to a metabolically-disrupted gut environment. Successful treatment of recurrent patients with transplanted fecal matter is predicted to correct this metabolic disruption, suggesting that interactions between C. difficile and Enterobacteriaceae are worthy of additional study.

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Section: Discussionsupporting

confidence: 79%

“…The advent of metagenomic technologies such as 16S rRNA-encoding gene sequencing has yielded unprecedent insights into the composition of in vivo bacterial communities (20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

Computational Modeling of the Gut Microbiota Predicts Metabolic Mechanisms of RecurrentClostridioides difficileInfection

Henson

2020

Preprint

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“…According to a prediction of cancer incidence and mortality in Korea, GC accounts for a remarkable proportion of the overall cancer burden because it is the second most common type of cancer among Koreans 4 . Recent studies about the human microbiome demonstrate a surge in interest in the context of disease, particularly in gastrointestinal cancers 5 . It is a known fact that there are various types of bacteria in different body sites, which are colloquially referred to as normal flora.…”

Section: Introductionmentioning

confidence: 99%

“…It is a known fact that there are various types of bacteria in different body sites, which are colloquially referred to as normal flora. This microbiota has the potential to maintain human health by interacting with the human body and can be considered pathological for the development of certain diseases 5 .…”

Section: Introductionmentioning

confidence: 99%

Association between the relative abundance of gastric microbiota and the risk of gastric cancer: a case-control study

Gunathilake

Lee

Choi

et al. 2019

Sci Rep

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The human gut hosts a diverse community of bacteria referred to as the gut microbiome. We investigated the association between the relative abundance of gastric microbiota and gastric cancer (GC) risk in a Korean population. The study participants included 268 GC patients and 288 controls. DNA was extracted from gastric biopsies, and 16S rRNA gene analysis was performed. Unconditional logistic regression models were used to observe the associations. Of the participants, those who had the highest level (highest tertile) of relative Helicobacter pylori and Propionibacterium acnes abundances showed a significantly higher risk for GC after adjusting for potential confounding variables (odds ratio (OR) = 1.86, 95% confidence interval (CI) = 1.17–2.97, p for trend = 0.017 and OR = 4.77, 95% CI = 2.94–7.74, p for trend <0.001, respectively). Subjects who carried Prevotella copri had a significantly higher risk of GC than noncarriers (OR = 2.54, 95% CI = 1.42–4.55, p for trend = 0.002). There was a lower risk of GC in subjects carrying Lactococcus lactis than in noncarriers (OR = 0.21, 95% CI = 0.10–0.44, p for trend <0.001). H. pylori, P. acnes and P. copri are strong risk factors, whereas L. lactis is a protective factor, for GC development in Koreans. Further microbiome studies are warranted to verify the findings of the current study.

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“…Many studies have attempted to examine if the EEN efficacy is attributed to improved gut microbiota. (Quince et al, 2015;Ashton et al, 2016;MacLellan et al, 2017). However, as all elemental and non-elemental diets are similarly effective in inducing remission of active CD, they lead to vastly different changes of microbiome in the gut (Ashton et al, 2016;Ashton et al, 2019).…”

Section: Attenuation Of Mechano-transcription Process As a Novel Mechanism Underlying The Benefits Of Exclusive Enteral Nutrition In Crohmentioning

confidence: 99%

Targeting Mechano-Transcription Process as Therapeutic Intervention in Gastrointestinal Disorders

et al. 2021

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Mechano-transcription is a process whereby mechanical stress alters gene expression. The gastrointestinal (GI) tract is composed of a series of hollow organs, often encountered by transient or persistent mechanical stress. Recent studies have revealed that persistent mechanical stress is present in obstructive, functional, and inflammatory disorders and alters gene transcription in these conditions. Mechano-transcription of inflammatory molecules, pain mediators, pro-fibrotic and growth factors has been shown to play a key role in the development of motility dysfunction, visceral hypersensitivity, inflammation, and fibrosis in the gut. In particular, mechanical stress-induced cyclooxygenase-2 (COX-2) and certain pro-inflammatory mediators in gut smooth muscle cells are responsible for motility dysfunction and inflammatory process. Mechano-transcription of pain mediators such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) may lead to visceral hypersensitivity. Emerging evidence suggests that mechanical stress in the gut also leads to up-regulation of certain proliferative and pro-fibrotic mediators such as connective tissue growth factor (CTGF) and osteopontin (OPN), which may contribute to fibrostenotic Crohn’s disease. In this review, we will discuss the pathophysiological significance of mechanical stress-induced expression of pro-inflammatory molecules, pain mediators, pro-fibrotic and growth factors in obstructive, inflammatory, and functional bowel disorders. We will also evaluate potential therapeutic targets of mechano-transcription process for the management of these disorders.

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Analysis and Interpretation of the Human Microbiome

Cited by 12 publications

References 72 publications

Computational Modeling of the Gut Microbiota Predicts Metabolic Mechanisms of RecurrentClostridioides difficileInfection

Computational Modeling of the Gut Microbiota Predicts Metabolic Mechanisms of RecurrentClostridioides difficileInfection

Association between the relative abundance of gastric microbiota and the risk of gastric cancer: a case-control study

Targeting Mechano-Transcription Process as Therapeutic Intervention in Gastrointestinal Disorders

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