Dataset Information

Metaproteomics reveals persistent and phylum-redundant metabolic functional stability in adult human gut microbiomes of Crohn's remission patients despite temporal variations in microbial taxa, genomes, and proteomes.

ABSTRACT:

Background

The gut microbiome plays a fundamental role in the human host's overall health by contributing key biological functions such as expanded metabolism and pathogen defense/immune control. In a healthy individual, the gut microbiome co-exists within the human host in a symbiotic, non-inflammatory relationship that enables mutual benefits, such as microbial degradation of indigestible food products into small molecules that the host can utilize, and enhanced pathogen defense. In abnormal conditions, such as Crohn's disease, this favorable metabolic relationship breaks down and a variety of undesirable activities result, including chronic inflammation and other health-related issues. It has been difficult, however, to elucidate the overall functional characteristics of this relationship because the microbiota can vary substantially in composition for healthy humans and possibly even more in individuals with gut disease conditions such as Crohn's disease. Overall, this suggests that microbial membership composition may not be the best way to characterize a phenotype. Alternatively, it seems to be more informative to examine and characterize the functional composition of a gut microbiome. Towards that end, this study examines 25 metaproteomes measured in several Crohn's disease patients' post-resection surgery across the course of 1?year, in order to examine persistence of microbial taxa, genes, proteins, and metabolic functional distributions across time in individuals whose microbiome might be more variable due to the gut disease condition.

Results

The measured metaproteomes were highly personalized, with all the temporally-related metaproteomes clustering most closely by individual. In general, the metaproteomes were remarkably distinct between individuals and to a lesser extent within individuals. This prompted a need to characterize the metaproteome at a higher functional level, which was achieved by annotating identified protein groups with KEGG orthologous groups to infer metabolic modules. At this level, similar and redundant metabolic functions across multiple phyla were observed across time and between individuals. Tracking through these various metabolic modules revealed a clear path from carbohydrate, lipid, and amino acid degradation to central metabolism and finally the production of fermentation products.

Conclusions

The human gut metaproteome can vary quite substantially across time and individuals. However, despite substantial intra-individual variation in the metaproteomes, there is a clear persistence of conserved metabolic functions across time and individuals. Additionally, the persistence of these core functions is redundant across multiple phyla but is not always observable in the same sample. Finally, the gut microbiome's metabolism is not driven by a set of discrete linear pathways but a web of interconnected reactions facilitated by a network of enzymes that connect multiple molecules across multiple pathways.

SUBMITTER: Blakeley-Ruiz JA

PROVIDER: S-EPMC6371617 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Publications

Metaproteomics reveals persistent and phylum-redundant metabolic functional stability in adult human gut microbiomes of Crohn's remission patients despite temporal variations in microbial taxa, genomes, and proteomes.

Blakeley-Ruiz J Alfredo JA Erickson Alison R AR Cantarel Brandi L BL Xiong Weili W Adams Rachel R Jansson Janet K JK Fraser Claire M CM Hettich Robert L RL

Microbiome 20190211 1

<h4>Background</h4>The gut microbiome plays a fundamental role in the human host's overall health by contributing key biological functions such as expanded metabolism and pathogen defense/immune control. In a healthy individual, the gut microbiome co-exists within the human host in a symbiotic, non-inflammatory relationship that enables mutual benefits, such as microbial degradation of indigestible food products into small molecules that the host can utilize, and enhanced pathogen defense. In ab ...[more]

PMID: 30744677

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Project description:A critical step in studies of the intestinal microbiome using meta-omics approaches is the preservation of samples before analysis. Preservation is essential for approaches that measure gene expression, such as metaproteomics, which is used to identify and quantify proteins in microbiomes. Intestinal microbiome samples are typically stored by flash-freezing and storage at -80°C, but some experimental setups do not allow for immediate freezing of samples. In this study, we evaluated methods to preserve fecal microbiome samples for metaproteomics analyses when flash-freezing is not possible. We collected fecal samples from C57BL/6 mice and stored them for 1 and 4 weeks using the following methods: flash-freezing in liquid nitrogen, immersion in RNAlater, immersion in 95% ethanol, immersion in a RNAlater-like buffer, and combinations of these methods. After storage, we extracted protein and prepared peptides for liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis to identify and quantify peptides and proteins. All samples produced highly similar metaproteomes, except for ethanol-preserved samples that were distinct from all other samples in terms of protein identifications and protein abundance profiles. Flash-freezing and RNAlater (or RNAlater-like treatments) produced metaproteomes that differed only slightly, with less than 0.7% of identified proteins differing in abundance. In contrast, ethanol preservation resulted in an average of 9.5% of the identified proteins differing in abundance between ethanol and the other treatments. Our results suggest that preservation at room temperature in RNAlater or an RNAlater-like solution performs as well as freezing for the preservation of intestinal microbiome samples before metaproteomics analyses. IMPORTANCE Metaproteomics is a powerful tool to study the intestinal microbiome. By identifying and quantifying a large number of microbial, dietary, and host proteins in microbiome samples, metaproteomics provides direct evidence of the activities and functions of microbial community members. A critical step for metaproteomics workflows is preserving samples before analysis because protein profiles are susceptible to fast changes in response to changes in environmental conditions (air exposure, temperature changes, etc.). This study evaluated the effects of different preservation treatments on the metaproteomes of intestinal microbiome samples. In contrast to prior work on preservation of fecal samples for metaproteomics analyses, we ensured that all steps of sample preservation were identical so that all differences could be attributed to the preservation method.

Project description:BackgroundCrohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract, in which the pathogenesis is believed to be partly influenced by the gut microbiome. Probiotics can be used to manipulate the microbiome and have therefore been considered as a potential therapy for CD. There is some evidence that probiotics benefit other gastrointestinal conditions, such as irritable bowel syndrome and ulcerative colitis, but their efficacy in CD is unclear. This is the first update of a Cochrane Review previously published in 2008.ObjectivesTo assess the efficacy and safety of probiotics for the induction of remission in CD.Search methodsThe following electronic databases were searched: MEDLINE (from inception to 6 July 2020), Embase (from inception to 6 July 2020), the Cochrane Central Register of Controlled Trials (CENTRAL), The Cochrane IBD Review Group Specialised Trials Register, World Health Organization (WHO) International Clinical Trials Registry, and ClinicalTrials.gov.Selection criteriaRandomised controlled trials (RCTs) that compared probiotics with placebo or any other non-probiotic intervention for the induction of remission in CD were eligible for inclusion.Data collection and analysisTwo review authors independently extracted data and assessed the methodological quality of included studies. The primary outcome was clinical remission. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for dichotomous outcomes.Main resultsThere were two studies that met criteria for inclusion. One study from Germany had 11 adult participants with mild-to-moderate CD, who were treated with a one-week course of corticosteroids and antibiotics (ciprofloxacin 500 mg twice daily and metronidazole 250 mg three times a day), followed by randomised assignment to Lactobacillus rhamnosus strain GG (two billion colony-forming units per day) or corn starch placebo. The other study from the United Kingdom (UK) had 35 adult participants with active CD (CDAI score of 150 to 450) randomised to receive a synbiotic treatment (comprised of freeze-dried Bifidobacterium longum and a commercial product) or placebo. The overall risk of bias was low in one study, whereas the other study had unclear risk of bias in relation to random sequence generation, allocation concealment, and blinding. There was no evidence of a difference between the use of probiotics and placebo for the induction of remission in CD (RR 1.06; 95% CI 0.65 to 1.71; 2 studies, 46 participants) after six months. There was no difference in adverse events between probiotics and placebo (RR 2.55; 95% CI 0.11 to 58.60; 2 studies, 46 participants). The evidence for both outcomes was of very low certainty due to risk of bias and imprecision.Authors' conclusionsThe available evidence is very uncertain about the efficacy or safety of probiotics, when compared with placebo, for induction of remission in Crohn's disease. There is a lack of well-designed RCTs in this area and further research is needed.

Dataset Information

Metaproteomics reveals persistent and phylum-redundant metabolic functional stability in adult human gut microbiomes of Crohn's remission patients despite temporal variations in microbial taxa, genomes, and proteomes.

Background

Results

Conclusions

Publications

Metaproteomics reveals persistent and phylum-redundant metabolic functional stability in adult human gut microbiomes of Crohn's remission patients despite temporal variations in microbial taxa, genomes, and proteomes.

Similar Datasets

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