Title: 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 dysbiotic conditions, 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 the metaproteomes measured in five Crohn’s-diseased patients’ post-resection surgery across five time points over the course of one year, in order to examine persistence of microbial taxa, genes, proteins,more » and metabolic functional distributions across time in individuals whose microbiome might be highly 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 phylabut 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.« less

Authors:

Blakeley-Ruiz, J. Alfredo ^[1]; Erickson, Alison R. ^[2]; Cantarel, Brandi L. ^[3]; Xiong, Weili ^[4]; Adams, Rachel ^[5]; Jansson, Janet K. ^[6]; Fraser, Claire M. ^[7]; Hettich, Robert L.  ^[1]

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+ Show Author Affiliations

1. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Univ. of Tennessee, Knoxville, TN (United States)
2. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Harvard Medical School, Boston, MA (United States)
3. Univ. of Maryland School of Medicine, Baltimore, MD (United States); UT Southwestern Medical Center, Dallas, TX (United States)
4. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); U.S. Food and Drug Administration, College Park, MD (United States)
5. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
6. Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
7. Univ. of Maryland School of Medicine, Baltimore, MD (United States)

Publication Date:

2019-02-11

Research Org.:

Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

Sponsoring Org.:

USDOE

OSTI Identifier:

1495989

Alternate Identifier(s):

OSTI ID: 1507756

Report Number(s):

PNNL-SA-139569
Journal ID: ISSN 2049-2618

Grant/Contract Number:  

AC05-00OR22725; AC05-76RL01830

Resource Type:

Accepted Manuscript

Journal Name:

Microbiome

Additional Journal Information:

Journal Volume: 7; Journal Issue: 1; Journal ID: ISSN 2049-2618

Publisher:

BioMed Central

Country of Publication:

United States

Language:

English

Subject:

59 BASIC BIOLOGICAL SCIENCES; Gut microbiome; Metaproteomics; Crohn’s disease; Longitudinal analyses; Microbial metabolic function; Human microbiome