Characterising the gut microbiome in veterans with Gulf War Illness: a protocol for a longitudinal, prospective cohort study

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Introduction

Approximately 25%–35% of the 1991 Gulf War Veteran population report symptoms consistent with Gulf War Illness (GWI), a chronic, multi-symptom illness characterised by fatigue, pain, irritable bowel syndrome and problems with cognitive function. GWI is a disabling problem for Gulf War Veterans, and there remains a critical need to identify innovative, novel therapies.

Gut microbiota perturbation plays a key role in the symptomatology of other chronic multi-symptom illnesses, including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Given similarities between ME/CFS and GWI and the presence of gastrointestinal disorders in GWI patients, Veterans with GWI may also have gut abnormalities like those seen with ME/CFS. In this longitudinal cohort study, we are comparing the diversity (structure) and the metagenomes (function) of the gut microbiome between Gulf War Veterans with and without GWI. If we find differences in Veterans with GWI, the microbiome could be a target for therapeutic intervention to alleviate GWI symptoms.

Methods and analysis

Participants answer questions about diet, exercise and lifestyle factors. Participants also complete a questionnaire (based on the Kansas case definition of GWI) regarding their medical history and symptoms; we use this questionnaire to group participants into GWI versus healthy control cohorts. We plan to enrol 52 deployed Gulf War Veterans: 26 with GWI and 26 healthy controls. Participants provide stool and saliva samples weekly for an 8-week period for microbiome analyses. Participants also provide blood samples at the beginning and end of this period, which we will use to compare measures of inflammation markers between the groups.

Ethics and dissemination

The protocol was approved by the University of Wisconsin-Madison Health Sciences Institutional Review Board and the William S. Middleton Memorial Veterans Hospital Research and Development Committee. Results of this study will be submitted for publication in a peer-reviewed journal.

Related collections

Most cited references 23

Record: found
Abstract: found
Article: not found

Power and sample-size estimation for microbiome studies using pairwise distances and PERMANOVA.

Brendan J. Kelly, Robert Gross, Kyle Bittinger … (2015)

The variation in community composition between microbiome samples, termed beta diversity, can be measured by pairwise distance based on either presence-absence or quantitative species abundance data. PERMANOVA, a permutation-based extension of multivariate analysis of variance to a matrix of pairwise distances, partitions within-group and between-group distances to permit assessment of the effect of an exposure or intervention (grouping factor) upon the sampled microbiome. Within-group distance and exposure/intervention effect size must be accurately modeled to estimate statistical power for a microbiome study that will be analyzed with pairwise distances and PERMANOVA.

0 comments Cited 180 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome

Ludovic Giloteaux, Julia Goodrich, William Walters … (2016)

Background Gastrointestinal disturbances are among symptoms commonly reported by individuals diagnosed with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). However, whether ME/CFS is associated with an altered microbiome has remained uncertain. Here, we profiled gut microbial diversity by sequencing 16S ribosomal ribonucleic acid (rRNA) genes from stool as well as inflammatory markers from serum for cases (n = 48) and controls (n = 39). We also examined a set of inflammatory markers in blood: C-reactive protein (CRP), intestinal fatty acid-binding protein (I-FABP), lipopolysaccharide (LPS), LPS-binding protein (LBP), and soluble CD14 (sCD14). Results We observed elevated levels of some blood markers for microbial translocation in ME/CFS patients; levels of LPS, LBP, and sCD14 were elevated in ME/CFS subjects. Levels of LBP correlated with LPS and sCD14 and LPS levels correlated with sCD14. Through deep sequencing of bacterial rRNA markers, we identified differences between the gut microbiomes of healthy individuals and patients with ME/CFS. We observed that bacterial diversity was decreased in the ME/CFS specimens compared to controls, in particular, a reduction in the relative abundance and diversity of members belonging to the Firmicutes phylum. In the patient cohort, we find less diversity as well as increases in specific species often reported to be pro-inflammatory species and reduction in species frequently described as anti-inflammatory. Using a machine learning approach trained on the data obtained from 16S rRNA and inflammatory markers, individuals were classified correctly as ME/CFS with a cross-validation accuracy of 82.93 %. Conclusions Our results indicate dysbiosis of the gut microbiota in this disease and further suggest an increased incidence of microbial translocation, which may play a role in inflammatory symptoms in ME/CFS. Electronic supplementary material The online version of this article (doi:10.1186/s40168-016-0171-4) contains supplementary material, which is available to authorized users.

0 comments Cited 147 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

Reduction of butyrate- and methane-producing microorganisms in patients with Irritable Bowel Syndrome

Marta Pozuelo, Suchita Panda, Alba Santiago … (2015)

The pathophysiology of irritable bowel syndrome (IBS) remains unclear. Here we investigated the microbiome of a large cohort of patients to identify specific signatures for IBS subtypes. We examined the microbiome of 113 patients with IBS and 66 healthy controls. A subset of these participants provided two samples one month apart. We analyzed a total of 273 fecal samples, generating more than 20 million 16S rRNA sequences. In patients with IBS, a significantly lower microbial diversity was associated with a lower relative abundance of butyrate-producing bacteria (P = 0.002; q < 0.06), in particular in patients with IBS-D and IBS-M. IBS patients who did not receive any treatment harboured a lower abundance of Methanobacteria compared to healthy controls (P = 0.005; q = 0.05). Furthermore, significant correlations were observed between several bacterial taxa and sensation of flatulence and abdominal pain (P < 0.05). Altogether, our findings showed that IBS-M and IBS-D patients are characterized by a reduction of butyrate producing bacteria, known to improve intestinal barrier function, and a reduction of methane producing microorganisms a major mechanism of hydrogen disposal in the human colon, which could explain excess of abdominal gas in IBS.

0 comments Cited 125 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): BMJ Open

Journal ID (iso-abbrev): BMJ Open

Journal ID (hwp): bmjopen

Journal ID (publisher-id): bmjopen

Title: BMJ Open

Publisher: BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )

ISSN (Electronic): 2044-6055

Publication date Collection: 2019

Publication date (Electronic): 19 August 2019

Volume: 9

Issue: 8

Electronic Location Identifier: e031114

Affiliations

[1 ] departmentResearch , William S Middleton Memorial Veterans Hospital , Madison, Wisconsin, USA

[2 ] departmentDepartment of Medicine, School of Medicine and Public Health , University of Wisconsin Madison , Madison, Wisconsin, USA

[3 ] departmentDepartment of Kinesiology , University of Wisconsin Madison , Madison, Wisconsin, USA

[4 ] departmentDepartment of Family Medicine and Community Health, School of Medicine and Public Health , University of Wisconsin Madison , Madison, Wisconsin, USA

[5 ] departmentDepartment of Bacteriology, College of Agricultural and Life Sciences , University of Wisconsin Madison , Madison, Wisconsin, USA

[6 ] departmentDepartment of Biostatistics and Medical Informatics, School of Medicine and Public Health , University of Wisconsin Madison , Madison, Wisconsin, USA

Author notes

[Correspondence to ] Dr Julie A Keating; julie.keating@ 123456va.gov

Author information

Kelsey Baubie http://orcid.org/0000-0002-6027-7138

Article

Publisher ID: bmjopen-2019-031114

DOI: 10.1136/bmjopen-2019-031114

PMC ID: 6707676

PubMed ID: 31431446

SO-VID: e9b554ef-80a2-41a7-86df-911c88236845

License:

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

History

Date received : 16 April 2019

Date revision received : 16 May 2019

Date accepted : 17 May 2019

Funding

Funded by: FundRef http://dx.doi.org/10.13039/100000738, U.S. Department of Veterans Affairs;

Funded by: FundRef http://dx.doi.org/10.13039/100000092, U.S. National Library of Medicine;

Custom metadata

special-feature unlocked

ScienceOpen disciplines: Medicine

Keywords: internal medicine,gastroenterology,microbiology,pathology

Data availability:

ScienceOpen disciplines: Medicine

Keywords: internal medicine, gastroenterology, microbiology, pathology

Comments

Comment on this article

scite_

Cited by 5

See all cited by

Most referenced authors 647

See all reference authors

Characterising the gut microbiome in veterans with Gulf War Illness: a protocol for a longitudinal, prospective cohort study

Read this article at

Abstract

Introduction

Methods and analysis

Ethics and dissemination

Related collections

Karger: Gastroenterology

Most cited references 23

Power and sample-size estimation for microbiome studies using pairwise distances and PERMANOVA.

Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome

Reduction of butyrate- and methane-producing microorganisms in patients with Irritable Bowel Syndrome

Author and article information

Journal

Affiliations

Author notes

Author information

Article

History

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 253

Cited by 5

Most referenced authors 647