Metagenomic Analysis of the Pygmy Loris Fecal Microbiome Reveals Unique Functional Capacity Related to Metabolism of Aromatic Compounds

Objective: To investigate whether axial spondyloarthritis (AxSpA) patients have an altered immunoglobulin A (IgA) response in the gut and oral microbial communities. Methods: We performed 16S rRNA gene (16S) sequencing on IgA positive (IgA+) and IgA negative (IgA-) fractions (IgA-SEQ) from feces (n=17 AxSpA; n=14 healthy) and saliva (n=17 AxSpA; n=12 healthy), as well as on IgA-unsorted fecal and salivary samples. PICRUSt2 was used to predict microbial metabolic potential in AxSpA patients and healthy controls (HCs). Results: IgA-SEQ revealed enrichment of several microbes in the fecal (Akkermansia, Ruminococcaceae, Lachnospira) and salivary (Prevotellaceae, Actinobacillus) microbiome in AxSpA patients as compared with HCs. Fecal microbiome from AxSpA patients showed a trend towards increased alpha diversity of the IgA+ fraction and decreased diversity in the IgA- fraction in comparison with HCs, while the salivary microbiome exhibits a significant decrease in alpha diversity in both IgA+ and IgA- fractions. Increased IgA coating of Clostridiales Family XIII correlated with disease severity. Inferred metagenomic analysis suggests perturbation of metabolites and metabolic pathways for inflammation (oxidative phosphorylation, glutathione metabolism) and metabolism (propanoate and butanoate metabolism) in AxSpA patients. Conclusions: Analyses of fecal and salivary microbes from AxSpA patients reveal distinct populations of immunoreactive microbes using novel IgA-SEQ approach, which were not captured by comparing their relative abundance with HCs. Predictive metagenomic analysis revealed perturbation of metabolites/metabolic pathways in AxSpA patients. Future studies on these immunoreactive microbes may lead to better understanding of the functional role of IgA in maintaining microbial structure and human health.

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Abstract P214: Shotgun Metagenomic Analysis of Fecal Microbiome Reveals Profound Functional Differences in Patients with Hypertension

Hypertension ◽

10.1161/hyp.70.suppl_1.p214 ◽

2017 ◽

Vol 70 (suppl_1) ◽

Author(s):

Seungbum Kim ◽

Elaine M Richards ◽

Yanfei Qi ◽

Mohammed Mohammed ◽

Eileen M Handberg ◽

...

Keyword(s):

Nitric Oxide ◽

Web Applications ◽

Metagenomic Analysis ◽

Principal Coordinates Analysis ◽

Kinase Gene ◽

Shotgun Metagenomics ◽

Fecal Microbiome ◽

Microbiome Composition ◽

Principal Coordinates ◽

Significant Difference

Objectives: Recent studies have implicated changes of the gut pathology and altered microbiome in the animals of various hypertension models. However, these relationships in human hypertension are poorly understood. Thus, our objectives in this study was to test the hypothesis that microbiome from hypertensive patients (HTN) would be taxonomically and functionally differ from those of normotensive subjects. Design and Method: Fecal samples were collected from HTN (n=22, mean SBP 155.8±3.4mmHg) and reference subjects without hypertension (REF) (n=18, mean SBP 121.1±1.5mmHg) (see ClinicalTrials.gov, NCT02188381 for detailed protocol). Gut microbiomes were analyzed using shotgun metagenomics and the USEARCH6.1 algorithm for OTU clustering. Taxonomy was assigned with Metaphlan. Qiime, Phyloseq and Galaxy web applications were used to further analyze the data. Results: Two beta diversity measures, principal coordinates analysis and partial least squares discriminant analysis, showed significantly different microbiome composition between the two groups (ANOSIM p=0.012). A heatmap based on significantly enriched functional genes from each cohort (P<0.05) also showed clustering of samples by group. Metagenomic analysis showed that the butyrate kinase gene and the abundance of butyrate producing bacteria were negatively correlated with SBP (R 2 =0.10 and P<0.05 for both). Additionally, functional analysis showed that HEME biosynthesis and hydroxyphenylacetate degradation were decreased in the HTN cohort (LDA score 2.15 and 1.95 respectively) suggesting inefficient nitric oxide synthesis and polyphenol digestion in HTN patients. Conclusions: 1) Significant difference in taxa of HTN from REF was observed. 2) Microbial genes linked to butyrate, nitric oxide and polyphenol were significantly decreased in HTN. Gene products of all these were shown to have important implications in cardiovascular diseases. Thus, our observations suggest that targeting of gut and its microbiota can offer a novel strategy for hypertension control.

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Clinical Update: Functional Capacity Evaluations and Disability

Guides Newsletter ◽

10.1001/amaguidesnewsletters.1998.marapr02 ◽

1998 ◽

Vol 3 (2) ◽

pp. 4-5

Author(s):

Glenn Pransky

Keyword(s):

Direct Observation ◽

Functional Capacity ◽

Work Capacity ◽

Functional Capacity Evaluation ◽

Whole Body ◽

Validity Of Results ◽

Job Tasks ◽

Capacity Evaluation ◽

Physical Abilities ◽

The Relationship

Abstract According to the AMA Guides to the Evaluation of Permanent Impairment, a functional capacity evaluation (FCE) measures an individual's physical abilities via a set of activities in a structured setting and provides objective data about the relationship between an impairment and maximal ability to perform work activities. A key distinction between FCEs and self-reported activities of daily living is that the former involve direct observation by professional evaluators. Numerous devices can quantify the physical function of a specific part of the musculoskeletal system but do not address the performance of whole body tasks in the workplace, and these devices have not been shown to predict accurately the ability to perform all but the simplest job tasks. Information about reliability has been proposed as a way to identify magnification and malingering, but variability due to pain and poor comprehension of instructions may cause variations in assessments. Structured work capacity evaluations involve a set of activities but likely underestimate the individual's ability to do jobs that involve complex or varying activities. Job simulations involve direct observation of an individual performing actual job tasks, require a skilled and experienced evaluator, and raise questions about expense, time, objectivity and validity of results, and interpretation of results in terms of the ability to perform specific jobs. To understand the barriers to return to work, examiners must supplement FCEs with information regarding workplace environment, accommodations, and demotivators.

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Clinical Update: Functional Capacity Evaluations—An Update

Guides Newsletter ◽

10.1001/amaguidesnewsletters.1999.sepoct02 ◽

1999 ◽

Vol 4 (5) ◽

pp. 4-7 ◽

Cited By ~ 1

Author(s):

Laura Welch

Keyword(s):

Job Performance ◽

Functional Capacity ◽

Injury Risk ◽

Disability Evaluation ◽

Time Period ◽

Submaximal Effort ◽

Lack Of Sleep ◽

Overall Performance ◽

Time Required ◽

Specific Limitation

Abstract Functional capacity evaluations (FCEs) have become an important component of disability evaluation during the past 10 years to assess an individual's ability to perform the essential or specific functions of a job, both preplacement and during rehabilitation. Evaluating both job performance and physical ability is a complex assessment, and some practitioners are not yet certain that an FCE can achieve these goals. An FCE is useful only if it predicts job performance, and factors that should be assessed include overall performance; consistency of performance across similar areas of the FCE; consistency between observed behaviors during the FCE and limitations or abilities reported by the worker; objective changes (eg, blood pressure and pulse) that are appropriate relative to performance; external factors (illness, lack of sleep, or medication); and a coefficient of variation that can be measured and assessed. FCEs can identify specific movement patterns or weaknesses; measure improvement during rehabilitation; identify a specific limitation that is amenable to accommodation; and identify a worker who appears to be providing a submaximal effort. FCEs are less reliable at predicting injury risk; they cannot tell us much about endurance over a time period longer than the time required for the FCE; and the FCE may measure simple muscular functions when the job requires more complex ones.

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