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Enriched Marine Oil Supplement Increases Specific Plasma Specialized Pro-Resolving Mediators in Adults with Obesity.
Al-Shaer, AE, Regan, J, Buddenbaum, N, Tharwani, S, Drawdy, C, Behee, M, Sergin, S, Fenton, JI, Maddipati, KR, Kane, S, et al
The Journal of nutrition. 2022;152(7):1783-1791
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Specialised pro-resolving mediators (SPMs) are highly potent oxylipins [metabolites] synthesized from omega-3 and omega-6 polyunsaturated fatty acids. SPMs have a critical role in resolving inflammation and returning damaged tissues to homeostasis. The main aim of this study was to determine if a marine oil supplement increased specific metabolites of the SPM biosynthetic pathway in adults with obesity. This study is a non-randomised uncontrolled clinical trial in adults with obesity. Twenty-three participants (n = 13 females, 10 males) aged between 50–65 years were enrolled. Only postmenopausal females were included in order to reduce confounding effects of oestrogen on lipid metabolism during supplementation. Results show that: - the marine oil supplement significantly increased some oxylipins of the SPM biosynthetic pathway. - there wasn’t an increase in the concentration of D-series resolvins upon intervention, although several docosahexaenoic acid-derived metabolites were increased. - the supplement decreased some HETEs [metabolites], which are synthesized from arachidonic acid. Authors conclude that their findings provide a framework for futures studies on the use of a marine oil supplement to examine the effects of how SPMs and their metabolic intermediates control varying aspects of inflammation and immunity, including antibody concentrations, in subjects with obesity.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Marine oil enriched with specialised pro-resolving mediators raise levels of EPA, DPA and DHA-metabolites in adult subjects with obesity
- Larger randomised, blinded and placebo-controlled trials are required to inform healthcare practitioner clinical practice decisions relating to SPM enriched marine oil supplementation
- Future research is required to determine if increased concentrations of SPMs control the resolution of inflammation in humans with obesity.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
- Specialised pro-resolving mediators (SPMs) are oxylipins synthesised from omega-3 and -6 PUFAs which play a role in resolving inflammation.
- The authors highlight mouse studies have found that increasing the levels of SPMs and their metabolic intermediates can improve a range of obesity related complications. Thus, there is scientific interest in increasing the levels of SPMs in humans with diseases associated with chronic inflammation, such as obesity.
- This small non-randomised uncontrolled clinical trial of 23 individuals (13 female; 10 male) aged 50-65 years with obesity (BMI 30-40), aimed to determine the impacts of 1 month supplementation with marine oil particularly enriched with 14-hydroxydocosahexanenoic acid (14-HDHA), 17-HDHA and 18-hydroxydocosahenaenoic acid (HEPE) on:
- The change in levels of PUFA-derived oxylipins from baseline
- The change in abundance of circulating peripheral blood mononuclear cells (PBMCs)
- The change in antibody production
Intervention
- 2g enriched marine oil (4 capsules of SPM Active provided by Metagenics, study sponsor) once daily for 28-30 consecutive days.
Inclusion/Exclusion Criteria
- Only post-menopausal women were included to reduce confounding effects of oestrogen on lipid metabolism
- Individuals were excluded if diagnosed with Type 1 or 2 diabetes, autoimmunity, liver disease, coagulopathy, uncontrolled hypothyroid or active malignancy
- Individuals were excluded if they consumed omega-3 PUFA supplements within 3 months of intervention, regularly consumed >2 servings per week of fatty fish, had a fish/shellfish allergy or were taking a predetermined list of medications.
Findings
- Statistically significant increases were found in certain EPA, DPA and DHA-derived metabolites in response to supplementation relative to baseline. However, only 17-HDHA concentrations increased relative to baseline, with no effect on 14-HDHA or 18-HEPE, despite the supplement being enriched with all 3 metabolites
- Statistically significant decreases were found in arachidonic acid (AA)-derived oxylipins post supplementation relative to baseline
- Increases in immune cell populations in circulation did not reach significance post supplementation when measured by PBMCs.
Conclusions
An enriched marine oil supplement increased select SPMs in adults with obesity.
Clinical practice applications:
- Healthcare practitioners working with adults with obesity can use the results from this trial to understand that 1 month supplementation with 4g of enriched marine oil supplementation raises levels of certain EPA, DPA and DHA metabolites
- Practitioners may want to follow the research in this area as larger, controlled trials are conducted and comparisons made with non-enriched fatty acid supplements.
Considerations for future research:
- Future clinical studies of SPM supplementation are required that are double-blind, randomised and placebo-controlled to inform scientific findings in this area
- This study was inadequately powered to assess differences between female and male participants and therefore larger trials are needed to inform the sex differences in oxylipins within the population with obesity
- Further research is required in younger subjects with obesity to assess SPMs as a possible chronic inflammation preventative strategy, due to inflammation complications over time
- Future research should take account of the heterogeneity in the population with obesity, such as microbiome profiles, food intake and baseline metabolic status
- Further studies comparing impacts of standard marine oil with enriched marine oil on chronic inflammation would inform healthcare practitioners in their clinical practice.
Abstract
BACKGROUND Specialized pro-resolving mediators (SPMs), synthesized from PUFAs, resolve inflammation and return damaged tissue to homeostasis. Thus, increasing metabolites of the SPM biosynthetic pathway may have potential health benefits for select clinical populations, such as subjects with obesity who display dysregulation of SPM metabolism. However, the concentrations of SPMs and their metabolic intermediates in humans with obesity remains unclear. OBJECTIVES The primary objective of this study was to determine if a marine oil supplement increased specific metabolites of the SPM biosynthetic pathway in adults with obesity. The second objective was to determine if the supplement changed the relative abundance of key immune cell populations. Finally, given the critical role of antibodies in inflammation, we determined if ex vivo CD19 + B-cell antibody production was modified by marine oil intervention. METHODS Twenty-three subjects [median age: 56 y; BMI (in kg/m2): 33.1] consumed 2 g/d of a marine oil supplement for 28-30 d. The supplement was particularly enriched with 18-hydroxyeicosapentaenoic (HEPE), 14-hydroxydocosahexaenoic acid (14-HDHA), and 17-HDHA. Blood was collected pre- and postsupplementation for plasma mass spectrometry oxylipin and fatty acid analyses, flow cytometry, and B-cell isolation. Paired t-tests and Wilcoxon tests were used for statistical analyses. RESULTS Relative to preintervention, the supplement increased 6 different HEPEs and HDHAs accompanied by changes in plasma PUFAs. Resolvin E1 and docosapentaenoic acid-derived maresin 1 concentrations were increased 3.5- and 4.7-fold upon intervention, respectively. The supplement did not increase the concentration of D-series resolvins and had no effect on the abundance of immune cells. Ex vivo B-cell IgG but not IgM concentrations were lowered postsupplementation. CONCLUSIONS A marine oil supplement increased select SPMs and their metabolic intermediates in adults with obesity. Additional studies are needed to determine if increased concentrations of specific SPMs control the resolution of inflammation in humans with obesity. This trial was registered at clinicaltrials.gov as NCT04701138.
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Naturalization of the microbiota developmental trajectory of Cesarean-born neonates after vaginal seeding.
Song, SJ, Wang, J, Martino, C, Jiang, L, Thompson, WK, Shenhav, L, McDonald, D, Marotz, C, Harris, PR, Hernandez, CD, et al
Med (New York, N.Y.). 2021;2(8):951-964.e5
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Studies on model organisms show that foetal development can be modulated by microbial products from the pregnant mother’s microbiota, and early colonisation is critical for immune system development. However, natural transmission and colonisation of maternal microbes is impaired by caesarean section (CS) delivery. The aim of this study was to determine the effect of restoring exposure to maternal vaginal fluids after CS birth. This study is a large observational study of 177 infants born to 174 mothers. Physicians assessed healthy mothers who were set to deliver vaginally or by scheduled CS. Results demonstrate that microbial differences associated with delivery mode can be reduced by exposure to a vaginal microbial source at birth. In fact, birth mode significantly differentiated infant gut and skin microbiome development, and that seeding worked to adjust the trajectory of CS-delivered infants through partial restoration of microbiome features associated with a vaginal delivery. Authors conclude that restoring natural exposures at birth may be one way to reduce the risk of CS-associated diseases such as obesity, asthma, allergies, and immune disfunctions. However, randomised clinical trials on large cohorts are needed to gain conclusive evidence for microbial restoration at birth improving health outcomes.
Abstract
BACKGROUND Early microbiota perturbations are associated with disorders that involve immunological underpinnings. Cesarean section (CS)-born babies show altered microbiota development in relation to babies born vaginally. Here we present the first statistically powered longitudinal study to determine the effect of restoring exposure to maternal vaginal fluids after CS birth. METHODS Using 16S rRNA gene sequencing, we followed the microbial trajectories of multiple body sites in 177 babies over the first year of life; 98 were born vaginally, and 79 were born by CS, of whom 30 were swabbed with a maternal vaginal gauze right after birth. FINDINGS Compositional tensor factorization analysis confirmed that microbiota trajectories of exposed CS-born babies aligned more closely with that of vaginally born babies. Interestingly, the majority of amplicon sequence variants from maternal vaginal microbiomes on the day of birth were shared with other maternal sites, in contrast to non-pregnant women from the Human Microbiome Project (HMP) study. CONCLUSIONS The results of this observational study prompt urgent randomized clinical trials to test whether microbial restoration reduces the increased disease risk associated with CS birth and the underlying mechanisms. It also provides evidence of the pluripotential nature of maternal vaginal fluids to provide pioneer bacterial colonizers for the newborn body sites. This is the first study showing long-term naturalization of the microbiota of CS-born infants by restoring microbial exposure at birth. FUNDING C&D, Emch Fund, CIFAR, Chilean CONICYT and SOCHIPE, Norwegian Institute of Public Health, Emerald Foundation, NIH, National Institute of Justice, Janssen.
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A randomized, phase 1, placebo-controlled trial of APG-157 in oral cancer demonstrates systemic absorption and an inhibitory effect on cytokines and tumor-associated microbes.
Basak, SK, Bera, A, Yoon, AJ, Morselli, M, Jeong, C, Tosevska, A, Dong, TS, Eklund, M, Russ, E, Nasser, H, et al
Cancer. 2020;126(8):1668-1682
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APG-157 is a botanical drug containing multiple polyphenols that delivers the active components to oromucosal tissues near the tumour target. APG-157 slowly disintegrates in the oral cavity over 15 to 20 minutes to release the drug substance. The drug substance is a precise, rational combination of multiple molecules derived from Curcuma longa wherein curcumin is the principal component. The main aim of this study was to determine the pharmacokinetics and safety of the orally delivered pastille (APG-157) when used by normal subjects and patients with cancer. This study is a randomised, double-blind, placebo-controlled trial. A total of 32 subjects were enrolled, and 25 completed the study (13 normal individuals and 12 patients with oral cancer). Results demonstrated that transoral APG-157 treatment leads to systemic absorption of curcumin and its analogs. There was a statistically significant concentration reduction in inflammatory cytokines and Bacteroides species noted in the salivary cells. Pre-treatment and post-treatment tumour samples from patients with cancer demonstrated T-cell recruitment to the tumour microenvironment. Authors conclude that APG-157 is absorbed well, reduces inflammation, and attracts T-cells to the tumour thus, it can be potentially used in combination with immunotherapy drugs. Furthermore, a long-term evaluation of immune checkpoint blockade with and without APG-157 could provide a clear understanding of the usefulness of APG-157 as either an adjuvant or neoadjuvant therapeutic agent for patients with advanced or recurrent head and neck cancer.
Abstract
BACKGROUND Although curcumin's effect on head and neck cancer has been studied in vitro and in vivo, to the authors' knowledge its efficacy is limited by poor systemic absorption from oral administration. APG-157 is a botanical drug containing multiple polyphenols, including curcumin, developed under the US Food and Drug Administration's Botanical Drug Development, that delivers the active components to oromucosal tissues near the tumor target. METHODS A double-blind, randomized, placebo-controlled, phase 1 clinical trial was conducted with APG-157 in 13 normal subjects and 12 patients with oral cancer. Two doses, 100 mg or 200 mg, were delivered transorally every hour for 3 hours. Blood and saliva were collected before and 1 hour, 2 hours, 3 hours, and 24 hours after treatment. Electrocardiograms and blood tests did not demonstrate any toxicity. RESULTS Treatment with APG-157 resulted in circulating concentrations of curcumin and analogs peaking at 3 hours with reduced IL-1β, IL-6, and IL-8 concentrations in the salivary supernatant fluid of patients with cancer. Salivary microbial flora analysis showed a reduction in Bacteroidetes species in cancer subjects. RNA and immunofluorescence analyses of tumor tissues of a subject demonstrated increased expression of genes associated with differentiation and T-cell recruitment to the tumor microenvironment. CONCLUSIONS The results of the current study suggested that APG-157 could serve as a therapeutic drug in combination with immunotherapy. LAY SUMMARY Curcumin has been shown to suppress tumor cells because of its antioxidant and anti-inflammatory properties. However, its effectiveness has been limited by poor absorption when delivered orally. Subjects with oral cancer were given oral APG-157, a botanical drug containing multiple polyphenols, including curcumin. Curcumin was found in the blood and in tumor tissues. Inflammatory markers and Bacteroides species were found to be decreased in the saliva, and immune T cells were increased in the tumor tissue. APG-157 is absorbed well, reduces inflammation, and attracts T cells to the tumor, suggesting its potential use in combination with immunotherapy drugs.
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Pharmaceutical Interventions in Chronic Fatigue Syndrome: A Literature-based Commentary.
Richman, S, Morris, MC, Broderick, G, Craddock, TJA, Klimas, NG, Fletcher, MA
Clinical therapeutics. 2019;41(5):798-805
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Myalgic encephalomyelitis, also known as Chronic Fatigue Syndrome (ME/ CFS), is a disease characterized by an inability to exert oneself physically, often coupled with a combination of other symptoms, including sleep disorders, severe unpredictable pain, and compromised cognitive abilities. The aim of this review was to delineate a number of the more prominent treatments for ME/CFS into different categories and evaluate the methods and results of corresponding drug trials. Results indicate that: • antiviral drugs appear to show limited efficacy in treating ME/CFS over a broad demographic. • there is a lack of clinical research focusing on the use of specific cyclooxygenase-2 inhibitors [analgesic] to treat ME/CFS. • antidepressants may be of use in delivering improvements in the quality of life of patients with ME/CFS. • recalibration of endocrine-immune regulation may be involved in supporting the persistence of ME/CFS and may be responsible at least in part for its resistance to single agent interventions. Authors conclude that there is a great need for larger, longitudinal studies focused on a more clearly defined subset of ME/CFS as well as a greater consideration of potential synergies between interventions and the suitability of combination therapies.
Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disorder characterized by prolonged periods of fatigue, chronic pain, depression, and a complex constellation of other symptoms. Currently, ME/CFS has no known cause, nor are the mechanisms of illness well understood. Therefore, with few exceptions, attempts to treat ME/CFS have been directed mainly toward symptom management. These treatments include antivirals, pain relievers, antidepressants, and oncologic agents as well as other single-intervention treatments. Results of these trials have been largely inconclusive and, in some cases, contradictory. Contributing factors include a lack of well-designed and -executed studies and the highly heterogeneous nature of ME/CFS, which has made a single etiology difficult to define. Because the majority of single-intervention treatments have shown little efficacy, it may instead be beneficial to explore broader-acting combination therapies in which a more focused precision-medicine approach is supported by a systems-level analysis of endocrine and immune co-regulation.
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Maternal diet during pregnancy is related with the infant stool microbiome in a delivery mode-dependent manner.
Lundgren, SN, Madan, JC, Emond, JA, Morrison, HG, Christensen, BC, Karagas, MR, Hoen, AG
Microbiome. 2018;6(1):109
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The mechanism by which the maternal diet may influence the gut microbiota of an infant remains unknown. This study aimed to examine the association of maternal diet during pregnancy and mode of delivery on the gut microbiome 6 weeks post-delivery. 976 subjects were enrolled aged of 18 and 45 years old, between 24 and 28 weeks of gestation and their maternal diet during pregnancy was assessed with a validated food frequency questionnaire. Effects of maternal dairy intake on infant gut microbiota showed decreased colonization of milk-digesting bacteria in infants delivered by caesarean section, when compared to those who were born vaginally. The authors concluded that future studies examining the relationship between maternal diet and components of breast milk including microbial and nutritional profiles, may help to offer insight into the mechanism by which maternal diet influences the gut microbiome of an infant.
Abstract
BACKGROUND The gut microbiome has an important role in infant health and immune development and may be affected by early-life exposures. Maternal diet may influence the infant gut microbiome through vertical transfer of maternal microbes to infants during vaginal delivery and breastfeeding. We aimed to examine the association of maternal diet during pregnancy with the infant gut microbiome 6 weeks post-delivery in mother-infant dyads enrolled in the New Hampshire Birth Cohort Study. Infant stool samples were collected from 145 infants, and maternal prenatal diet was assessed using a food frequency questionnaire. We used targeted sequencing of the 16S rRNA V4-V5 hypervariable region to characterize infant gut microbiota. To account for differences in baseline and trajectories of infant gut microbial profiles, we stratified analyses by delivery mode. RESULTS We identified three infant gut microbiome clusters, characterized by increased abundance of Bifidobacterium, Streptococcus and Clostridium, and Bacteroides, respectively, overall and in the vaginally delivered infant stratum. In the analyses stratified to infants born vaginally and adjusted for other potential confounders, maternal fruit intake was associated with infant gut microbial community structure (PERMANOVA, p < 0.05). In multinomial logistic regression analyses, increased fruit intake was associated with an increased odds of belonging to the high Streptococcus/Clostridium group among infants born vaginally (OR (95% CI) = 2.73 (1.36, 5.46)). In infants delivered by Cesarean section, we identified three clusters that differed slightly from vaginally delivered infants, which were characterized by a high abundance of Bifidobacterium, high Clostridium and low Streptococcus and Ruminococcus genera, and high abundance of the family Enterobacteriaceae. Maternal dairy intake was associated with an increased odds of infants belonging to the high Clostridium cluster in infants born by Cesarean section (OR (95% CI) = 2.36 (1.05, 5.30)). Linear models suggested additional associations between maternal diet and infant intestinal microbes in both delivery mode strata. CONCLUSIONS Our data indicate that maternal diet influences the infant gut microbiome and that these effects differ by delivery mode.
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Human Gut Microbiota and Gastrointestinal Cancer.
Meng, C, Bai, C, Brown, TD, Hood, LE, Tian, Q
Genomics, proteomics & bioinformatics. 2018;16(1):33-49
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In this article the authors review research on the influence of the human gut microbiota on the development and progression of gastrointestinal cancers, and go into significant detail about the molecular mechanisms involved. Helicobacter pylori is a known risk factor for gastric cancer (GC) but other dysbiotic changes in the gut microbiota are also observed in GC. On the other hand, H. pylori is associated with a decreased risk for oesophageal cancer (OC). An increase in gram-negative bacteria is associated with OC, whilst gram-positive bacteria are dominant in a healthy oesophagus. Dietary factors are associated with the risk for colorectal cancer (CRC) and may be due to their effect on the bacterial composition of the bowel. The authors explore possible mechanisms for these links. Although the liver is considered sterile, carcinogenesis can be influenced by the gut microbiota through pathogens and bacterial metabolites which can disturb metabolic pathways and immune responses in the liver. In pancreatic cancer (PC), the gut microbiota may influence carcinogenesis by promoting inflammation. In addition to various lifestyle factors, H. pylori is a risk factor for PC. The authors also review the use of prebiotics, probiotics, synbiotics (a combination of pre- and pro-biotics) and Traditional Chinese Medicine as an adjunct to conventional cancer treatment to reduce side effects, as well as their potential preventive mechanisms.
Abstract
Human gut microbiota play an essential role in both healthy and diseased states of humans. In the past decade, the interactions between microorganisms and tumors have attracted much attention in the efforts to understand various features of the complex microbial communities, as well as the possible mechanisms through which the microbiota are involved in cancer prevention, carcinogenesis, and anti-cancer therapy. A large number of studies have indicated that microbial dysbiosis contributes to cancer susceptibility via multiple pathways. Further studies have suggested that the microbiota and their associated metabolites are not only closely related to carcinogenesis by inducing inflammation and immune dysregulation, which lead to genetic instability, but also interfere with the pharmacodynamics of anticancer agents. In this article, we mainly reviewed the influence of gut microbiota on cancers in the gastrointestinal (GI) tract (including esophageal, gastric, colorectal, liver, and pancreatic cancers) and the regulation of microbiota by diet, prebiotics, probiotics, synbiotics, antibiotics, or the Traditional Chinese Medicine. We also proposed some new strategies in the prevention and treatment of GI cancers that could be explored in the future. We hope that this review could provide a comprehensive overview of the studies on the interactions between the gut microbiota and GI cancers, which are likely to yield translational opportunities to reduce cancer morbidity and mortality by improving prevention, diagnosis, and treatment.
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Substituting whole grains for refined grains in a 6-wk randomized trial has a modest effect on gut microbiota and immune and inflammatory markers of healthy adults.
Vanegas, SM, Meydani, M, Barnett, JB, Goldin, B, Kane, A, Rasmussen, H, Brown, C, Vangay, P, Knights, D, Jonnalagadda, S, et al
The American journal of clinical nutrition. 2017;105(3):635-650
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Increased whole grain consumption has been associated with reduced levels of inflammation. This randomised, controlled trial aimed to assess the effects of a whole grain diet in comparison with a refined grain diet on the immune system, levels of inflammation and gut bacteria. 81 men and women aged between 40 and 60 were randomly assigned to either a whole grain or a refined grain diet for a period of 6 weeks. All other dietary components were kept the same and calorie levels were controlled to maintain weight levels. The study findings showed a positive effect on stool frequency and stool weight with the whole grain diet in comparison to the refined grain diet. The whole grain diet also showed modest positive effects on gut bacteria profiles and aspects of immunity. The whole grain diet showed no effects on markers of inflammation.
Abstract
Background: Observational studies suggest an inverse association between whole-grain (WG) consumption and inflammation. However, evidence from interventional studies is limited, and few studies have included measurements of cell-mediated immunity.Objective: We assessed the effects of diets rich in WGs compared with refined grains (RGs) on immune and inflammatory responses, gut microbiota, and microbial products in healthy adults while maintaining subject body weights.Design: After a 2-wk provided-food run-in period of consuming a Western-style diet, 49 men and 32 postmenopausal women [age range: 40-65 y, body mass index (in kg/m2) <35] were assigned to consume 1 of 2 provided-food weight-maintenance diets for 6 wk.Results: Compared with the RG group, the WG group had increased plasma total alkyresorcinols (a measure of WG intake) (P < 0.0001), stool weight (P < 0.0001), stool frequency (P = 0.02), and short-chain fatty acid (SCFA) producer Lachnospira [false-discovery rate (FDR)-corrected P = 0.25] but decreased pro-inflammatory Enterobacteriaceae (FDR-corrected P = 0.25). Changes in stool acetate (P = 0.02) and total SCFAs (P = 0.05) were higher in the WG group than in the RG group. A positive association was shown between Lachnospira and acetate (FDR-corrected P = 0.002) or butyrate (FDR-corrected P = 0.005). We also showed that there was a higher percentage of terminal effector memory T cells (P = 0.03) and LPS-stimulated ex vivo production of tumor necrosis factor-α (P = 0.04) in the WG group than in the RG group, which were positively associated with plasma alkylresorcinol concentrations.Conclusion: The short-term consumption of WGs in a weight-maintenance diet increases stool weight and frequency and has modest positive effects on gut microbiota, SCFAs, effector memory T cells, and the acute innate immune response and no effect on other markers of cell-mediated immunity or systemic and gut inflammation. This trial was registered at clinicaltrials.gov as NCT01902394.
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Tracking post-infectious fatigue in clinic using routine Lab tests.
Harvey, JM, Broderick, G, Bowie, A, Barnes, ZM, Katz, BZ, O'Gorman, MRG, Vernon, SD, Fletcher, MA, Klimas, NG, Taylor, R
BMC pediatrics. 2016;16:54
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Chronic fatigue syndrome (CFS) is a complex disease with many different symptoms and there are no definitive tests for diagnosis. This cohort study of 301 adolescents, who had suffered a viral infection, aimed to analyse several commonly used biological markers to determine who may experience CFS symptoms. The results showed variations in several biomarkers, however, decreases in hormones related to the stress response were highly predictive of CFS. Sex hormones and the proportion of immune cells were also markedly disrupted. It was concluded that assessing stress hormones, sex hormones and the proportion of immune cells could be used to diagnose CFS following a viral infection. This study could be used by healthcare professionals to understand that several commonly tested biomarkers could be potentially used to diagnose post-viral CFS.
Abstract
BACKGROUND While biomarkers for chronic fatigue syndrome (CFS) are beginning to emerge they typically require a highly specialized clinical laboratory. We hypothesized that subsets of commonly measured laboratory markers used in combination could support the diagnosis of post-infectious CFS (PI-CFS) in adolescents following infectious mononucleosis (IM) and help determine who might develop persistence of symptoms. METHODS Routine clinical laboratory markers were collected prospectively in 301 mono-spot positive adolescents, 4 % of whom developed CFS (n = 13). At 6, 12, and 24 months post-diagnosis with IM, 59 standard tests were performed including metabolic profiling, liver enzyme panel, hormone profiles, complete blood count (CBC), differential white blood count (WBC), salivary cortisol, and urinalysis. Classification models separating PI-CFS from controls were constructed at each time point using stepwise subset selection. RESULTS Lower ACTH levels at 6 months post-IM diagnosis were highly predictive of CFS (AUC p = 0.02). ACTH levels in CFS overlapped with healthy controls at 12 months, but again showed a trend towards a deficiency at 24 months. Conversely, estradiol levels depart significantly from normal at 12 months only to recover at 24 months (AUC p = 0.02). Finally, relative neutrophil count showed a significant departure from normal at 24 months in CFS (AUC p = 0.01). Expression of these markers evolved differently over time between groups. CONCLUSIONS Preliminary results suggest that serial assessment of stress and sex hormones as well as the relative proportion of innate immune cells measured using standard clinical laboratory tests may support the diagnosis of PI-CFS in adolescents with IM.