1.
Does the microbiome and virome contribute to myalgic encephalomyelitis/chronic fatigue syndrome?
Newberry, F, Hsieh, SY, Wileman, T, Carding, SR
Clinical science (London, England : 1979). 2018;132(5):523-542
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Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) (ME/CFS) is a disabling and debilitating disease. Several studies have shown alterations in the gut microbiome (dysbiosis) in patients with ME/CFS. However, in focusing on the bacterial components of the microbiome, the viral component of the microbiome (known as the virome) has been neglected. Viruses can change the microbiome which can influence the health. This area is therefore important for research into ME/CFS. This article provides a comprehensive review of the current evidence supporting microbiome alterations in ME/CFS patients. Additionally, the challenges associated with microbiome studies are discussed. A literature search was done and 11 papers were found that had examined the microbiome ME/CFS patients, dating from 1998 to 2017. It was not possible to compare the studies statistically but from looking at each one individually there is sufficient evidence to support the claim of an altered intestinal microbiome in ME/CFS patients. ME/CFS is multifactorial and potential dysbiosis should be considered to be only part of the picture. Future studies are needed to adopt standardized techniques and analyses. As research increases, it is becoming clear that the virome can directly and indirectly affect host health, and may play a role in the pathogenesis of ME/CFS.
Abstract
Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) (ME/CFS) is a disabling and debilitating disease of unknown aetiology. It is a heterogeneous disease characterized by various inflammatory, immune, viral, neurological and endocrine symptoms. Several microbiome studies have described alterations in the bacterial component of the microbiome (dysbiosis) consistent with a possible role in disease development. However, in focusing on the bacterial components of the microbiome, these studies have neglected the viral constituent known as the virome. Viruses, particularly those infecting bacteria (bacteriophages), have the potential to alter the function and structure of the microbiome via gene transfer and host lysis. Viral-induced microbiome changes can directly and indirectly influence host health and disease. The contribution of viruses towards disease pathogenesis is therefore an important area for research in ME/CFS. Recent advancements in sequencing technology and bioinformatics now allow more comprehensive and inclusive investigations of human microbiomes. However, as the number of microbiome studies increases, the need for greater consistency in study design and analysis also increases. Comparisons between different ME/CFS microbiome studies are difficult because of differences in patient selection and diagnosis criteria, sample processing, genome sequencing and downstream bioinformatics analysis. It is therefore important that microbiome studies adopt robust, reproducible and consistent study design to enable more reliable and valid comparisons and conclusions to be made between studies. This article provides a comprehensive review of the current evidence supporting microbiome alterations in ME/CFS patients. Additionally, the pitfalls and challenges associated with microbiome studies are discussed.
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The gut microbiome and irritable bowel syndrome.
Menees, S, Chey, W
F1000Research. 2018;7
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This study is a review of role of gut microbiome plays in the pathophysiology of Irritable bowel syndrome (IBS) sufferers. The author’s main objective was to identify the biomarkers that may lead into diagnosing and choosing best available therapy available from various interventions available for IBS that targets the gut microbiome, such as prebiotics, probiotics, non-absorbable antibiotics, diet and faecal microbial transplant (FMT). The authors concluded that to enable the right treatment for IBS sufferers it would be better to understand what constitutes a healthy gut rather than deciphering what is abnormal.
Abstract
Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders encountered in clinical practice. It is a heterogeneous disorder with a multifactorial pathogenesis. Recent studies have demonstrated that an imbalance in gut bacterial communities, or "dysbiosis", may be a contributor to the pathophysiology of IBS. There is evidence to suggest that gut dysbiosis may lead to activation of the gut immune system with downstream effects on a variety of other factors of potential relevance to the pathophysiology of IBS. This review will highlight the data addressing the emerging role of the gut microbiome in the pathogenesis of IBS and review the evidence for current and future microbiome based treatments.
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Fecal Microbiome and Food Allergy in Pediatric Atopic Dermatitis: A Cross-Sectional Pilot Study.
Fieten, KB, Totté, JEE, Levin, E, Reyman, M, Meijer, Y, Knulst, A, Schuren, F, Pasmans, SGMA
International archives of allergy and immunology. 2018;175(1-2):77-84
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Atopic diseases, such as atopic dermatitis (AD), asthma and rhinitis, are on the increase worldwide. Exposure to microbes may be important in the development of an atopic disease. Specifically, reduced early-life exposure is thought to be a contributing factor because microbial colonisation of the intestines during infancy plays a crucial role in the maturation of the immune system. AD, also called eczema, is an inflammatory skin disease often seen in small children. Food allergies are common in children with AD, the most common allergens being eggs, cow’s milk, peanuts, soy and wheat. This cross-sectional observational pilot study with 82 young children with a diagnosis of AD set out to identify distinct microbial patterns in the children’s faecal microbiomes associated with a clinical diagnosis of food allergy. Stool and blood samples were collected for a microbiome analysis and IgE antibody measurement, respectively. 20 children had a confirmed food allergy (most commonly to cow’s milk and peanuts), while almost half of the children without a diagnosed food allergy were sensitised to common food allergens after a food challenge. The study identified a faecal microbial signature in children with AD that differentiates between the presence and absence of food allergy. Children with AD and food allergy had more Escherichia coli and Bifidobacterium pseudocatenulatum species and less Bifidobacterium breve, Faecalibacterium prausnitzii and Akkermansia muciniphila species than children without food allergy. The authors concluded that the study supports a hypothesis that the intestinal microbiome differs in children with AD, depending on whether they have a food allergy or not. They call for future studies to confirm these findings.
Abstract
BACKGROUND Exposure to microbes may be important in the development of atopic disease. Atopic diseases have been associated with specific characteristics of the intestinal microbiome. The link between intestinal microbiota and food allergy has rarely been studied, and the gold standard for diagnosing food allergy (double-blind placebo-controlled food challenge [DBPCFC]) has seldom been used. We aimed to distinguish fecal microbial signatures for food allergy in children with atopic dermatitis (AD). METHODS Pediatric patients with AD, with and without food allergy, were included in this cross-sectional observational pilot study. AD was diagnosed according to the UK Working Party criteria. Food allergy was defined as a positive DBPCFC or a convincing clinical history, in combination with sensitization to the relevant food allergen. Fecal samples were analyzed using 16S rRNA microbial analysis. Microbial signature species, discriminating between the presence and absence food allergy, were selected by elastic net regression. RESULTS Eighty-two children with AD (39 girls) with a median age of 2.5 years, and 20 of whom were diagnosed with food allergy, provided fecal samples. Food allergy to peanut and cow's milk was the most common. Six bacterial species from the fecal microbiome were identified, that, when combined, distinguished between children with and without food allergy: Bifidobacterium breve, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Escherichia coli, Faecalibacterium prausnitzii, and Akkermansia muciniphila (AUC 0.83, sensitivity 0.77, specificity 0.80). CONCLUSIONS In this pilot study, we identified a microbial signature in children with AD that discriminates between the absence and presence of food allergy. Future studies are needed to confirm our findings.
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Navy Beans Impact the Stool Metabolome and Metabolic Pathways for Colon Health in Cancer Survivors.
Baxter, BA, Oppel, RC, Ryan, EP
Nutrients. 2018;11(1)
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Colorectal cancer (CRC) is one of the leading cause of cancer-related death around the world. Emerging evidence supports that increased consumption of pulses / legumes, such as navy beans, can reduce risk. Consuming navy beans as part of one's diet has been previously shown to positively affect the relationship between a person's gut bacteria and their health status. This study looked at stool samples to assess the impact of navy bean consumption on health based on the by-products of metabolism generated by gut bacteria (metabolites). The study was a 4-week, randomised-controlled trial with overweight and obese CRC survivors and involved consumption of 1 meal and 1 snack daily. People in the intervention group ate 35g of cooked navy bean daily whereas those in the control group had 0g of navy beans. From amongst the hundreds of metabolites identified in both groups, there was a 5-fold increase in ophthalmate for navy bean consumers, which can indicate an increase in glutathione. Glutathione is an antioxidant and detoxifying substance produced in the human liver. It is involved in cancer control mechanisms such as detoxification of xenobiotics (toxins), antioxidant defense, proliferation, and apoptosis. Other interesting results include the metabolism of the amino acid lysine, which supports health immune function, and an increase in plant-based nutrients or phytochemicals in those who consumed navy bean vs the control group. These results are indicative of an acute response to increased navy bean intake, which merit further investigation for improving colonic health after long-term consumption.
Abstract
Colorectal cancer (CRC) is the third leading cause of cancer-related death in the United States and emerging evidence supports that increased consumption of legumes, such as navy beans, can reduce risk. Navy bean consumption was previously shown to modulate host and microbiome metabolism, and this investigation was performed to assess the impact on the human stool metabolome, which includes the presence of navy bean metabolites. This 4-week, randomized-controlled trial with overweight and obese CRC survivors involved consumption of 1 meal and 1 snack daily. The intervention contained 35 g of cooked navy bean or macronutrient matched meals and snacks with 0 g of navy beans for the control group (n = 18). There were 30 statistically significant metabolite differences in the stool of participants that consumed navy bean at day 28 compared to the participants' baseline (p ≤ 0.05) and 26 significantly different metabolites when compared to the control group. Of the 560 total metabolites identified from the cooked navy beans, there were 237 possible navy bean-derived metabolites that were identified in the stool of participants consuming navy beans, such as N-methylpipecolate, 2-aminoadipate, piperidine, and vanillate. The microbial metabolism of amino acids and fatty acids were also identified in stool after 4 weeks of navy bean intake including cadaverine, hydantoin-5 propionic acid, 4-hydroxyphenylacetate, and caprylate. The stool relative abundance of ophthalmate increased 5.25-fold for navy bean consumers that can indicate glutathione regulation, and involving cancer control mechanisms such as detoxification of xenobiotics, antioxidant defense, proliferation, and apoptosis. Metabolic pathways involving lysine, and phytochemicals were also modulated by navy bean intake in CRC survivors. These metabolites and metabolic pathways represent an acute response to increased navy bean intake, which merit further investigation for improving colonic health after long-term consumption.
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Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome.
Nagy-Szakal, D, Williams, BL, Mishra, N, Che, X, Lee, B, Bateman, L, Klimas, NG, Komaroff, AL, Levine, S, Montoya, JG, et al
Microbiome. 2017;5(1):44
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Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained persistent fatigue, cognitive dysfunction, sleep disturbances, orthostatic intolerance, fever, swollen lymph glands and irritable bowel syndrome (IBS). It is associated with gut bacterial dysbiosis, systemic inflammation and both gastro intestinal (GI) and neurological disturbances. The extent to which the gastrointestinal microbiome and peripheral inflammation are associated with ME/CFS remains unclear. This experiment looked at fecal bacterial samples and metabolic pathway markers in 50 ME/CFS patients and 50 healthy controls. In ME/CFS subgroups, measures of symptom severity including pain, fatigue, and reduced motivation were correlated with the amounts and types of gut bacteria and certain metabolic pathways. Future prospective studies should consider more detailed exploration of IBS subtypes, associated GI symptoms, and their relationship to ME/CFS dysbiosis. This may enable more accurate diagnosis and the development of specific therapeutic strategies.
Abstract
BACKGROUND Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained persistent fatigue, commonly accompanied by cognitive dysfunction, sleeping disturbances, orthostatic intolerance, fever, lymphadenopathy, and irritable bowel syndrome (IBS). The extent to which the gastrointestinal microbiome and peripheral inflammation are associated with ME/CFS remains unclear. We pursued rigorous clinical characterization, fecal bacterial metagenomics, and plasma immune molecule analyses in 50 ME/CFS patients and 50 healthy controls frequency-matched for age, sex, race/ethnicity, geographic site, and season of sampling. RESULTS Topological analysis revealed associations between IBS co-morbidity, body mass index, fecal bacterial composition, and bacterial metabolic pathways but not plasma immune molecules. IBS co-morbidity was the strongest driving factor in the separation of topological networks based on bacterial profiles and metabolic pathways. Predictive selection models based on bacterial profiles supported findings from topological analyses indicating that ME/CFS subgroups, defined by IBS status, could be distinguished from control subjects with high predictive accuracy. Bacterial taxa predictive of ME/CFS patients with IBS were distinct from taxa associated with ME/CFS patients without IBS. Increased abundance of unclassified Alistipes and decreased Faecalibacterium emerged as the top biomarkers of ME/CFS with IBS; while increased unclassified Bacteroides abundance and decreased Bacteroides vulgatus were the top biomarkers of ME/CFS without IBS. Despite findings of differences in bacterial taxa and metabolic pathways defining ME/CFS subgroups, decreased metabolic pathways associated with unsaturated fatty acid biosynthesis and increased atrazine degradation pathways were independent of IBS co-morbidity. Increased vitamin B6 biosynthesis/salvage and pyrimidine ribonucleoside degradation were the top metabolic pathways in ME/CFS without IBS as well as in the total ME/CFS cohort. In ME/CFS subgroups, symptom severity measures including pain, fatigue, and reduced motivation were correlated with the abundance of distinct bacterial taxa and metabolic pathways. CONCLUSIONS Independent of IBS, ME/CFS is associated with dysbiosis and distinct bacterial metabolic disturbances that may influence disease severity. However, our findings indicate that dysbiotic features that are uniquely ME/CFS-associated may be masked by disturbances arising from the high prevalence of IBS co-morbidity in ME/CFS. These insights may enable more accurate diagnosis and lead to insights that inform the development of specific therapeutic strategies in ME/CFS subgroups.