Gut Microbiota-Dependent Trimethylamine N-Oxide Associates With Inflammation in Common Variable Immunodeficiency

Macpherson, Magnhild Eide; Hov, Johannes Espolin Roksund; Ueland, Thor; Dahl, Tuva B.; Kummen, Martin; Otterdal, Kari; Holm, Kristian; Berge, Rolf K.; Mollnes, Tom Eirik; Trøseid, Marius; Halvorsen, Bente; Aukrust, Pål; Fevang, Børre; Jørgensen, Silje Fjellgård

doi:10.3389/fimmu.2020.574500

Cited by 47 publications

(54 citation statements)

References 47 publications

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“…It is known that intestinal microbiota also play an important role in metabolic diseases with dysregulation of purine metabolism, such as hyperuricemia and gout (67,68). In addition, the decreased levels of adenosine resulted in dysregulation of betaine metabolism (Figure 4A), which is in accordance with observed changes of plasma level of betaine, a precursor of TMAO (triethylamine N-oxide), among CVID patients in Norway (69). Same authors also observed a positive correlation between levels of Hungatella sp.…”

Section: Differences In Cvid Metabolomesupporting

confidence: 78%

Patients With Common Variable Immunodeficiency (CVID) Show Higher Gut Bacterial Diversity and Levels of Low-Abundance Genes Than the Healthy Housemates

Bosák¹,

Lexa²,

Fiedorová³

et al. 2021

Front. Immunol.

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Common variable immunodeficiency (CVID) is a clinically and genetically heterogeneous disorder with inadequate antibody responses and low levels of immunoglobulins including IgA that is involved in the maintenance of the intestinal homeostasis. In this study, we analyzed the taxonomical and functional metagenome of the fecal microbiota and stool metabolome in a cohort of six CVID patients without gastroenterological symptomatology and their healthy housemates. The fecal microbiome of CVID patients contained higher numbers of bacterial species and altered abundance of thirty-four species. Hungatella hathewayi was frequent in CVID microbiome and absent in controls. Moreover, the CVID metagenome was enriched for low-abundance genes likely encoding nonessential functions, such as bacterial motility and metabolism of aromatic compounds. Metabolomics revealed dysregulation in several metabolic pathways, mostly associated with decreased levels of adenosine in CVID patients. Identified features have been consistently associated with CVID diagnosis across the patients with various immunological characteristics, length of treatment, and age. Taken together, this initial study revealed expansion of bacterial diversity in the host immunodeficient conditions and suggested several bacterial species and metabolites, which have potential to be diagnostic and/or prognostic CVID markers in the future.

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Section: Differences In Cvid Metabolomesupporting

confidence: 78%

Patients With Common Variable Immunodeficiency (CVID) Show Higher Gut Bacterial Diversity and Levels of Low-Abundance Genes Than the Healthy Housemates

Bosák¹,

Lexa²,

Fiedorová³

et al. 2021

Front. Immunol.

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“…Regarding the role of gut metabolites in inducing inflammation in CVID patients, Macpherson et al recently showed that high concentrations of the gut microbiota-dependent metabolite trimethylamine N-oxide (TMAO) is associated with systemic inflammation and increased gut microbial abundance of Gammaproteobacteria in CVID patients, suggesting that TMAO could represent a link between systemic inflammation and gut microbial dysbiosis. In this setting, gut microbiota composition may be targeted to reduce systemic inflammation in CVID [ 132 ].…”

Section: Gut Microbiota–host Interactions In Human Inborn Errors Omentioning

confidence: 99%

Gut Microbiota–Host Interactions in Inborn Errors of Immunity

Castagnoli

Pala

Bosticardo

et al. 2021

IJMS

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Inborn errors of immunity (IEI) are a group of disorders that are mostly caused by genetic mutations affecting immune host defense and immune regulation. Although IEI present with a wide spectrum of clinical features, in about one third of them various degrees of gastrointestinal (GI) involvement have been described and for some IEI the GI manifestations represent the main and peculiar clinical feature. The microbiome plays critical roles in the education and function of the host’s innate and adaptive immune system, and imbalances in microbiota-immunity interactions can contribute to intestinal pathogenesis. Microbial dysbiosis combined to the impairment of immunosurveillance and immune dysfunction in IEI, may favor mucosal permeability and lead to inflammation. Here we review how immune homeostasis between commensals and the host is established in the gut, and how these mechanisms can be disrupted in the context of primary immunodeficiencies. Additionally, we highlight key aspects of the first studies on gut microbiome in patients affected by IEI and discuss how gut microbiome could be harnessed as a therapeutic approach in these diseases.

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“…27 studies were considered for this review [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ]. Their major features such as study design, methodology used for TMAO determination, and the effects of foods on TMAO are given in Table 1 .…”

Section: Resultsmentioning

confidence: 99%

“…Rohrmann et al [ 17 ] revealed that meat, egg or fish consumption is not associated with TMAO, choline or betaine concentrations. Thus, a prospective cohort study showed that dietary intake of fish does not significantly impact the TMAO value in immunodeficient subjects [ 35 ].…”

Section: Resultsmentioning

confidence: 99%

“…Tang et al studied the effects on plasma TMAO after a test dose of two hard-boiled eggs and found that patients in the highest quartile for TMAO had a 2.5-fold increase in the three-year risk of myocardial infarction or stroke [ 13 ]. In contrast, studies mainly starting from 2014 have assessed little or no effect of egg consumption on TMAO levels [ 12 , 15 , 17 , 18 , 21 , 22 , 23 , 27 , 31 , 35 , 37 ]. Some of these studies have revealed that plasma choline and betaine increase dose-dependently with egg intake.…”

Section: Resultsmentioning

confidence: 99%

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Association of Urinary and Plasma Levels of Trimethylamine N-Oxide (TMAO) with Foods

Lombardo

Aulisa²,

Marcon³

et al. 2021

Nutrients

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Introduction: Trimethylamine N-oxide (TMAO) may play a key mediator role in the relationship between the diet, gut microbiota and cardiovascular diseases, particularly in people with kidney failure. The aim of this review is to evaluate which foods have a greater influence on blood or urinary trimethylamine N-oxide (TMAO) levels. Methods: 391 language articles were screened, and 27 were analysed and summarized for this review, using the keywords “TMAO” AND “egg” OR “meat” OR “fish” OR “dairy” OR “vegetables” OR “fruit” OR “food” in December 2020. Results: A strong correlation between TMAO and fish consumption, mainly saltwater fish and shellfish, but not freshwater fish, has been demonstrated. Associations of the consumption of eggs, dairy and meat with TMAO are less clear and may depend on other factors such as microbiota or cooking methods. Plant-based foods do not seem to influence TMAO but have been less investigated. Discussion: Consumption of saltwater fish, dark meat fish and shellfish seems to be associated with an increase in urine or plasma TMAO values. Further studies are needed to understand the relationship between increased risk of cardiovascular disease and plasma levels of TMAO due to fish consumption. Interventions coupled with long-term dietary patterns targeting the gut microbiota seem promising.

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Gut Microbiota-Dependent Trimethylamine N-Oxide Associates With Inflammation in Common Variable Immunodeficiency

Cited by 47 publications

References 47 publications

Patients With Common Variable Immunodeficiency (CVID) Show Higher Gut Bacterial Diversity and Levels of Low-Abundance Genes Than the Healthy Housemates

Patients With Common Variable Immunodeficiency (CVID) Show Higher Gut Bacterial Diversity and Levels of Low-Abundance Genes Than the Healthy Housemates

Gut Microbiota–Host Interactions in Inborn Errors of Immunity

Association of Urinary and Plasma Levels of Trimethylamine N-Oxide (TMAO) with Foods

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