Ranking the impact of human health disorders on gut metabolism: Systemic lupus erythematosus and obesity as study cases

Rojo, David; Hevia, Arancha; Bargiela, Rafael; López, Patricia; Cuervo, Adriana; González, Sonia; Suárez, Ana; Sánchez, Borja; Martínez-Martínez, Mónica; Milani, Christian; Ventura, Marco; Barbas, Coral; Moya, Andrés; Suárez, Antonio; Margollés, Abelardo; Ferrer, Manuel

doi:10.1038/srep08310

Cited by 71 publications

(86 citation statements)

References 34 publications

(70 reference statements)

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“…Many inflammatory and autoimmune diseases are associated with dysbiosis, but whether dysbiosis is the cause or consequence of these diseases is difficult to dissect. Numerous metabolites present in the circulation are dependent on the presence of gut microbiota [53]; thus, it is not surprising that the microbiota can exert effects on the host beyond the gut, including effects on host metabolism, the endocrine system, brain and peripheral immune and inflammatory responses [3,5,6,[58][59][60]. Sequencing of human microbiomes has revealed a wide variation in species composition, thus making it difficult to ascribe beneficial, or detrimental, effects to specific species.…”

Section: Effect Of Commensal Metabolites On Host Immune Functionmentioning

confidence: 99%

Metabolism at the centre of the host–microbe relationship

Maslowski

2019

Clinical and Experimental Immunology

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Summary Maintaining homoeostatic host–microbe interactions is vital for host immune function. The gut microbiota shapes the host immune system and the immune system reciprocally shapes and modifies the gut microbiota. However, our understanding of how these microbes are tolerated and how individual, or communities of, gut microbes influence host function is limited. This review will focus on metabolites as key mediators of this complex host–microbe relationship. It will look at the central role of epithelial metabolism in shaping the gut microbiota, how microbial metabolites influence the epithelium and the mucosal and peripheral immune system, and how the immune system shapes microbial composition and metabolism. Finally, this review will look at how metabolites are involved in cross‐talk between different members of the microbiota and their role during infections.

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Section: Effect Of Commensal Metabolites On Host Immune Functionmentioning

confidence: 99%

Metabolism at the centre of the host–microbe relationship

Maslowski

2019

Clinical and Experimental Immunology

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“…The Firmicutes/Bacteroidetes ratio in patients with SLE was significantly lower than that of healthy subjects (median ratio 1.97 vs median ratio 4.86; P < 0.002), although the bacterial diversity was not significantly different (Hevia et al , ). Another study from the same group performed a metabolome‐wide scan of gut microbiota in patients with SLE and healthy controls (Rojo et al , ). A difference in the gut metabolome (but not in the bacterial composition) was found between patients with SLE and controls, suggesting that SLE affects the functionality of the gut microbiome (Rojo et al , ).…”

Section: The Microbiome–sle Connectionmentioning

confidence: 99%

The microbiome–systemic diseases connection

et al. 2016

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The human microbiome consists of all microorganisms occupying the skin, mucous membranes and intestinal tract of the human body. The contact of the mucosal immune system with the human microbiome is a balanced interplay between defence mechanisms of the immune system and symbiotic or pathogenic microbial factors, such as microbial antigens and metabolites. In systemic autoimmune diseases (SADs) such as rheumatoid arthritis, systemic lupus erythematosus and Sjögren's syndrome, the immune system is deranged to a chronic inflammatory state and autoantibodies are an important hallmark. Specific bacteria and/or a dysbiosis in the human microbiome can lead to local mucosal inflammation and increased intestinal permeability. Proinflammatory lymphocytes and cytokines can spread to the systemic circulation and increase the risk of inflammation at distant anatomical sites, such as the joints or salivary glands. Increased intestinal permeability increases antigen exposure and the risk of autoantibody production. If the human microbiome indeed plays such a critical role in SADs, this finding holds a great promise for new therapeutic strategies, such as diet interventions and probiotics and prebiotics. This review provides a background on the human microbiome and mucosal immunity in the gut and oral cavity and gives a summary of the current knowledge on the microbiome–SADs connection.

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“…Although the statistical significance was not reached (p = 0.095), decreased PCS levels in our patients might indicate the down-regulation of inflammatory and oxidative mechanisms in AOSD. These findings may link the altered microbial metabolites with the pathogenesis of rheumatic diseases [22]. In contrast, we revealed significantly higher levels of L-phenylalanine in patients compared with the control group.…”

Section: Discussionmentioning

confidence: 55%

Metabolic Disturbances in Adult-Onset Still’s Disease Evaluated Using Liquid Chromatography/Mass Spectrometry-Based Metabolomic Analysis

Chen

Chien

et al. 2016

PLoS ONE

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ObjectiveLiquid chromatography/mass spectrometry (LC/MS)-based comprehensive analysis of metabolic profiles with metabolomics approach has potential diagnostic and predictive implications. However, no metabolomics data have been reported in adult-onset Still’s disease (AOSD). This study investigated the metabolomic profiles in AOSD patients and examined their association with clinical characteristics and disease outcome.MethodsSerum metabolite profiles were determined on 32 AOSD patients and 30 healthy controls (HC) using ultra-performance liquid chromatography (UPLC)/MS analysis, and the differentially expressed metabolites were quantified using multiple reactions monitoring (MRM)/MS analysis in 44 patients and 42 HC. Pure standards were utilized to confirm the presence of the differentially expressed metabolites.ResultsEighteen differentially expressed metabolites were identified in AOSD patents using LC/MS-based analysis, of which 13 metabolites were validated by MRM/MS analysis. Among them, serum levels of lysoPC(18:2), urocanic acid and indole were significantly lower, and L-phenylalanine levels were significantly higher in AOSD patients compared with HC. Moreover, serum levels of lysoPC(18:2), PhePhe, uridine, taurine, L-threonine, and (R)-3-Hydroxy-hexadecanoic acid were significantly correlated with disease activity scores (all p<0.05) in AOSD patients. A different clustering of metabolites was associated with a different disease outcome, with significantly lower levels of isovalerylsarcosine observed in patients with chronic articular pattern (median, 77.0AU/ml) compared with monocyclic (341.5AU/ml, p<0.01) or polycyclic systemic pattern (168.0AU/ml, p<0.05).ConclusionThirteen differentially expressed metabolites identified and validated in AOSD patients were shown to be involved in five metabolic pathways. Significant associations of metabolic profiles with disease activity and outcome of AOSD suggest their involvement in AOSD pathogenesis.

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Ranking the impact of human health disorders on gut metabolism: Systemic lupus erythematosus and obesity as study cases

Cited by 71 publications

References 34 publications

Metabolism at the centre of the host–microbe relationship

Metabolism at the centre of the host–microbe relationship

The microbiome–systemic diseases connection

Metabolic Disturbances in Adult-Onset Still’s Disease Evaluated Using Liquid Chromatography/Mass Spectrometry-Based Metabolomic Analysis

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