Dysbiosis of the intestinal microbiome as a component of pathophysiology in the inborn errors of metabolism

Kirby, Trevor O.; Ochoa‐Repáraz, Javier; Roullet, Jean-Baptiste; Gibson, K. Michael

doi:10.1016/j.ymgme.2020.12.289

Cited by 12 publications

(12 citation statements)

References 73 publications

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“…Several genetic disorders were described in association with dysbiosis. [9][10][11] Dysbiosis is associated with an impaired ability to maintain mucosal membrane function, contributing to systemic inflammation. 12 When dysbiosis occurs, toxins, bacterial endotoxins, bacteria, or debris can leak from the gut, along with food particles containing proteotoxins, such as gluten, casein, and zein, and heat-induced molecules, such as advanced glycation end products and advanced lipoxidation end products.…”

Section: Introductionmentioning

confidence: 99%

The role of bacterial translocation in sepsis: a new target for therapy

Potruch

Schwartz

Ilan

2022

Therap Adv Gastroenterol

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Sepsis is a leading cause of death in critically ill patients, primarily due to multiple organ failures. It is associated with a systemic inflammatory response that plays a role in the pathogenesis of the disease. Intestinal barrier dysfunction and bacterial translocation (BT) play pivotal roles in the pathogenesis of sepsis and associated organ failure. In this review, we describe recent advances in understanding the mechanisms by which the gut microbiome and BT contribute to the pathogenesis of sepsis. We also discuss several potential treatment modalities that target the microbiome as therapeutic tools for patients with sepsis.

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Section: Introductionmentioning

confidence: 99%

The role of bacterial translocation in sepsis: a new target for therapy

Potruch

Schwartz

Ilan

2022

Therap Adv Gastroenterol

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“…One of the most important is the gut with the metabolism of bacteria, which is also influenced by age, lifestyle, and especially nutrition (diet), which is the case for many IEM. The great importance of dysbiosis in IEM has recently been shown by Kirby et al 79 Besides underlying disease, nutrition plays an important role, as demonstrated by the example of two groups of healthy 6‐week‐old infants, one that was fed formula milk compared with the other group, which was breastfed (Figure 15). A metabolomic analysis of 43 urine samples showed differences between the two groups.…”

Section: Critical Evaluation Of Theapplication Of Nmr In the Diagnosi...mentioning

confidence: 93%

Ex vivo proton spectroscopy (¹H‐NMR) analysis of inborn errors of metabolism: Automatic and computer‐assisted analyses

et al. 2022

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There are about 1500 genetic metabolic diseases. A small number of treatable diseases are diagnosed by newborn screening programs, which are continually being developed. However, most diseases can only be diagnosed based on clinical symptoms or metabolic findings. The main biological fluids used are urine, plasma and, in special situations, cerebrospinal fluid. In contrast to commonly used methods such as gas chromatography and high performance liquid chromatography mass spectrometry, ex vivo proton spectroscopy (1H‐NMR) is not yet used in routine clinical practice, although it has been recommended for more than 30 years. Automatic analysis and improved NMR technology have also expanded the applications used for the diagnosis of inborn errors of metabolism. We provide a mini‐overview of typical applications, especially in urine but also in plasma, used to diagnose common but also rare genetic metabolic diseases with 1H‐NMR. The use of computer‐assisted diagnostic suggestions can facilitate interpretation of the profiles. In a proof of principle, to date, 182 reports of 59 different diseases and 500 reports of healthy children are stored. The percentage of correct automatic diagnoses was 74%. Using the same 1H‐NMR profile‐targeted analysis, it is possible to apply an untargeted approach that distinguishes profile differences from healthy individuals. Thus, additional conditions such as lysosomal storage diseases or drug interferences are detectable. Furthermore, because 1H‐NMR is highly reproducible and can detect a variety of different substance categories, the metabolomic approach is suitable for monitoring patient treatment and revealing additional factors such as nutrition and microbiome metabolism. Besides the progress in analytical techniques, a multiomics approach is most effective to combine metabolomics with, for example, whole exome sequencing, to also diagnose patients with nondetectable metabolic abnormalities in biological fluids. In this mini review we also provide our own data to demonstrate the role of NMR in a multiomics platform in the field of inborn errors of metabolism.

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“…Although the prevalence of NCDs in IEMs is variable and the scientific evidence is still incomplete, we believe that IEMs deserve attention in this field. IEMs are predominantly monogenic disorders, but their phenotypic presentation is complex and heterogeneous as they can be the result of either a toxic accumulation of metabolites or deficiency in end products, going to impact different physiological systems ( Kirby et al, 2020 ) also through an imbalance of oxidative state ( Ray and Mukherjee, 2021 ).…”

Section: Iems and Non-communicable Diseases: What’s The Role Of Microbiome?mentioning

confidence: 99%

“…Indeed, dysbiosis, which determines a pro-inflammatory state alongside a condition of increased oxidative stress found in these patients, could be cumulative and concatenated risk factors. The contribution of gut microbiome in causing NCDs is still unclear, but of course an improvement of microbiota composition in anti-inflammatory and anti-oxidative direction can reduce the risk, since dysbiosis could move the clinical phenotype to further exacerbation as a potential patho-genetic mechanism, and it can also represent a preventive action in relation to NCDs ( Kirby et al, 2020 ).…”

Section: Iems and Non-communicable Diseases: What’s The Role Of Microbiome?mentioning

confidence: 99%

Dysbiosis, Host Metabolism, and Non-communicable Diseases: Trialogue in the Inborn Errors of Metabolism

Montanari

Parolisi²,

Borghi

et al. 2021

Front. Physiol.

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Inborn errors of metabolism (IEMs) represent a complex system model, in need of a shift of approach exploring the main factors mediating the regulation of the system, internal or external and overcoming the traditional concept of biochemical and genetic defects. In this context, among the established factors influencing the metabolic flux, i.e., diet, lifestyle, antibiotics, xenobiotics, infectious agents, also the individual gut microbiota should be considered. A healthy gut microbiota contributes in maintaining human health by providing unique metabolic functions to the human host. Many patients with IEMs are on special diets, the main treatment for these diseases. Hence, IEMs represent a good model to evaluate how specific dietary patterns, in terms of macronutrients composition and quality of nutrients, can be related to a characteristic microbiota associated with a specific clinical phenotype (“enterophenotype”). In the present review, we aim at reporting the possible links existing between dysbiosis, a condition reported in IEMs patients, and a pro-inflammatory status, through an altered “gut-liver” cross-talk network and a major oxidative stress, with a repercussion on the health status of the patient, increasing the risk of non-communicable diseases (NCDs). On this basis, more attention should be paid to the nutritional status assessment and the clinical and biochemical signs of possible onset of comorbidities, with the goal of improving the long-term wellbeing in IEMs. A balanced intestinal ecosystem has been shown to positively contribute to patient health and its perturbation may influence the clinical spectrum of individuals with IEMs. For this, reaching eubiosis through the improvement of the quality of dietary products and mixtures, the use of pre-, pro- and postbiotics, could represent both a preventive and therapeutic strategy in these complex diseases.

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Dysbiosis of the intestinal microbiome as a component of pathophysiology in the inborn errors of metabolism

Cited by 12 publications

References 73 publications

The role of bacterial translocation in sepsis: a new target for therapy

The role of bacterial translocation in sepsis: a new target for therapy

Ex vivo proton spectroscopy (¹H‐NMR) analysis of inborn errors of metabolism: Automatic and computer‐assisted analyses

Dysbiosis, Host Metabolism, and Non-communicable Diseases: Trialogue in the Inborn Errors of Metabolism

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Dysbiosis of the intestinal microbiome as a component of pathophysiology in the inborn errors of metabolism

Cited by 12 publications

References 73 publications

The role of bacterial translocation in sepsis: a new target for therapy

The role of bacterial translocation in sepsis: a new target for therapy

Ex vivo proton spectroscopy (1H‐NMR) analysis of inborn errors of metabolism: Automatic and computer‐assisted analyses

Dysbiosis, Host Metabolism, and Non-communicable Diseases: Trialogue in the Inborn Errors of Metabolism

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Ex vivo proton spectroscopy (¹H‐NMR) analysis of inborn errors of metabolism: Automatic and computer‐assisted analyses