Special Issue "Nutrition, Gut Microbiome/Metabolome and Immune System: Prospects for Non-Communicable Diseases"

A special issue of Biomolecules (ISSN 2218-273X).

Deadline for manuscript submissions: 15 February 2022.

Special Issue Editors

Dr. Monika Cahová
E-Mail Website
Guest Editor
Institutu Klinické a Experimentální Medicíny, Prague, Czech Republic
Interests: gut microbiome; gut metabolome; metabolic diseases; plant-based diets
Dr. Jan Gojda
E-Mail Website
Guest Editor
Centre for Research on Diabetes, Metabolism and Nutrition, Charles University in Prague, Prague, Czech Republic
Interests: plant-based diets; nutrition; type 2 diabetes; human physiology
Dr. Marek Kuzma
E-Mail Website
Guest Editor
Institute of Microbiology, Czech Academy of Science, Prague, Czech Republic
Interests: metabolomics; nuclear magnetic resonance; mass spectrometry; obesity; type 2 diabetes

Special Issue Information

Dear Colleagues,

Dietary factors, gut microbiota, and their mechanisms of action are gaining increasing attention in the field, as they affect numerous biological functions throughout the body. They may play a fundamental role in developing or preventing many non-communicable diseases (NCD), such as obesity, diabetes, cardiovascular disease, neurological diseases, and cancer. There are numerous forms of microbiota: host interactions, mediated by direct contact with gut mucosa, the interplay of dietary components and microbiota, and remote signaling via specific biomolecules, i.e., microbial fermentation products. An unanswered but highly topical question became the definition of “healthy microbiome” and the interrelationship between the microbiome and different dietary patterns. As such, dietary manipulations, microbiota, and their mechanisms of action represent promising preventive strategies, as well as potential therapeutic tools. We aim to provide updated state-of-the-art knowledge of emerging concepts and novel challenging therapeutic perspectives and avenues in the field. This Special Issue will focus on the wide variety of aspects of dietary and microbiome host interactions related to the initiation and development or prevention and treatment of NCD. Original manuscripts, reviews, or short communications dealing with any aspect of this topic are very much invited to submission.

Dr. Monika Cahová
Dr. Jan Gojda
Dr. Marek Kuzma
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2100 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • gut microbiome/metabolome
  • nutrition
  • non-communicable diseases
  • healthy microbiome
  • microbiome-based therapy

Published Papers (4 papers)

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Research

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Article
The Effect of Mycotoxins and Silymarin on Liver Lipidome of Mice with Non-Alcoholic Fatty Liver Disease
Biomolecules 2021, 11(11), 1723; https://doi.org/10.3390/biom11111723 - 19 Nov 2021
Cited by 1 | Viewed by 426
Abstract
Milk thistle-based dietary supplements have become increasingly popular. The extract from milk thistle (Silybum marianum) is often used for the treatment of liver diseases because of the presence of its active component, silymarin. However, the co-occurrence of toxic mycotoxins in these [...] Read more.
Milk thistle-based dietary supplements have become increasingly popular. The extract from milk thistle (Silybum marianum) is often used for the treatment of liver diseases because of the presence of its active component, silymarin. However, the co-occurrence of toxic mycotoxins in these preparations is quite frequent as well. The objective of this study was to investigate the changes in composition of liver lipidome and other clinical characteristics of experimental mice fed by a high-fat methionine-choline deficient diet inducing non-alcoholic fatty liver disease. The mice were exposed to (i) silymarin, (ii) mycotoxins (trichothecenes, enniatins, beauvericin, and altertoxins) and (iii) both silymarin and mycotoxins, and results were compared to the controls. The liver tissue extracts were analyzed by ultra-high performance liquid chromatography coupled with high-resolution tandem mass spectrometry. Using tools of univariate and multivariate statistical analysis, we were able to identify 48 lipid species from the classes of diacylglycerols, triacylglycerols, free fatty acids, fatty acid esters of hydroxy fatty acids and phospholipids clearly reflecting the dysregulation of lipid metabolism upon exposure to mycotoxin and/or silymarin. Full article
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Article
Determination of Butyrate Synthesis Capacity in Gut Microbiota: Quantification of but Gene Abundance by qPCR in Fecal Samples
Biomolecules 2021, 11(9), 1303; https://doi.org/10.3390/biom11091303 - 02 Sep 2021
Cited by 1 | Viewed by 671
Abstract
Butyrate is formed in the gut during bacterial fermentation of dietary fiber and is attributed numerous beneficial effects on the host metabolism. We aimed to develop a method for the assessment of functional capacity of gut microbiota butyrate synthesis based on the qPCR [...] Read more.
Butyrate is formed in the gut during bacterial fermentation of dietary fiber and is attributed numerous beneficial effects on the host metabolism. We aimed to develop a method for the assessment of functional capacity of gut microbiota butyrate synthesis based on the qPCR quantification of bacterial gene coding butyryl-CoA:acetate CoA-transferase, the key enzyme of butyrate synthesis. In silico, we identified bacteria possessing but gene among human gut microbiota by searching but coding sequences in available databases. We designed and validated six sets of degenerate primers covering all selected bacteria, based on their phylogenetic nearness and sequence similarity, and developed a method for gene abundance normalization in human fecal DNA. We determined but gene abundance in fecal DNA of subjects with opposing dietary patterns and metabolic phenotypes—lean vegans (VG) and healthy obese omnivores (OB) with known fecal microbiota and metabolome composition. We found higher but gene copy number in VG compared with OB, in line with higher fecal butyrate content in VG group. We further found a positive correlation between the relative abundance of target bacterial genera identified by next-generation sequencing and groups of but gene-containing bacteria determined by specific primers. In conclusion, this approach represents a simple and feasible tool for estimation of microbial functional capacity. Full article
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Review

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Review
Fecal Microbial Transplantation in Critically Ill Patients—Structured Review and Perspectives
Biomolecules 2021, 11(10), 1459; https://doi.org/10.3390/biom11101459 - 04 Oct 2021
Cited by 1 | Viewed by 687
Abstract
The human gut microbiota consists of bacteria, archaea, fungi, and viruses. It is a dynamic ecosystem shaped by several factors that play an essential role in both healthy and diseased states of humans. A disturbance of the gut microbiota, also termed “dysbiosis”, is [...] Read more.
The human gut microbiota consists of bacteria, archaea, fungi, and viruses. It is a dynamic ecosystem shaped by several factors that play an essential role in both healthy and diseased states of humans. A disturbance of the gut microbiota, also termed “dysbiosis”, is associated with increased host susceptibility to a range of diseases. Because of splanchnic ischemia, exposure to antibiotics, and/or the underlying disease, critically ill patients loose 90% of the commensal organisms in their gut within hours after the insult. This is followed by a rapid overgrowth of potentially pathogenic and pro-inflammatory bacteria that alter metabolic, immune, and even neurocognitive functions and that turn the gut into the driver of systemic inflammation and multiorgan failure. Indeed, restoring healthy microbiota by means of fecal microbiota transplantation (FMT) in the critically ill is an attractive and plausible concept in intensive care. Nonetheless, available data from controlled studies are limited to probiotics and FMT for severe C. difficile infection or severe inflammatory bowel disease. Case series and observational trials have generated hypotheses that FMT might be feasible and safe in immunocompromised patients, refractory sepsis, or severe antibiotic-associated diarrhea in ICU. There is a burning need to test these hypotheses in randomized controlled trials powered for the determination of patient-centered outcomes. Full article
Review
Gut Microbiota as the Link between Elevated BCAA Serum Levels and Insulin Resistance
Biomolecules 2021, 11(10), 1414; https://doi.org/10.3390/biom11101414 - 28 Sep 2021
Cited by 1 | Viewed by 680
Abstract
The microbiota-harboring human gut is an exquisitely active ecosystem that has evolved in a constant symbiosis with the human host. It produces numerous compounds depending on its metabolic capacity and substrates availability. Diet is the major source of the substrates that are metabolized [...] Read more.
The microbiota-harboring human gut is an exquisitely active ecosystem that has evolved in a constant symbiosis with the human host. It produces numerous compounds depending on its metabolic capacity and substrates availability. Diet is the major source of the substrates that are metabolized to end-products, further serving as signal molecules in the microbiota-host cross-talk. Among these signal molecules, branched-chain amino acids (BCAAs) has gained significant scientific attention. BCAAs are abundant in animal-based dietary sources; they are both produced and degraded by gut microbiota and the host circulating levels are associated with the risk of type 2 diabetes. This review aims to summarize the current knowledge on the complex relationship between gut microbiota and its functional capacity to handle BCAAs as well as the host BCAA metabolism in insulin resistance development. Targeting gut microbiota BCAA metabolism with a dietary modulation could represent a promising approach in the prevention and treatment of insulin resistance related states, such as obesity and diabetes. Full article
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: Untargeted metabolomics approach reveals new secondary bile acid conversion by the human gut microbiota
Authors: Garcia, CJ; Kosek, V; Beltran, D; Hajslova, J; Tomas-Barberán, FA
Affiliation: University of Chemistry and Technology, Prague, Czech Republic
Abstract: The Biles acids are endogenous acidic steroids with amphiphilic behavior synthetized in the hepatocyte. The Biles acids carry out important function as fat absorption but they are also signaling molecules and metabolic regulators that activate nuclear receptor and G protein-coupled receptor signaling to regulated hepatic lipid, glucose and maintain the metabolic homeostasis. The primary bile acids are converted to the secondary bile acids by the gut microbiota. The secondary bile acids are dehydroxylated and oxidized derivates produced by 7α-dehydroxylase and hydroxysteroid dehydrogenase respectively. In this study, fecal samples from different donors, previously classified by metabotypes according of their gut microbiota production of urolithins, were evaluated to described the secondary bile acid production by the human gut microbiota. Untargeted metabolomics techniques revealed new conversion of secondary Biles acids produced by the gut microbiota. The new metabolites identified were classified into oxidized secondary bile acids. The results also showed that the gut microbiota can reduced the double bond of this new oxidized metabolites to convert back them into the original dehydroxylated. This research opens a new perspective regarding of the microbe’s population trends of created a more oxidized or reduced Biles acid environmental and its repercussion.

Title: Fecal Microbial Transplantation in Critically Ill Patients - Narrative Review and Perspectives
Authors: Cibulková, Ivana
Affiliation: Charles University - Univerzita Karlova, Prague, Czech Republic
Abstract: The human gut microbiota represents a complex ecosystem of bacteria, archaea, fungi and viruses. It is a dynamic ecosystem shaped by a number of factors, which play an essential role in both healthy and diseased states of humans. It has been demonstrated that a condition of disturbance of the gut microbiota, also termed “dysbiosis,” can influence host susceptibility to many disorders, although a direct causality is not completely proven. It is described that the conditions of critical illness influence gut microbiome and 90% of the commensal organisms in gut are lost within the first six hours of the insult of critical illness followed by overgrowth of potentially pathogenic and inflammatory bacteria. Some microbiome studies of ICU patients suggest that the gut could be a driver of sepsis and multiorgan failure and gut dysbiosis could lead to metabolic, immune, and even neurocognitive disturbances for the critically ill patient. Nowadays microbiota-targeted interventions as prebiotics, probiotics, and fecal microbiota transplantation (FMT) is widely discussed as a novel treatment options in many indications. Recent clinical data indicate that probiotics and FMT are promising therapies in ICU patients especially for severe C. difficile infection (CDI) or severe inflammatory bowel disease (IBD). Limited data available shows that FMT could be successfully used also in the treatment of therapy-resistant sepsis and severe diarrhea on ICU. In our review, we aim to describe the available knowledge about the role of the microbiome in critical illness and how microbiome-related therapy, specifically FBT, could be used in ICU clinical practice.

Title: Simple method for the determination of functional capacity of gut microbiota: quantification of selected genes by RT-qPCR
Authors: Nikola Daskova; Marie Heczkova; Istvan Modos; Petra Videnska; Petra Splichalova; Helena Pelantova; Marek Kuzma; Jan Gojda; Monika Cahova
Affiliation: Institutu Klinické a Experimentální Medicíny, Prague, Czech Republic; Centre for Research on Diabetes, Metabolism and Nutrition, Charles University in Prague, Prague, Czech Republic
Abstract: Butyrate is formed in the gut during bacterial fermentation of dietary fiber and is attributed numerous beneficial effects on the host metabolism. We aimed to develop a simple method for the assessment of functional capacity of gut microbiota butyrate synthesis based on the RT-qPCR quantification of bacterial butyryl-CoA:acetate CoA-transferase, the key enzyme of butyrate synthesis. In silico, we identified bacteria possessing but gene among human gut microbiota by searching but coding sequences in available databases. We designed and validated six sets of degenerate primers covering all selected bacteria, based on their phylogenetic nearness and sequence similarity, and developed a method for gene expression normalization in human fecal DNA. We determined but expression in fecal DNA of subjects with opposing dietary patterns and metabolic phenotypes – vegans (VG) and healthy obese omnivores (OB) with known fecal microbiota and metabolome composition. We found higher but expression in VG compared with OB, in line with higher fecal butyrate content in VG group. We further found positive correlation between the abundance of target bacterial genera identified by next-generation sequencing and groups of but gene-containing bacteria determined by specific primers. In conclusion, this approach represents simple and feasible tool for estimation of microbial functional capacity.

Title: Antibiotic support of subgingival therapy affects the oral microbiome of periodontitis patients positively and remarkably, but only temporarily
Authors: Jiri Janata; Lucie Najmanová
Affiliation: Academy of Sciences of the Czech Republic, Prague, Czech Republic
Abstract: Periodontitis is one of the most frequent diseases in the developed world. Just recently, it has been reconsidered to belong rather to non-communicable chronic diseases then infectious diseases, nevertheless, the oral microbiome dysbiosis plays a key role in its pathogenesis. In this study, we employed NGS methods to compare the oral microbiome composition dynamics for two approved types of periodontitis treatment differing in the administration of antibiotics. A set of 53 patients with a severe (formerly aggressive) periodontitis was randomly divided into two groups, both treated by deep scaling and root planning (SRP), but only one treated additionally with antibiotics. The course of treatment was monitored before the intervention (T0), after two weeks (T1) and after two months (T2). A set of clinically relevant parameters was evaluated (a number of affected teeth; PPD, the periodontal pocket depth; BOP, bleeding on probing and CAL, clinical attachment loss) as well as the composition of the oral bacterial microflora in samples taken from the deepest periodontal pocket. All clinical parameters improved similarly in time in both observed groups, however, the response reflected in the taxonomic composition of oral microbiota statistically differed in time T1. The shift in the overall taxonomic composition expressed by R/G index, as well as the shift in the representation of main groups of periopathogenic bacteria (red complex, Fretibacteria) towards the values typical for periodontally healthy individuals was remarkably bigger in samples from patients treated by SRP + antibiotics. Nevertheless, this difference between groups was statistically significant only in the time T1 (shortly after antibiotic treatment) and later it slowly decreased. Forty-three patients were sampled once more after 18 months (T3) and in this time the microbial composition analysis did not reveal any difference between groups. This study showed that the NGS methods meaningfully complement the clinical examination of patients with periodontitis and provide a deeper insight in the process of healing. The obtained results also revealed the potential of systemically administered antibiotics to temporarily shift the oral microbiome composition. This short period of dramatic improvement gives us the opportunity to apply some further tools like probiotics to keep the positive trend.

Title: NMR-based metabolomic approach for evaluation of the role of gut microbiota in mice experimental model of DSS-induced colitis
Authors: Anastazia Nazmutdinova; Marek Kuzma
Affiliation: Institute of Microbiology, Czech Academy of Science, Prague, Czech Republic
Abstract: Gut microbiota plays a significant role in developing inflammatory bowel diseases such as Crohn’s disease and ulcerative colitis. Dysbiosis is one of the inherent symptoms of these diseases, which can cause an alteration of the normal balance of metabolites and lead to an aberrant immune response of the host’s gut mucosa. Untargeted NMR metabolomics is now one of the most important tools to follow metabolomic changes cause by diseases and evaluate suspected biomarkers of diseases. The aim was to compare the development of intestinal inflammation in normal and germ-free mice in experimental DSS-induced colitis. It was evaluated their fecal, urine, and serum metabolomic profiles by NMR to help understand the microbiome contribution to gut function and follow metabolic changes caused by inflammation.

Title: Effect of high-fat diet on the composition of the intestinal metabolome in a mouse model of tau pathology of Alzheimer disease
Authors: T.T.R. Nguyen; Marek Kuzma
Affiliation: Institute of Microbiology, Czech Academy of Science, Prague, Czech Republic
Abstract: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the presence of senile plaques (amyloid beta - Aß aggregates); and neurofibrillary tangles (aggregated Tau protein). The hypothesis of the amyloid cascade was studied for a long time. Nowadays, the inflammatory-infectious AD hypothesis with the role of the intestinal microbiome is getting more attention. Gut bacteria can have a significant impact on the immune system, brain development, and behavior. Obesity and metabolic disorders can be risk factors for the onset and development of neurodegenerative diseases. A high-fat diet can cause dysbiosis (imbalance in the gut microbiome), which can lead to the development of local and systemic inflammation or dysregulation of the intestinal-brain axis. This study is focused on the experimental model THY-Tau22, a unique mouse model in which neurodegeneration develops exclusively through the emergence of tau pathology. Therefore, we focused on the comparison of the intestinal microbiome; and fecal and urine metabolome caused by obesity and tau pathology.

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