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Special Issue "Gut Microbes and Gut Metabolites"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: closed (30 April 2021).

Special Issue Editor

Dr. Gwenaelle Le Gall
E-Mail Website
Guest Editor
Norwich Medical School at UEA, UK
Interests: metabolomics; lipidomics; gut metabolites; health; nutrition; metabolism; dietary phytochemicals; bioactive compounds; microbiota

Special Issue Information

Dear Colleagues,

The scope of this special issue is to compile a series of original research papers and reviews that demonstrate a link between dietary metabolite products* and an improvement in human health indicators.

Interventions can provide microbes (probiotics) or foods/ supplements with components such as flavonoids, phenolic compounds or non-digestible carbohydrates (prebiotics) in the diet with the aim of  effecting positive changes in the gut microbiota. Several general mechanisms have been established by which the gut bacteria or their major products (short chain fatty acids) can affect aspects of the host’s biology including the immune system, gut barrier function and energy metabolism. However, the mechanisms by which specific probiotics or prebiotics act are much less established.

Some of the microbial metabolite products - degradation products of polyphenols, complex carbohydrates, dietary protein and amino acids - and endogenous metabolites related to energy pathways (Krebs cycle, glycolysis, beta-oxidation) and those involved in digestion (bile acids) have the capacity to interact with the microbiome, leading potentially to a net positive balance in health or at least to a sustainable homeostasis.

In vivo and in vitro studies on host metabolism (lipid and energy pathways) and involvement of microbiota will be particularly welcome.

This special issue will offer experts in the field the opportunity to display the latest results in nutritional metabolomics/lipidomics and review the current developments while providing the readers with an exciting prospect of new possibilities in preventive medicine and precision nutrition research.

* phenolic compounds, short chain fatty acids, biogenic amines, etc.

Dr. Gwenaelle Le Gall
Guest Editor

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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 metabolites
  • metabolism
  • phenolic compounds
  • short chain fatty acids
  • metabolomics
  • lipidomics
  • prebiotics
  • probiotics
  • microbiota
  • health
  • nutrition

Published Papers (10 papers)

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Research

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Open AccessArticle
A Newly Developed Synbiotic Yogurt Prevents Diabetes by Improving the Microbiome–Intestine–Pancreas Axis
Int. J. Mol. Sci. 2021, 22(4), 1647; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22041647 - 06 Feb 2021
Viewed by 1183
Abstract
The prevalence of type 2 diabetes mellitus (T2D) is increasing worldwide, and there are no long-term preventive strategies to stop this growth. Emerging research shows that perturbations in the gut microbiome significantly contribute to the development of T2D, while microbiome modulators may be [...] Read more.
The prevalence of type 2 diabetes mellitus (T2D) is increasing worldwide, and there are no long-term preventive strategies to stop this growth. Emerging research shows that perturbations in the gut microbiome significantly contribute to the development of T2D, while microbiome modulators may be beneficial for T2D prevention. However, microbiome modulators that are effective, safe, affordable, and able to be administered daily are not yet available. Based on our previous pro- and prebiotic studies, we developed a novel synbiotic yogurt comprised of human-origin probiotics and plant-based prebiotics and investigated its impact on diet- and streptozotocin-induced T2D in mice. We compared the effects of our synbiotic yogurt to those of a commercially available yogurt (control yogurt). Interestingly, we found that the feeding of the synbiotic yogurt significantly reduced the development of hyperglycemia (diabetes) in response to high-fat diet feeding and streptozotocin compared to milk-fed controls. Surprisingly, the control yogurt exacerbated diabetes progression. Synbiotic yogurt beneficially modulated the gut microbiota composition compared to milk, while the control yogurt negatively modulated it by significantly increasing the abundance of detrimental bacteria such as Proteobacteria and Enterobacteriaceae. In addition, the synbiotic yogurt protected pancreatic islet morphology compared to the milk control, while the control yogurt demonstrated worse effects on islets. These results suggest that our newly developed synbiotic yogurt protects against diabetes in mice and can be used as a therapeutic to prevent diabetes progression. Full article
(This article belongs to the Special Issue Gut Microbes and Gut Metabolites)
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Open AccessArticle
The Associations of SCFA with Anthropometric Parameters and Carbohydrate Metabolism in Pregnant Women
Int. J. Mol. Sci. 2020, 21(23), 9212; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21239212 - 03 Dec 2020
Cited by 1 | Viewed by 564
Abstract
Short-chain fatty acids (SCFAs) mediate the transmission of signals between the microbiome and the immune system and are responsible for maintaining balance in the anti-inflammatory reaction. Pregnancy stages alter the gut microbiota community structure, which also synthesizes SCFAs. The study involved 90 pregnant [...] Read more.
Short-chain fatty acids (SCFAs) mediate the transmission of signals between the microbiome and the immune system and are responsible for maintaining balance in the anti-inflammatory reaction. Pregnancy stages alter the gut microbiota community structure, which also synthesizes SCFAs. The study involved 90 pregnant women, divided into two groups: 48 overweight/obese pregnant women (OW) and 42 pregnant women with normal BMI (CG). The blood samples for glucose, insulin, and HBA1c were analyzed as well as stool samples for SCFA isolation (C2:0; C3:0; C4:0i; C4:0n; C5:0i; C5:0n; C6:0i; C6:0n) using gas chromatography. The SCFA profile in the analyzed groups differed significantly. A significant positive correlation between C2:0, C3:0, C4:0n and anthropometric measurements, and between C2:0, C3:0, C4:0n, and C5:0n and parameters of carbohydrate metabolism was found. SCFA levels fluctuate during pregnancy and the course of pregnancy and participate in the change in carbohydrate metabolism as well. The influence of C2:0 during pregnancy on anthropometric parameters was visible in both groups (normal weight and obese). Butyrate and propionate regulate glucose metabolism by stimulating the process of intestinal gluconeogenesis. The level of propionic acid decreases with the course of pregnancy, while its increase is characteristic of obese women, which is associated with many metabolic adaptations. Propionic and linear caproic acid levels can be an important critical point in maintaining lower anthropometric parameters during pregnancy. Full article
(This article belongs to the Special Issue Gut Microbes and Gut Metabolites)
Open AccessArticle
Targeting on Gut Microbiota-Derived Metabolite Trimethylamine to Protect Adult Male Rat Offspring against Hypertension Programmed by Combined Maternal High-Fructose Intake and Dioxin Exposure
Int. J. Mol. Sci. 2020, 21(15), 5488; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21155488 - 31 Jul 2020
Cited by 4 | Viewed by 862
Abstract
Gut microbiota-dependent metabolites, in particular trimethylamine (TMA), are linked to hypertension. Maternal 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure or consumption of food high in fructose (HFR) can induce hypertension in adult offspring. We examined whether 3,3-maternal dimethyl-1-butanol (DMB, an inhibitor of TMA formation) therapy can protect [...] Read more.
Gut microbiota-dependent metabolites, in particular trimethylamine (TMA), are linked to hypertension. Maternal 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure or consumption of food high in fructose (HFR) can induce hypertension in adult offspring. We examined whether 3,3-maternal dimethyl-1-butanol (DMB, an inhibitor of TMA formation) therapy can protect adult offspring against hypertension arising from combined HFR and TCDD exposure. Pregnant Sprague–Dawley rats received regular chow or chow supplemented with fructose (60% diet by weight) throughout pregnancy and lactation. Additionally, the pregnant dams received TCDD (200 ng/kg BW orally) or a corn oil vehicle on days 14 and 21 of gestation, and days 7 and 14 after birth. Some mother rats received 1% DMB in their drinking water throughout pregnancy and lactation. Six groups of male offspring were studied (n = 8 for each group): regular chow (CV), high-fructose diet (HFR), regular diet+TCDD exposure (CT), HFR+TCDD exposure (HRT), high-fructose diet+DMB treatment (HRD), and HFR+TCDD+DMB treatment (HRTD). Our data showed that TCDD exacerbates HFR-induced elevation of blood pressure in male adult offspring, which was prevented by maternal DMB administration. We observed that different maternal insults induced distinct enterotypes in adult offspring. The beneficial effects of DMB are related to alterations of gut microbiota, the increase in nitric oxide (NO) bioavailability, the balance of the renin-angiotensin system, and antagonization of aryl hydrocarbon receptor (AHR) signaling. Our findings cast new light on the role of early intervention targeting of the gut microbiota-dependent metabolite TMA, which may allow us to prevent the development of hypertension programmed by maternal excessive fructose intake and environmental dioxin exposure. Full article
(This article belongs to the Special Issue Gut Microbes and Gut Metabolites)
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Review

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Open AccessReview
Comparative Analysis of the Microbiome across the Gut–Skin Axis in Atopic Dermatitis
Int. J. Mol. Sci. 2021, 22(8), 4228; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22084228 - 19 Apr 2021
Viewed by 250
Abstract
Atopic dermatitis (AD) is a refractory and relapsing skin disease with a complex and multifactorial etiology. Various congenital malformations and environmental factors are thought to be involved in the onset of the disease. The etiology of the disease has been investigated, with respect [...] Read more.
Atopic dermatitis (AD) is a refractory and relapsing skin disease with a complex and multifactorial etiology. Various congenital malformations and environmental factors are thought to be involved in the onset of the disease. The etiology of the disease has been investigated, with respect to clinical skin symptoms and systemic immune response factors. A gut microbiome–mediated connection between emotional disorders such as depression and anxiety, and dermatologic conditions such as acne, based on the comorbidities of these two seemingly unrelated disorders, has long been hypothesized. Many aspects of this gut–brain–skin integration theory have recently been revalidated to identify treatment options for AD with the recent advances in metagenomic analysis involving powerful sequencing techniques and bioinformatics that overcome the need for isolation and cultivation of individual microbial strains from the skin or gut. Comparative analysis of microbial clusters across the gut–skin axis can provide new information regarding AD research. Herein, we provide a historical perspective on the modern investigation and clinical implications of gut–skin connections in AD in terms of the integration between the two microbial clusters. Full article
(This article belongs to the Special Issue Gut Microbes and Gut Metabolites)
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Open AccessReview
The Multiomics Analyses of Fecal Matrix and Its Significance to Coeliac Disease Gut Profiling
Int. J. Mol. Sci. 2021, 22(4), 1965; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22041965 - 17 Feb 2021
Cited by 1 | Viewed by 611
Abstract
Gastrointestinal (GIT) diseases have risen globally in recent years, and early detection of the host’s gut microbiota, typically through fecal material, has become a crucial component for rapid diagnosis of such diseases. Human fecal material is a complex substance composed of undigested macromolecules [...] Read more.
Gastrointestinal (GIT) diseases have risen globally in recent years, and early detection of the host’s gut microbiota, typically through fecal material, has become a crucial component for rapid diagnosis of such diseases. Human fecal material is a complex substance composed of undigested macromolecules and particles, and the processing of such matter is a challenge due to the unstable nature of its products and the complexity of the matrix. The identification of these products can be used as an indication for present and future diseases; however, many researchers focus on one variable or marker looking for specific biomarkers of disease. Therefore, the combination of genomics, transcriptomics, proteomics and metabonomics can give a detailed and complete insight into the gut environment. The proper sample collection, sample preparation and accurate analytical methods play a crucial role in generating precise microbial data and hypotheses in gut microbiome research, as well as multivariate data analysis in determining the gut microbiome functionality in regard to diseases. This review summarizes fecal sample protocols involved in profiling coeliac disease. Full article
(This article belongs to the Special Issue Gut Microbes and Gut Metabolites)
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Open AccessReview
Nanoparticles in the Food Industry and Their Impact on Human Gut Microbiome and Diseases
Int. J. Mol. Sci. 2021, 22(4), 1942; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22041942 - 16 Feb 2021
Viewed by 834
Abstract
The use of inorganic nanoparticles (NPs) has expanded into various industries including food manufacturing, agriculture, cosmetics, and construction. This has allowed NPs access to the human gastrointestinal tract, yet little is known about how they may impact human health. As the gut microbiome [...] Read more.
The use of inorganic nanoparticles (NPs) has expanded into various industries including food manufacturing, agriculture, cosmetics, and construction. This has allowed NPs access to the human gastrointestinal tract, yet little is known about how they may impact human health. As the gut microbiome continues to be increasingly implicated in various diseases of unknown etiology, researchers have begun studying the potentially toxic effects of these NPs on the gut microbiome. Unfortunately, conflicting results have limited researcher’s ability to evaluate the true impact of NPs on the gut microbiome in relation to health. This review focuses on the impact of five inorganic NPs (silver, iron oxide, zinc oxide, titanium dioxide, and silicon dioxide) on the gut microbiome and gastrointestinal tract with consideration for various methodological differences within the literature. This is important as NP-induced changes to the gut could lead to various gut-related diseases. These include irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), celiac disease, and colorectal cancer. Research in this area is necessary as the use of NPs in various industries continues to grow along with the number of people suffering from chronic gastrointestinal diseases. Full article
(This article belongs to the Special Issue Gut Microbes and Gut Metabolites)
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Open AccessReview
Recent Advances of Microbiome-Associated Metabolomics Profiling in Liver Disease: Principles, Mechanisms, and Applications
Int. J. Mol. Sci. 2021, 22(3), 1160; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031160 - 25 Jan 2021
Viewed by 653
Abstract
Advances in high-throughput screening of metabolic stability in liver and gut microbiota are able to identify and quantify small-molecule metabolites (metabolome) in different cellular microenvironments that are closest to their phenotypes. Metagenomics and metabolomics are largely recognized to be the “-omics” disciplines for [...] Read more.
Advances in high-throughput screening of metabolic stability in liver and gut microbiota are able to identify and quantify small-molecule metabolites (metabolome) in different cellular microenvironments that are closest to their phenotypes. Metagenomics and metabolomics are largely recognized to be the “-omics” disciplines for clinical therapeutic screening. Here, metabolomics activity screening in liver disease (LD) and gut microbiomes has significantly delivered the integration of metabolomics data (i.e., a set of endogenous metabolites) with metabolic pathways in cellular environments that can be tested for biological functions (i.e., phenotypes). A growing literature in LD and gut microbiomes reports the use of metabolites as therapeutic targets or biomarkers. Although growing evidence connects liver fibrosis, cirrhosis, and hepatocellular carcinoma, the genetic and metabolic factors are still mainly unknown. Herein, we reviewed proof-of-concept mechanisms for metabolomics-based LD and gut microbiotas’ role from several studies (nuclear magnetic resonance, gas/lipid chromatography, spectroscopy coupled with mass spectrometry, and capillary electrophoresis). A deeper understanding of these axes is a prerequisite for optimizing therapeutic strategies to improve liver health. Full article
(This article belongs to the Special Issue Gut Microbes and Gut Metabolites)
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Open AccessReview
Effects of Gut Metabolites and Microbiota in Healthy and Marginal Livers Submitted to Surgery
Int. J. Mol. Sci. 2021, 22(1), 44; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010044 - 22 Dec 2020
Cited by 1 | Viewed by 692
Abstract
Microbiota is defined as the collection of microorganisms within the gastrointestinal ecosystem. These microbes are strongly implicated in the stimulation of immune responses. An unbalanced microbiota, termed dysbiosis, is related to the development of several liver diseases. The bidirectional relationship between the gut, [...] Read more.
Microbiota is defined as the collection of microorganisms within the gastrointestinal ecosystem. These microbes are strongly implicated in the stimulation of immune responses. An unbalanced microbiota, termed dysbiosis, is related to the development of several liver diseases. The bidirectional relationship between the gut, its microbiota and the liver is referred to as the gut–liver axis. The translocation of bacterial products from the intestine to the liver induces inflammation in different cell types such as Kupffer cells, and a fibrotic response in hepatic stellate cells, resulting in deleterious effects on hepatocytes. Moreover, ischemia-reperfusion injury, a consequence of liver surgery, alters the microbiota profile, affecting inflammation, the immune response and even liver regeneration. Microbiota also seems to play an important role in post-operative outcomes (i.e., liver transplantation or liver resection). Nonetheless, studies to determine changes in the gut microbial populations produced during and after surgery, and affecting liver function and regeneration are scarce. In the present review we analyze and discuss the preclinical and clinical studies reported in the literature focused on the evaluation of alterations in microbiota and its products as well as their effects on post-operative outcomes in hepatic surgery. Full article
(This article belongs to the Special Issue Gut Microbes and Gut Metabolites)
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Open AccessReview
Leaky Gut and Autoimmunity: An Intricate Balance in Individuals Health and the Diseased State
Int. J. Mol. Sci. 2020, 21(24), 9770; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21249770 - 21 Dec 2020
Cited by 1 | Viewed by 1412
Abstract
Damage to the tissue and the ruining of functions characterize autoimmune syndromes. This review centers around leaky gut syndromes and how they stimulate autoimmune pathogenesis. Lymphoid tissue commonly associated with the gut, together with the neuroendocrine network, collaborates with the intestinal epithelial wall, [...] Read more.
Damage to the tissue and the ruining of functions characterize autoimmune syndromes. This review centers around leaky gut syndromes and how they stimulate autoimmune pathogenesis. Lymphoid tissue commonly associated with the gut, together with the neuroendocrine network, collaborates with the intestinal epithelial wall, with its paracellular tight junctions, to maintain the balance, tolerance, and resistance to foreign/neo-antigens. The physiological regulator of paracellular tight junctions plays a vital role in transferring macromolecules across the intestinal barrier and thereby maintains immune response equilibrium. A new paradigm has explained the intricacies of disease development and proposed that the processes can be prevented if the interaction between the genetic factor and environmental causes is barred by re-instituting the intestinal wall function. The latest clinical evidence and animal models reinforce this current thought and offer the basis for innovative methodologies to thwart and treat autoimmune syndromes. Full article
(This article belongs to the Special Issue Gut Microbes and Gut Metabolites)
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Open AccessReview
The Role of Short-Chain Fatty Acids in the Interplay between a Very Low-Calorie Ketogenic Diet and the Infant Gut Microbiota and Its Therapeutic Implications for Reducing Asthma
Int. J. Mol. Sci. 2020, 21(24), 9580; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21249580 - 16 Dec 2020
Viewed by 814
Abstract
Gut microbiota is well known as playing a critical role in inflammation and asthma development. The very low-calorie ketogenic diet (VLCKD) is suggested to affect gut microbiota; however, the effects of VLCKD during pregnancy and lactation on the infant gut microbiota are unclear. [...] Read more.
Gut microbiota is well known as playing a critical role in inflammation and asthma development. The very low-calorie ketogenic diet (VLCKD) is suggested to affect gut microbiota; however, the effects of VLCKD during pregnancy and lactation on the infant gut microbiota are unclear. The VLCKD appears to be more effective than caloric/energy restriction diets for the treatment of several diseases, such as obesity and diabetes. However, whether adherence to VLCKD affects the infant gut microbiota and the protective effects thereof on asthma remains uncertain. The exact mechanisms underlying this process, and in particular the potential role of short chain fatty acids (SCFAs), are still to be unravelled. Thus, the aim of this review is to identify the potential role of SCFAs that underlie the effects of VLCKD during pregnancy and lactation on the infant gut microbiota, and explore whether it incurs significant implications for reducing asthma. Full article
(This article belongs to the Special Issue Gut Microbes and Gut Metabolites)
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