Current Status of Research on Gut Metabolites and Microbiota

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Collection Editor
Department of Microbiology, Ramón y Cajal Institute for Health Research (IRYCIS), Ramón y Cajal University Hospital, 28034 Madrid, Spain
Interests: microbial ecology; infectious diseases; human microbiome; microbial interactions; antibiotic resistance; omics
Special Issues, Collections and Topics in MDPI journals

Topical Collection Information

Dear Colleagues,

Metabolites are small molecules that derive from cell metabolism. In the last few years, the role of metabolites produced in the gut by the microbiome–host system has attracted much attention. They can be considered to be “molecular words” in the communication language within the gut microbial community (microbe–microbe) and other microbial communities in the body, such as those inhabiting the skin, the oral cavity, or the respiratory tract, as well as to and from the host (microbe–host). Metabolites circulating in the gut are involved in several host physiological processes, such as nutrition, immune system stimulation, epithelium maintenance, and colonization resistance. Interruption of the metabolite-based dialogue between the microbiota and the host leads to disease, not only intestinal but affecting other organs or systemic. It is the case for intestinal inflammatory bowel disease, Clostridium difficile colitis, colorectal cancer, asthma, and some metabolic, neurological, reproductive, and immune-system-associated disorders where the gut metabolome (the complete set of small molecules from the gut) plays a part in their outcome. Omics approaches, especially metagenomics combined with metabolomics, have significantly contributed to the study of the function of critical metabolites for health, such as short-chain fatty acids, bile acids, amino acids, and polyamines and to the identification of their producers. However, our knowledge of the ecological web of metabolic interactions is filled with gaps due to the ecological complexity of the gut microbiome–host interplay. The area of microbiome metabolomics is promising and already expanding, especially regarding its therapeutic applications. We thus invite contributions to this Topic Collection in the form of original research articles, case reports, short communications, or review papers that cover any aspect of gut metabolites and the microbiome, and host–microbiome interplay, including new research, new data, novel methodologies, and future perspectives.

Dr. Ana Elena Pérez Cobas
Collection Editor

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Keywords

  • gut
  • microbiota
  • metabolites
  • metabolomics
  • interaction
  • physiology

Published Papers (11 papers)

2022

Jump to: 2021

11 pages, 635 KiB  
Review
Effect of Probiotics on Host-Microbiota in Bacterial Infections
by Ascensión Rueda-Robles, Avilene Rodríguez-Lara, Matthew S. Meyers, María José Sáez-Lara and Ana I. Álvarez-Mercado
Pathogens 2022, 11(9), 986; https://doi.org/10.3390/pathogens11090986 - 29 Aug 2022
Cited by 9 | Viewed by 2613
Abstract
Diseases caused by bacteria cause millions of deaths every year. In addition, the problem of resistance to antibiotics is so serious that it threatens the achievements of modern medicine. This is a very important global problem as some bacteria can also develop persistence. [...] Read more.
Diseases caused by bacteria cause millions of deaths every year. In addition, the problem of resistance to antibiotics is so serious that it threatens the achievements of modern medicine. This is a very important global problem as some bacteria can also develop persistence. Indeed, the persistence of pathogenic bacteria has evolved as a potent survival strategy to overcome host organisms’ defense mechanisms. Additionally, chronic or persistent infections may be caused by persisters which could facilitate antibiotic resistance. Probiotics are considered good bacteria. It has been described that the modulation of gut microbiota by probiotics could have a great potential to counteract the deleterious impact and/or regulate gut microbiota after bacterial infection. Probiotics might provide health benefits through the inhibition of pathogen growth or the replacement of pathogenic bacteria. Bearing in mind that current strategies to avoid bacterial persistence and prevent antibiotic resistance are not effective, other strategies need to be assessed. We have carried out a comprehensive review, which included the reported literature between 2016 and 2021, highlighting the clinical trials that reported the probiotics’ potential to regulate gut microbiota after bacterial infection and focusing in particular on the context of antibiotic resistance and persister cells. Full article
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8 pages, 272 KiB  
Case Report
Bacteraemia Caused by Probiotic Strains of Lacticaseibacillus rhamnosus—Case Studies Highlighting the Need for Careful Thought before Using Microbes for Health Benefits
by Agnieszka Mikucka, Aleksander Deptuła, Tomasz Bogiel, Agnieszka Chmielarczyk, Elżbieta Nurczyńska and Eugenia Gospodarek-Komkowska
Pathogens 2022, 11(9), 977; https://doi.org/10.3390/pathogens11090977 - 26 Aug 2022
Cited by 9 | Viewed by 2463
Abstract
Lactic acid bacteria belonging to Lactobacillus spp. and Lacticaseibacillus spp. are a natural part of fermented milk and other food products, probiotic supplements and human microbiota. They mainly belong to mucosal microflora, especially oral, vaginal and intestinal. Lacticaseibacillus spp. strains included in probiotics [...] Read more.
Lactic acid bacteria belonging to Lactobacillus spp. and Lacticaseibacillus spp. are a natural part of fermented milk and other food products, probiotic supplements and human microbiota. They mainly belong to mucosal microflora, especially oral, vaginal and intestinal. Lacticaseibacillus spp. strains included in probiotics are generally characterised as safe microorganisms, and the species are concerned bacteria with very low pathogenic potential. However, infections caused by Lactobacillus spp. and Lacticaseibacillus spp., including bacteraemia and endocarditis, occur occasionally. The aim of the study was to present two cases of bacteraemia due to Lacticaseibacillus rhamnosus associated with the use of a probiotic product. It afflicted patients in intensive care units. The investigation was preliminarily based on clinical and microbiological recognition of the cases. The initial observation was laboratory confirmed with the application of pulsed-field gel electrophoresis (PFGE) results. Identical PFGE patterns were obtained for the evaluated strains and the strains derived from a commercially available probiotic that was administered to those patients. The increasing number of studies describing opportunistic infections due to probiotic strains of Lacticaseibacillus spp. should result in verifying the safety of probiotic formulations used in immunocompromised patients and forming detailed guidelines for the use of probiotics among patients from several risk groups. Full article
13 pages, 2927 KiB  
Article
An Investigation of the Effect of Water Additives on Broiler Growth and the Caecal Microbiota at Harvest
by Genevieve Greene, Leonard Koolman, Paul Whyte, Catherine M. Burgess, Helen Lynch, Aidan Coffey, Brigid Lucey, Lisa O’Connor and Declan Bolton
Pathogens 2022, 11(8), 932; https://doi.org/10.3390/pathogens11080932 - 18 Aug 2022
Cited by 1 | Viewed by 1472
Abstract
Campylobacter is the most common foodborne pathogen in developed countries and most cases are associated with poultry. This study investigated the effect of three anti-Campylobacter water additives on broiler growth and on the caecal microbiota at harvest using 16S rRNA amplicon sequencing. [...] Read more.
Campylobacter is the most common foodborne pathogen in developed countries and most cases are associated with poultry. This study investigated the effect of three anti-Campylobacter water additives on broiler growth and on the caecal microbiota at harvest using 16S rRNA amplicon sequencing. Mixtures of organic acids (OA) and essential oils (EO) were administered to broilers for the entirety of the production cycle (35 d) and medium-chain fatty acids (MCFA) for 5 d immediately before harvest, under commercial conditions. Bird weight gain was significantly (p < 0.001) reduced in broilers receiving the OA and EO treatments. While this was most likely due to reduced water intake and corresponding lower feed consumption, changes to the caecal microbiota may also have contributed. Firmicutes made up over 75% of the bacteria regardless of sample type, while the minor phyla included Bacteroidetes, Actinobacteria, Melainabacteria, and Proteobacteria. There were no significant (p > 0.05) differences in the alpha diversity as measured using ACE, Chao1, and Shannon indices, except for control (water) versus MCFA and OA versus MCFA, using the Wilcox test. In contrast, there was a significant (p < 0.05) difference in beta diversity when the treated were compared to the untreated control and main flock samples, while linear discriminant analysis effect size (LeFSe) identified three OTUs that were present in the control but absent in the treated birds. It was concluded that the water additives tested adversely affected broiler performance, which may, at least in part, be due to changes in the caecal microbiota, assuming that the altered microbiota at day 35 is indicative of a change throughout the production cycle. Full article
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14 pages, 1503 KiB  
Review
Gut Microbes and Neuropathology: Is There a Causal Nexus?
by Katherine Dinan and Timothy G. Dinan
Pathogens 2022, 11(7), 796; https://doi.org/10.3390/pathogens11070796 - 14 Jul 2022
Cited by 6 | Viewed by 2924
Abstract
The gut microbiota is a virtual organ which produces a myriad of molecules that the brain and other organs require. Humans and microbes are in a symbiotic relationship, we feed the microbes, and in turn, they provide us with essential molecules. Bacteroidetes and [...] Read more.
The gut microbiota is a virtual organ which produces a myriad of molecules that the brain and other organs require. Humans and microbes are in a symbiotic relationship, we feed the microbes, and in turn, they provide us with essential molecules. Bacteroidetes and Firmicutes phyla account for around 80% of the total human gut microbiota, and approximately 1000 species of bacteria have been identified in the human gut. In adults, the main factors influencing microbiota structure are diet, exercise, stress, disease and medications. In this narrative review, we explore the involvement of the gut microbiota in Parkinson’s disease, Alzheimer’s disease, multiple sclerosis and autism, as these are such high-prevalence disorders. We focus on preclinical studies that increase the understanding of disease pathophysiology. We examine the potential for targeting the gut microbiota in the development of novel therapies and the limitations of the currently published clinical studies. We conclude that while the field shows enormous promise, further large-scale studies are required if a causal link between these disorders and gut microbes is to be definitively established. Full article
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9 pages, 274 KiB  
Review
Enterococci—Involvement in Pathogenesis and Therapeutic Potential in Cancer Treatment: A Mini-Review
by Anna Grenda, Tomasz Grenda, Piotr Domaradzki and Krzysztof Kwiatek
Pathogens 2022, 11(6), 687; https://doi.org/10.3390/pathogens11060687 - 15 Jun 2022
Cited by 3 | Viewed by 2378
Abstract
Enterococcus spp. are Gram-positive, heterogeneous lactic acid bacteria inhabiting various environments. Several species of Enterococci are considered to be able to stimulate the immune system and play an important role in intestinal homeostasis. Some Enterococci can be used as probiotics. Some strains of [...] Read more.
Enterococcus spp. are Gram-positive, heterogeneous lactic acid bacteria inhabiting various environments. Several species of Enterococci are considered to be able to stimulate the immune system and play an important role in intestinal homeostasis. Some Enterococci can be used as probiotics. Some strains of E. faecium are components of pharmaceutical products used to treat diarrhea, antibiotic-associated diarrhea, or irritable bowel syndrome (IBS). However, it has been proved that they are responsible for food contamination, and are sometimes undesirable from the point of view of food technology. Additionally, the virulence and multi-drug resistance of Enterococci potentially pose a risk of an epidemic, especially in hospital environments. Moreover, there are indications of their negative role in colon tumorigenesis; however, some nterococci are proved to support immunotherapy in cancer treatment. In general, it can be concluded that this group of microorganisms, despite its nature, has properties that can be used to support cancer treatment—both aggressive chemotherapy and cutting-edge therapy targeting immune checkpoints (IC). Full article
27 pages, 1082 KiB  
Review
Advances in Microbiome-Derived Solutions and Methodologies Are Founding a New Era in Skin Health and Care
by Audrey Gueniche, Olivier Perin, Amina Bouslimani, Leslie Landemaine, Namita Misra, Sylvie Cupferman, Luc Aguilar, Cécile Clavaud, Tarun Chopra and Ahmad Khodr
Pathogens 2022, 11(2), 121; https://doi.org/10.3390/pathogens11020121 - 20 Jan 2022
Cited by 14 | Viewed by 6637
Abstract
The microbiome, as a community of microorganisms and their structural elements, genomes, metabolites/signal molecules, has been shown to play an important role in human health, with significant beneficial applications for gut health. Skin microbiome has emerged as a new field with high potential [...] Read more.
The microbiome, as a community of microorganisms and their structural elements, genomes, metabolites/signal molecules, has been shown to play an important role in human health, with significant beneficial applications for gut health. Skin microbiome has emerged as a new field with high potential to develop disruptive solutions to manage skin health and disease. Despite an incomplete toolbox for skin microbiome analyses, much progress has been made towards functional dissection of microbiomes and host-microbiome interactions. A standardized and robust investigation of the skin microbiome is necessary to provide accurate microbial information and set the base for a successful translation of innovations in the dermo-cosmetic field. This review provides an overview of how the landscape of skin microbiome research has evolved from method development (multi-omics/data-based analytical approaches) to the discovery and development of novel microbiome-derived ingredients. Moreover, it provides a summary of the latest findings on interactions between the microbiomes (gut and skin) and skin health/disease. Solutions derived from these two paths are used to develop novel microbiome-based ingredients or solutions acting on skin homeostasis are proposed. The most promising skin and gut-derived microbiome interventional strategies are presented, along with regulatory, safety, industrial, and technical challenges related to a successful translation of these microbiome-based concepts/technologies in the dermo-cosmetic industry. Full article
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2021

Jump to: 2022

16 pages, 2263 KiB  
Article
Coffee Pulp, a By-Product of Coffee Production, Modulates Gut Microbiota and Improves Metabolic Syndrome in High-Carbohydrate, High-Fat Diet-Fed Rats
by Nikhil S. Bhandarkar, Peter Mouatt, Marwan E. Majzoub, Torsten Thomas, Lindsay Brown and Sunil K. Panchal
Pathogens 2021, 10(11), 1369; https://doi.org/10.3390/pathogens10111369 - 22 Oct 2021
Cited by 12 | Viewed by 4066
Abstract
Waste from food production can be re-purposed as raw material for usable products to decrease industrial waste. Coffee pulp is 29% of the dry weight of coffee cherries and contains caffeine, chlorogenic acid, trigonelline, diterpenes and fibre. We investigated the attenuation of signs [...] Read more.
Waste from food production can be re-purposed as raw material for usable products to decrease industrial waste. Coffee pulp is 29% of the dry weight of coffee cherries and contains caffeine, chlorogenic acid, trigonelline, diterpenes and fibre. We investigated the attenuation of signs of metabolic syndrome induced by high-carbohydrate, high-fat diet in rats by dietary supplementation with 5% freeze-dried coffee pulp for the final 8 weeks of a 16-week protocol. Coffee pulp decreased body weight, feed efficiency and abdominal fat; normalised systolic blood pressure, left ventricular diastolic stiffness, and plasma concentrations of triglycerides and non-esterified fatty acids; and improved glucose tolerance in rats fed high-carbohydrate, high-fat diet. Further, the gut microbiota was modulated with high-carbohydrate, high-fat diet and coffee pulp supplementation and 14 physiological parameters were correlated with the changes in bacterial community structures. This study suggested that coffee pulp, as a waste from the coffee industry, is useful as a functional food for improving obesity-associated metabolic, cardiovascular and liver structure and function, and gut microbiota. Full article
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13 pages, 1543 KiB  
Article
A Cranberry Concentrate Decreases Adhesion and Invasion of Escherichia coli (AIEC) LF82 In Vitro
by Derek Zhang, Lynn Verstrepen, Jelle De Medts, Cindy Duysburgh, Pieter Van den Abbeele, Massimo Marzorati and Christina Khoo
Pathogens 2021, 10(9), 1217; https://doi.org/10.3390/pathogens10091217 - 18 Sep 2021
Cited by 2 | Viewed by 2559
Abstract
While many beneficial host–microbiota interactions have been described, imbalanced microbiota in the gut is speculated to contribute to the progression and recurrence of chronic inflammatory diseases such as Crohn’s disease (CD). This in vitro study evaluated the impact of a cranberry concentrate Type [...] Read more.
While many beneficial host–microbiota interactions have been described, imbalanced microbiota in the gut is speculated to contribute to the progression and recurrence of chronic inflammatory diseases such as Crohn’s disease (CD). This in vitro study evaluated the impact of a cranberry concentrate Type M (CTM) on adherent-invasive Escherichia coli (AIEC) LF82, a pathobiont associated with CD. Different stages of pathogenic infection were investigated: (i) colonization of the mucus layer, and (ii) adhesion to and (iii) invasion of the epithelial cells. Following 48 h of fecal batch incubation, 0.5 and 1 mM of CTM significantly altered AIEC LF82 levels in a simulated mucus layer, resulting in a decrease of 50.5% in the untreated blank, down to 43.0% and 11.4%, respectively. At 1 mM of CTM, the significant decrease in the levels of AIEC LF82 coincided with a stimulation of the metabolic activity of the background microbiota. The increased levels of health-associated acetate (+7.9 mM) and propionate levels (+3.5 mM) suggested selective utilization of CTM by host microorganisms. Furthermore, 1 mM of both fermented and unfermented CTM decreased the adhesion and invasion of human-derived epithelial Caco-2 cells by AIEC LF82. Altogether, this exploratory in vitro study demonstrates the prebiotic potential of CTM and supports its antipathogenic effects through direct and/or indirect modulation of the gut microbiome. Full article
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11 pages, 3961 KiB  
Article
Association of Fungi and Archaea of the Gut Microbiota with Crohn’s Disease in Pediatric Patients—Pilot Study
by Agnieszka Krawczyk, Dominika Salamon, Kinga Kowalska-Duplaga, Tomasz Bogiel and Tomasz Gosiewski
Pathogens 2021, 10(9), 1119; https://doi.org/10.3390/pathogens10091119 - 01 Sep 2021
Cited by 11 | Viewed by 2555
Abstract
The composition of bacteria is often altered in Crohn’s disease (CD), but its connection to the disease is not fully understood. Gut archaea and fungi have recently been suggested to play a role as well. In our study, the presence and number of [...] Read more.
The composition of bacteria is often altered in Crohn’s disease (CD), but its connection to the disease is not fully understood. Gut archaea and fungi have recently been suggested to play a role as well. In our study, the presence and number of selected species of fungi and archaea in pediatric patients with CD and healthy controls were evaluated. Stool samples were collected from children with active CD (n = 54), non-active CD (n = 37) and control subjects (n = 33). The prevalence and the number of selected microorganisms were assessed by real-time PCR. The prevalence of Candida tropicalis was significantly increased in active CD compared to non-active CD and the control group (p = 0.011 and p = 0.036, respectively). The number of Malassezia spp. cells was significantly lower in patients with active CD compared to the control group, but in non-active CD, a significant increase was observed (p = 0.005 and p = 0.020, respectively). There were no statistically significant differences in the colonization by archaea. The obtained results indicate possible correlations with the course of the CD; however, further studies of the entire archeobiome and the mycobiome are necessary in order to receive a complete picture. Full article
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17 pages, 3462 KiB  
Article
2′FL and LNnT Exert Antipathogenic Effects against C. difficile ATCC 9689 In Vitro, Coinciding with Increased Levels of Bifidobacteriaceae and/or Secondary Bile Acids
by Louise Kristine Vigsnaes, Jonas Ghyselinck, Pieter Van den Abbeele, Bruce McConnell, Frédéric Moens, Massimo Marzorati and Danica Bajic
Pathogens 2021, 10(8), 927; https://doi.org/10.3390/pathogens10080927 - 22 Jul 2021
Cited by 12 | Viewed by 3101
Abstract
Clostridioides difficile (formerly Clostridium difficile) infection (CDI) is one of the most common hospital-acquired infections, which is often triggered by a dysbiosed indigenous gut microbiota (e.g., upon antibiotic therapy). Symptoms can be as severe as life-threatening colitis. The current study assessed the [...] Read more.
Clostridioides difficile (formerly Clostridium difficile) infection (CDI) is one of the most common hospital-acquired infections, which is often triggered by a dysbiosed indigenous gut microbiota (e.g., upon antibiotic therapy). Symptoms can be as severe as life-threatening colitis. The current study assessed the antipathogenic potential of human milk oligosaccharides (HMOs), i.e., 2′-O-fucosyllactose (2′FL), lacto-N-neotetraose (LNnT), and a combination thereof (MIX), against C. difficile ATCC 9689 using in vitro gut models that allowed the evaluation of both direct and, upon microbiota modulation, indirect effects. During a first 48 h fecal batch study, dysbiosis and CDI were induced by dilution of the fecal inoculum. For each of the three donors tested, C. difficile levels strongly decreased (with >4 log CFU/mL) upon treatment with 2′FL, LNnT and MIX versus untreated blanks, coinciding with increased acetate/Bifidobacteriaceae levels. Interindividual differences among donors at an intermediate time point suggested that the antimicrobial effect was microbiota-mediated rather than being a direct effect of the HMOs. During a subsequent 11 week study with the PathogutTM model (specific application of the Simulator of the Human Intestinal Microbial Ecosystem (SHIME®)), dysbiosis and CDI were induced by clindamycin (CLI) treatment. Vancomycin (VNC) treatment cured CDI, but the further dysbiosis of the indigenous microbiota likely contributed to CDI recurrence. Upon co-supplementation with VNC, both 2′FL and MIX boosted microbial activity (acetate and to lesser extent propionate/butyrate). Moreover, 2′FL avoided CDI recurrence, potentially because of increased secondary bile acid production. Overall, while not elucidating the exact antipathogenic mechanisms-of-action, the current study highlights the potential of HMOs to combat CDI recurrence, help the gut microbial community recover after antibiotic treatment, and hence counteract the adverse effects of antibiotic therapies. Full article
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18 pages, 1284 KiB  
Article
In vitro–in vivo Validation of Stimulatory Effect of Oat Ingredients on Lactobacilli
by Cindy Duysburgh, Pieter Van den Abbeele, Alison Kamil, Lisa Fleige, Peter John De Chavez, YiFang Chu, Wiley Barton, Orla O’Sullivan, Paul D. Cotter, Karina Quilter, Susan A. Joyce, Mike Murphy, Gillian DunnGalvin, Timothy G Dinan and Massimo Marzorati
Pathogens 2021, 10(2), 235; https://doi.org/10.3390/pathogens10020235 - 19 Feb 2021
Cited by 8 | Viewed by 4467
Abstract
The prebiotic activity of a commercially available oat product and a novel oat ingredient, at similar β-glucan loads, was tested using a validated in vitro gut model (M-SHIME®). The novel oat ingredient was tested further at lower β-glucan loads in vitro, [...] Read more.
The prebiotic activity of a commercially available oat product and a novel oat ingredient, at similar β-glucan loads, was tested using a validated in vitro gut model (M-SHIME®). The novel oat ingredient was tested further at lower β-glucan loads in vitro, while the commercially available oat product was assessed in a randomised, single-blind, placebo-controlled, and cross-over human study. Both approaches focused on healthy individuals with mild hypercholesterolemia. In vitro analysis revealed that both oat products strongly stimulated Lactobacillaceae and Bifidobacteriaceae in the intestinal lumen and the simulated mucus layer, and corresponded with enhanced levels of acetate and lactate with cross-feeding interactions leading to an associated increase in propionate and butyrate production. The in vitro prebiotic activity of the novel oat ingredient remained at lower β-glucan levels, indicating the prebiotic potential of the novel oat product. Finally, the stimulation of Lactobacillus spp. was confirmed during the in vivo trial, where lactobacilli abundance significantly increased in the overall population at the end of the intervention period with the commercially available oat product relative to the control product, indicating the power of in vitro gut models in predicting in vivo response of the microbial community to dietary modulation. Full article
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