Gastrointestinal Microbiota Impacts Human Health and Disease

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Gut Microbiota".

Deadline for manuscript submissions: closed (30 April 2019) | Viewed by 190992

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Guest Editor
1. The New Zealand Institute for Plant and Food Research Limited (PFR), Private Bag 11600, Palmerston North 4442, New Zealand
2. Riddet Institute, Massey University, Palmerston North 4442, New Zealand
Interests: human gastrointestinal microbiota; food-microbiota; health and disease
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Special Issue Information

Dear Colleagues,

Enormous abundance and diversity of microorganisms that colonize different regions of the human gastrointestinal tract participate in range of metabolic activities and influence many aspects of health and disease. They play an important role in maintaining immune homeostasis, assist in energy harvest from non-digestible dietary components through fermentation in large intestine and generate many bioactive metabolites, such as short chain fatty acids. Equally, dysbiosis is associated with a number of diseases including inflammatory bowel disease, diabetes mellitus, obesity and metabolic syndrome. Gut microbiome research has been revolutionised over the past decade through development of culture independent, high throughput next generation DNA sequencing technology. We are developing much better understanding of the composition of microbial communities of the healthy human gut, defining dominant members. Application of multiple –omic technologies such metabolomics, proteomics, and transcriptomics has further enhanced our ability to decipher the function of the human gut microbiome including its interaction with human host and impact on health. It is now well known that diet is one of the major influences on both major short- and long term composition of human gut microbiome. Dietary manipulation of gut microbiome therefore offers an attractive approach to achieve a favourable health outcome.

Dr. Pramod Gopal
Guest Editor

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Keywords

  • Gastrointestinal health
  • gut microbiome
  • gut-brain axis
  • probiotics
  • prebiotics
  • IBD
  • IBS
  • gut inflammation
  • gut comfort
  • gut function
  • SCFA
  • oligosaccharides

Published Papers (15 papers)

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Research

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13 pages, 1630 KiB  
Article
Detection of Increased Relative Expression Units of Bacteroides and Prevotella, and Decreased Clostridium leptum in Stool Samples from Brazilian Rheumatoid Arthritis Patients: A Pilot Study
by Guilherme S. P. Rodrigues, Leonardo C. F. Cayres, Fernanda P. Gonçalves, Nauyta N. C. Takaoka, André H. Lengert, Aline Tansini, João L. Brisotti, Carolina B. G. Sasdelli and Gislane L. V. de Oliveira
Microorganisms 2019, 7(10), 413; https://doi.org/10.3390/microorganisms7100413 - 01 Oct 2019
Cited by 31 | Viewed by 3540
Abstract
Interactions between gut microbes and disease modifying antirheumatic drugs (DMARDs) have been proposed. The aim of the present study was to evaluate the presence of some specific bacteria in stool samples from Brazilian RA patients receiving DMARDs and correlate these data with diet, [...] Read more.
Interactions between gut microbes and disease modifying antirheumatic drugs (DMARDs) have been proposed. The aim of the present study was to evaluate the presence of some specific bacteria in stool samples from Brazilian RA patients receiving DMARDs and correlate these data with diet, clinical parameters, and cytokines. Stool samples were used for gut bacteria evalutation by qPCR. Serum samples were used to quantify IL-4 and IL-10 by flow cytometer. Statistics were performed by Pearson chi-square, Mann–Whitney U test, and Spearman’s correlation. The study included 20 RA patients and 30 healthy controls. There were no significant differences (p > 0.05) in dietary habits between RA patients and controls. Concerning gut bacteria, we observed an increase in relative expression units (REU) of Bacteroides and Prevotella species in stool samples from patients, and a decrease in REU of Clostridium leptum when compared with healthy controls. Positive correlation between Prevotella and rheumatoid factor was detected. The IL-4 and IL-10 concentrations were increased in patients when compared with controls. We concluded that gut bacteria are different between RA patients receiving DMARDs and healthy controls. Further studies are necessary to determine the real role of gut microbes and their metabolities in clinical response to different DMARDs in RA patients. Full article
(This article belongs to the Special Issue Gastrointestinal Microbiota Impacts Human Health and Disease)
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12 pages, 1025 KiB  
Article
High-Fat Diet Alters the Intestinal Microbiota in Streptozotocin-Induced Type 2 Diabetic Mice
by Sheng Liu, Panpan Qin and Jing Wang
Microorganisms 2019, 7(6), 176; https://doi.org/10.3390/microorganisms7060176 - 16 Jun 2019
Cited by 41 | Viewed by 5952
Abstract
Intestinal microbiota is closely associated with various metabolic diseases such as type 2 diabetes (T2D), and microbiota is definitely affected by diet. However, more work is required to gain detailed information about gut metagenome and their associated impact with diet in T2D patients. [...] Read more.
Intestinal microbiota is closely associated with various metabolic diseases such as type 2 diabetes (T2D), and microbiota is definitely affected by diet. However, more work is required to gain detailed information about gut metagenome and their associated impact with diet in T2D patients. We used a streptozotocin-high-fat diet (HFD) to induce a T2D mouse model and investigated the effect of standard chow diet and HFD on the composition and function of gut microbiota. We found that a HFD could worsen the diabetes status compared with a standard diet. 16S rRNA gene sequencing revealed that a HFD caused a large disturbance to the microbial structure and was linked to an increased ratio of Firmicutes to Bacteroidetes. A HFD increased the bacteria of the Ruminococcaceae and Erysipelotrichaceae family and decreased the bacteria of S24-7 and Rikenellaceae. Meanwhile, a HFD decreased the abundance of Parabacteroides distasonis and Eubacterium dolichum, both of which have previously been reported to alleviate obesity and metabolic dysfunctions. Moreover, PICRUSt-predicted KEGG pathways related to membrane transport, lipid metabolism, and xenobiotics biodegradation and metabolism were significantly elevated in HFD-fed T2D mice. Our results provide insights into dietary and nutritional approaches for improving host metabolism and ameliorating T2D. Full article
(This article belongs to the Special Issue Gastrointestinal Microbiota Impacts Human Health and Disease)
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13 pages, 3226 KiB  
Article
Engineered Lactococcus lactis Secreting IL-23 Receptor-Targeted REX Protein Blockers for Modulation of IL-23/Th17-Mediated Inflammation
by Tina Vida Plavec, Milan Kuchař, Anja Benko, Veronika Lišková, Jiří Černý, Aleš Berlec and Petr Malý
Microorganisms 2019, 7(5), 152; https://doi.org/10.3390/microorganisms7050152 - 27 May 2019
Cited by 23 | Viewed by 4865
Abstract
Lactococcus lactis, a probiotic bacterium of food origin, has recently been demonstrated as a suitable strain for the production and in vivo delivery of therapeutically important proteins into the gut. We aimed to engineer recombinant L. lactis cells producing/secreting REX binding proteins [...] Read more.
Lactococcus lactis, a probiotic bacterium of food origin, has recently been demonstrated as a suitable strain for the production and in vivo delivery of therapeutically important proteins into the gut. We aimed to engineer recombinant L. lactis cells producing/secreting REX binding proteins that have been described as IL-23 receptor (IL-23R) blockers and IL-23R antagonists suppressing the secretion of cytokine IL-17A, a pivotal step in the T-helper Th17-mediated pro-inflammatory cascade, as well as in the development of autoimmune diseases, including inflammatory bowel disease (IBD). To reach this goal, we introduced cDNA sequences coding for REX009, REX115, and REX125 proteins into plasmid vectors carrying a Usp45 secretion signal, a FLAG tag sequence consensus, and a LysM-containing cA surface anchor (AcmA), thus allowing cell–surface peptidoglycan anchoring. These plasmids, or their non-FLAG/non-AcmA versions, were introduced into L. lactis host cells, thus generating unique recombinant L. lactis–REX strains. We demonstrate that all three REX proteins are expressed in L. lactis cells and are efficiently displayed on the bacterial surface, as tested by flow cytometry using an anti-FLAG antibody conjugate. Upon 10-fold concentration of the conditioned media, a REX125 secretory variant can be detected by Western blotting. To confirm that the FLAG/non-FLAG REX proteins displayed by L. lactis retain their binding specificity, cell-surface interactions of REX proteins with an IL-23R-IgG chimera were demonstrated by flow cytometry. In addition, statistically significant binding of secreted REX009 and REX115 proteins to bacterially produced, soluble human IL-23R was confirmed by ELISA. We conclude that REX-secreting L. lactis strains were engineered that might serve as IL-23/IL-23R blockers in an experimentally induced mouse model of colitis. Full article
(This article belongs to the Special Issue Gastrointestinal Microbiota Impacts Human Health and Disease)
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21 pages, 4541 KiB  
Article
Oral Beta-Lactamase Protects the Canine Gut Microbiome from Oral Amoxicillin-Mediated Damage
by Sheila Connelly, Brian Fanelli, Nur A. Hasan, Rita R. Colwell and Michael Kaleko
Microorganisms 2019, 7(5), 150; https://doi.org/10.3390/microorganisms7050150 - 27 May 2019
Cited by 10 | Viewed by 4501
Abstract
Antibiotics damage the gut microbiome, which can result in overgrowth of pathogenic microorganisms and emergence of antibiotic resistance. Inactivation of antibiotics in the small intestine represents a novel strategy to protect the colonic microbiota. SYN-004 (ribaxamase) is a beta-lactamase formulated for oral delivery [...] Read more.
Antibiotics damage the gut microbiome, which can result in overgrowth of pathogenic microorganisms and emergence of antibiotic resistance. Inactivation of antibiotics in the small intestine represents a novel strategy to protect the colonic microbiota. SYN-004 (ribaxamase) is a beta-lactamase formulated for oral delivery intended to degrade intravenously administered beta-lactam antibiotics in the gastrointestinal (GI) tract. The enteric coating of ribaxamase protects the enzyme from stomach acid and mediates pH-dependent release in the upper small intestine, the site of antibiotic biliary excretion. Clinical benefit was established in animal and human studies in which ribaxamase was shown to degrade ceftriaxone in the GI tract, thereby preserving the gut microbiome, significantly reducing Clostridioides difficile disease, and attenuating antibiotic resistance. To expand ribaxamase utility to oral beta-lactams, delayed release formulations of ribaxamase, SYN-007, were engineered to allow enzyme release in the lower small intestine, distal to the site of oral antibiotic absorption. Based on in vitro dissolution profiles, three SYN-007 formulations were selected for evaluation in a canine model of antibiotic-mediated gut dysbiosis. Dogs received amoxicillin (40 mg/kg, PO, TID) +/- SYN-007 (10 mg, PO, TID) for five days. Serum amoxicillin levels were measured after the first and last antibiotic doses and gut microbiomes were evaluated using whole genome shotgun sequence metagenomics analyses of fecal DNA prior to and after antibiotic treatment. Serum amoxicillin levels did not significantly differ +/- SYN-007 after the first dose for all SYN-007 formulations, while only one SYN-007 formulation did not significantly reduce systemic antibiotic concentrations after the last dose. Gut microbiomes of animals receiving amoxicillin alone displayed significant loss of diversity and emergence of antibiotic resistance genes. In contrast, for animals receiving amoxicillin + SYN-007, microbiome diversities were not altered significantly and the presence of antibiotic resistance genes was reduced. These data demonstrate that SYN-007 diminishes amoxicillin-mediated microbiome disruption and mitigates emergence and propagation of antibiotic resistance genes without interfering with antibiotic systemic absorption. Thus, SYN-007 has the potential to protect the gut microbiome by inactivation of beta-lactam antibiotics when administered by both oral and parenteral routes and to reduce emergence of antibiotic-resistant pathogens. Full article
(This article belongs to the Special Issue Gastrointestinal Microbiota Impacts Human Health and Disease)
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13 pages, 1458 KiB  
Article
Refined versus Extra Virgin Olive Oil High-Fat Diet Impact on Intestinal Microbiota of Mice and Its Relation to Different Physiological Variables
by Nieves Martínez, Isabel Prieto, Marina Hidalgo, Ana Belén Segarra, Ana M. Martínez-Rodríguez, Antonio Cobo, Manuel Ramírez, Antonio Gálvez and Magdalena Martínez-Cañamero
Microorganisms 2019, 7(2), 61; https://doi.org/10.3390/microorganisms7020061 - 23 Feb 2019
Cited by 30 | Viewed by 5200
Abstract
Extra virgin olive oil (EVOO) has been reported to have a distinct influence on gut microbiota in comparison to other fats, with its physiological benefits widely studied. However, a large proportion of the population consumes olive oil after a depurative process that not [...] Read more.
Extra virgin olive oil (EVOO) has been reported to have a distinct influence on gut microbiota in comparison to other fats, with its physiological benefits widely studied. However, a large proportion of the population consumes olive oil after a depurative process that not only mellows its taste, but also deprives it of polyphenols and other minority components. In this study, we compare the influence on the intestinal microbiota of a diet high in this refined olive oil (ROO) with other fat-enriched diets. Swiss Webster mice were fed standard or a high-fat diet enriched with EVOO, ROO, or butter (BT). Physiological parameters were also evaluated. At the end of the feeding period, DNA was extracted from feces and the 16S rRNA was pyrosequenced. The group fed ROO behaved differently to the EVOO group in half the families with statistically significant differences among the diets, with higher comparative levels in three families—Desulfovibrionaceae, Spiroplasmataceae, and Helicobacteraceae—correlating with total cholesterol. These results are again indicative of a link between specific diets, certain physiological parameters and the prevalence of some taxa, but also support the possibility that polyphenols and minor components of EVOO are involved in some of the proposed effects of this fat through the modulation of the intestinal microbiota Full article
(This article belongs to the Special Issue Gastrointestinal Microbiota Impacts Human Health and Disease)
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11 pages, 3537 KiB  
Article
Effects of Bifidobacterium bifidum in Mice Infected with Citrobacter rodentium
by Bijun Wen, Amel Taibi, Christopher R. Villa, Shin-Hann Lee, Sofia Sagaidak and Elena M. Comelli
Microorganisms 2019, 7(2), 51; https://doi.org/10.3390/microorganisms7020051 - 14 Feb 2019
Cited by 5 | Viewed by 4012
Abstract
In vitro and in vivo studies suggest that selected Bifidobacterium bifidum strains sustain intestinal homeostasis. This study aimed to examine whether the administration of B. bifidum MIMBb75 (BB75) attenuates Citrobacter rodentium infection, a murine model for enteric infection and inflammatory bowel disease in [...] Read more.
In vitro and in vivo studies suggest that selected Bifidobacterium bifidum strains sustain intestinal homeostasis. This study aimed to examine whether the administration of B. bifidum MIMBb75 (BB75) attenuates Citrobacter rodentium infection, a murine model for enteric infection and inflammatory bowel disease in humans. C57Bl6/J mice were randomized to receive BB75 daily starting before or after C. rodentium infection. BB75 load and infection kinetics were monitored. On day 10 post-infection (p.i.), histological parameters of the large intestine were assessed. Barrier integrity was evaluated by pathogen translocation to secondary organs and in vivo permeability test. Fecal C. rodentium load peaked at 1010 CFU/g at day 10 p.i., with clearance at day 24 p.i., regardless of probiotic treatment. BB75 administration resulted in 107 cells/g of feces with no effect of timing of administration. BB75 treatment did not attenuate C. rodentium-induced crypt hyperplasia nor inflammation. C. rodentium and BB75 can co-exist in the gut with no mutual displacement. However, BB75 cannot counteract C. rodentium pathology. Our findings provide insight for the understanding of probiotics behavior and their clinical relevance in intestinal inflammation. Full article
(This article belongs to the Special Issue Gastrointestinal Microbiota Impacts Human Health and Disease)
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14 pages, 2308 KiB  
Article
Identification, Characterization, and Formulation of a Novel Carbapenemase Intended to Prevent Antibiotic-Mediated Gut Dysbiosis
by Sheila Connelly, Todd Parsley, Hui Ge and Michael Kaleko
Microorganisms 2019, 7(1), 22; https://doi.org/10.3390/microorganisms7010022 - 16 Jan 2019
Cited by 5 | Viewed by 3940
Abstract
Antibiotics can damage the gut microbiome leading to opportunistic infections and the emergence of antibiotic resistance. Microbiome protection via antibiotic inactivation in the gastrointestinal (GI) tract represents a strategy to limit antibiotic exposure of the colonic microbiota. Proof of concept for this approach [...] Read more.
Antibiotics can damage the gut microbiome leading to opportunistic infections and the emergence of antibiotic resistance. Microbiome protection via antibiotic inactivation in the gastrointestinal (GI) tract represents a strategy to limit antibiotic exposure of the colonic microbiota. Proof of concept for this approach was achieved with an orally-administered beta-lactamase enzyme, SYN-004 (ribaxamase), that was demonstrated to degrade ceftriaxone excreted into the GI tract and protect the gut microbiome from antibiotic-mediated dysbiosis. Ribaxamase efficiently degrades penicillin and cephalosporin beta-lactam antibiotics, but is not active against carbapenems. To expand this microbiome protection strategy to include all classes of beta-lactams, three distinct carbapenemases were evaluated for manufacturability, antibiotic degradation spectrum, and stability in human intestinal fluid. E. coli production strains were generated for P2A, a novel metallo-enzyme isolated from B. cereus, New Delhi metallo-beta-lactamase (NDM), and Klebsiella pneumoniae carbapenemase (KPC). While all three enzymes effectively inactivated a broad range of antibiotics, including penicillins, most cephalosporins, and carbapenems in vitro, only P2A retained biological activity when incubated with human chyme. As functional stability in the intestinal tract is a key requirement for an orally-delivered enzyme, P2A was chosen as a potential clinical candidate. An enteric formulation of P2A was developed, called SYN-006, that was inert under high acid conditions, with enzyme dissolution occurring at pH > 5.5. SYN-006 has the potential to expand microbiome protection via antibiotic inactivation to include all classes of beta-lactam antibiotics. Full article
(This article belongs to the Special Issue Gastrointestinal Microbiota Impacts Human Health and Disease)
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15 pages, 1439 KiB  
Article
A Metabolomic-Based Evaluation of the Role of Commensal Microbiota throughout the Gastrointestinal Tract in Mice
by Yuri Yamamoto, Yumiko Nakanishi, Shinnosuke Murakami, Wanping Aw, Tomoya Tsukimi, Ryoko Nozu, Masami Ueno, Kyoji Hioki, Kenji Nakahigashi, Akiyoshi Hirayama, Masahiro Sugimoto, Tomoyoshi Soga, Mamoru Ito, Masaru Tomita and Shinji Fukuda
Microorganisms 2018, 6(4), 101; https://doi.org/10.3390/microorganisms6040101 - 29 Sep 2018
Cited by 22 | Viewed by 4893
Abstract
Commensal microbiota colonize the surface of our bodies. The inside of the gastrointestinal tract is one such surface that provides a habitat for them. The gastrointestinal tract is a long organ system comprising of various parts, and each part possesses various functions. It [...] Read more.
Commensal microbiota colonize the surface of our bodies. The inside of the gastrointestinal tract is one such surface that provides a habitat for them. The gastrointestinal tract is a long organ system comprising of various parts, and each part possesses various functions. It has been reported that the composition of intestinal luminal metabolites between the small and large intestine are different; however, comprehensive metabolomic and commensal microbiota profiles specific to each part of the gastrointestinal lumen remain obscure. In this study, by using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS)-based metabolome and 16S rRNA gene-based microbiome analyses of specific pathogen-free (SPF) and germ-free (GF) murine gastrointestinal luminal profiles, we observed the different roles of commensal microbiota in each part of the gastrointestinal tract involved in carbohydrate metabolism and nutrient production. We found that the concentrations of most amino acids in the SPF small intestine were higher than those in the GF small intestine. Furthermore, sugar alcohols such as mannitol and sorbitol accumulated only in the GF large intestine, but not in the SPF large intestine. On the other hand, pentoses, such as arabinose and xylose, gradually accumulated from the cecum to the colon only in SPF mice, but were undetected in GF mice. Correlation network analysis between the gastrointestinal microbes and metabolites showed that niacin metabolism might be correlated to Methylobacteriaceae. Collectively, commensal microbiota partially affects the gastrointestinal luminal metabolite composition based on their metabolic dynamics, in cooperation with host digestion and absorption. Full article
(This article belongs to the Special Issue Gastrointestinal Microbiota Impacts Human Health and Disease)
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Review

Jump to: Research

13 pages, 1092 KiB  
Review
The Gut Microbiota in Cardiovascular Disease and Arterial Thrombosis
by Anna Lässiger-Herfurth, Giulia Pontarollo, Alexandra Grill and Christoph Reinhardt
Microorganisms 2019, 7(12), 691; https://doi.org/10.3390/microorganisms7120691 - 13 Dec 2019
Cited by 19 | Viewed by 4641
Abstract
The gut microbiota has emerged as a contributing factor in the development of atherosclerosis and arterial thrombosis. Metabolites from the gut microbiota, such as trimethylamine N-oxide and short chain fatty acids, were identified as messengers that induce cell type-specific signaling mechanisms and immune [...] Read more.
The gut microbiota has emerged as a contributing factor in the development of atherosclerosis and arterial thrombosis. Metabolites from the gut microbiota, such as trimethylamine N-oxide and short chain fatty acids, were identified as messengers that induce cell type-specific signaling mechanisms and immune reactions in the host vasculature, impacting the development of cardiovascular diseases. In addition, microbial-associated molecular patterns drive atherogenesis and the microbiota was recently demonstrated to promote arterial thrombosis through Toll-like receptor signaling. Furthermore, by the use of germ-free mouse models, the presence of a gut microbiota was shown to influence the synthesis of endothelial adhesion molecules. Hence, the gut microbiota is increasingly being recognized as an influencing factor of arterial thrombosis and attempts of dietary pre- or probiotic modulation of the commensal microbiota, to reduce cardiovascular risk, are becoming increasingly significant. Full article
(This article belongs to the Special Issue Gastrointestinal Microbiota Impacts Human Health and Disease)
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18 pages, 1708 KiB  
Review
Glycan Utilisation and Function in the Microbiome of Weaning Infants
by Starin McKeen, Wayne Young, Karl Fraser, Nicole C. Roy and Warren C. McNabb
Microorganisms 2019, 7(7), 190; https://doi.org/10.3390/microorganisms7070190 - 04 Jul 2019
Cited by 13 | Viewed by 4878
Abstract
Glycans are present exogenously in the diet, expressed and secreted endogenously by host cells, and produced by microbes. All of these processes result in them being available to the gut microbiome, firmly placing glycans at the interface of diet–microbe–host interactions. The most dramatic [...] Read more.
Glycans are present exogenously in the diet, expressed and secreted endogenously by host cells, and produced by microbes. All of these processes result in them being available to the gut microbiome, firmly placing glycans at the interface of diet–microbe–host interactions. The most dramatic shift in dietary sources of glycans occurs during the transition from the milk-based neonatal diet to the diverse omnivorous adult diet, and this has profound effects on the composition of the gut microbiome, gene expression by microbes and host cells, mucin composition, and immune development from innate towards adaptive responses. Understanding the glycan-mediated interactions occurring during this transitional window may inform dietary recommendations to support gut and immune development during a vulnerable age. This review aims to summarise the current state of knowledge on dietary glycan mediated changes that may occur in the infant gut microbiome and immune system during weaning. Full article
(This article belongs to the Special Issue Gastrointestinal Microbiota Impacts Human Health and Disease)
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27 pages, 9890 KiB  
Review
Microbial Population Changes and Their Relationship with Human Health and Disease
by Ana Isabel Álvarez-Mercado, Miguel Navarro-Oliveros, Cándido Robles-Sánchez, Julio Plaza-Díaz, María José Sáez-Lara, Sergio Muñoz-Quezada, Luis Fontana and Francisco Abadía-Molina
Microorganisms 2019, 7(3), 68; https://doi.org/10.3390/microorganisms7030068 - 03 Mar 2019
Cited by 55 | Viewed by 10550
Abstract
Specific microbial profiles and changes in intestinal microbiota have been widely demonstrated to be associated with the pathogenesis of a number of extra-intestinal (obesity and metabolic syndrome) and intestinal (inflammatory bowel disease) diseases as well as other metabolic disorders, such as non-alcoholic fatty [...] Read more.
Specific microbial profiles and changes in intestinal microbiota have been widely demonstrated to be associated with the pathogenesis of a number of extra-intestinal (obesity and metabolic syndrome) and intestinal (inflammatory bowel disease) diseases as well as other metabolic disorders, such as non-alcoholic fatty liver disease and type 2 diabetes. Thus, maintaining a healthy gut ecosystem could aid in avoiding the early onset and development of these diseases. Furthermore, it is mandatory to evaluate the alterations in the microbiota associated with pathophysiological conditions and how to counteract them to restore intestinal homeostasis. This review highlights and critically discusses recent literature focused on identifying changes in and developing gut microbiota-targeted interventions (probiotics, prebiotics, diet, and fecal microbiota transplantation, among others) for the above-mentioned pathologies. We also discuss future directions and promising approaches to counteract unhealthy alterations in the gut microbiota. Altogether, we conclude that research in this field is currently in its infancy, which may be due to the large number of factors that can elicit such alterations, the variety of related pathologies, and the heterogeneity of the population involved. Further research on the effects of probiotics, prebiotics, or fecal transplantations on the composition of the human gut microbiome is necessary. Full article
(This article belongs to the Special Issue Gastrointestinal Microbiota Impacts Human Health and Disease)
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11 pages, 426 KiB  
Review
Probiotics and Colon Cancer
by Lorenzo Drago
Microorganisms 2019, 7(3), 66; https://doi.org/10.3390/microorganisms7030066 - 28 Feb 2019
Cited by 95 | Viewed by 13474
Abstract
Literature has recently highlighted the enormous scientific interest on the relationship between the gut microbiota and colon cancer, and how the use of some selected probiotics can have a future impact on the adverse events which occur during this disease. Although there is [...] Read more.
Literature has recently highlighted the enormous scientific interest on the relationship between the gut microbiota and colon cancer, and how the use of some selected probiotics can have a future impact on the adverse events which occur during this disease. Although there is no clear evidence to claim that probiotics are effective in people with cancer, recent reviews have found that probiotics can significantly reduce the incidence of diarrhea and the average frequency of daily bowel movements. However, most of this evidence needs to be more clinically convincing and further discussed. Undoubtedly, some probiotics, when properly dosed and administered, can have a strong rebalance effect on the gut microbiota and as a consequence a possible positive action on immune modulation of the gastrointestinal tract and on inflammation of the intestinal mucosa. Many recent findings indeed support the hypothesis that the daily use of some selected probiotics can be a feasible approach to effectively protect patients against the risk of some severe consequences due to radiation therapy or chemotherapy. This paper aims to review the most recent articles in order to consider a possible adjuvant approach for the use of certain well-balanced probiotics to help prevent colon cancer and the adverse effects caused by related therapies. Full article
(This article belongs to the Special Issue Gastrointestinal Microbiota Impacts Human Health and Disease)
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21 pages, 1047 KiB  
Review
Potential Role for the Gut Microbiota in Modulating Host Circadian Rhythms and Metabolic Health
by Shanthi G. Parkar, Andries Kalsbeek and James F. Cheeseman
Microorganisms 2019, 7(2), 41; https://doi.org/10.3390/microorganisms7020041 - 31 Jan 2019
Cited by 169 | Viewed by 24995
Abstract
This article reviews the current evidence associating gut microbiota with factors that impact host circadian-metabolic axis, such as light/dark cycles, sleep/wake cycles, diet, and eating patterns. We examine how gut bacteria possess their own daily rhythmicity in terms of composition, their localization to [...] Read more.
This article reviews the current evidence associating gut microbiota with factors that impact host circadian-metabolic axis, such as light/dark cycles, sleep/wake cycles, diet, and eating patterns. We examine how gut bacteria possess their own daily rhythmicity in terms of composition, their localization to intestinal niches, and functions. We review evidence that gut bacteria modulate host rhythms via microbial metabolites such as butyrate, polyphenolic derivatives, vitamins, and amines. Lifestyle stressors such as altered sleep and eating patterns that may disturb the host circadian system also influence the gut microbiome. The consequent disruptions to microbiota-mediated functions such as decreased conjugation of bile acids or increased production of hydrogen sulfide and the resultant decreased production of butyrate, in turn affect substrate oxidation and energy regulation in the host. Thus, disturbances in microbiome rhythms may at least partially contribute to an increased risk of obesity and metabolic syndrome associated with insufficient sleep and circadian misalignment. Good sleep and a healthy diet appear to be essential for maintaining gut microbial balance. Manipulating daily rhythms of gut microbial abundance and activity may therefore hold promise for a chrononutrition-based approach to consolidate host circadian rhythms and metabolic homeorhesis. Full article
(This article belongs to the Special Issue Gastrointestinal Microbiota Impacts Human Health and Disease)
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14 pages, 1667 KiB  
Review
Microbial Fermentation of Dietary Protein: An Important Factor in Diet–Microbe–Host Interaction
by Natalie E. Diether and Benjamin P. Willing
Microorganisms 2019, 7(1), 19; https://doi.org/10.3390/microorganisms7010019 - 13 Jan 2019
Cited by 268 | Viewed by 19321
Abstract
Protein fermentation by gut microbiota contributes significantly to the metabolite pool in the large intestine and may contribute to host amino acid balance. However, we have a limited understanding of the role that proteolytic metabolites have, both in the gut and in systemic [...] Read more.
Protein fermentation by gut microbiota contributes significantly to the metabolite pool in the large intestine and may contribute to host amino acid balance. However, we have a limited understanding of the role that proteolytic metabolites have, both in the gut and in systemic circulation. A review of recent studies paired with findings from previous culture-based experiments suggests an important role for microbial protein fermentation in altering the gut microbiota and generating a diverse range of bioactive molecules which exert wide-ranging host effects. These metabolic products have been shown to increase inflammatory response, tissue permeability, and colitis severity in the gut. They are also implicated in the development of metabolic disease, including obesity, diabetes, and non-alcoholic fatty liver disease (NAFLD). Specific products of proteolytic fermentation such as hydrogen sulfide, ammonia, and p-Cresol may also contribute to the development of colorectal cancer. These findings are in conflict with other studies showing that tryptophan metabolites may improve gut barrier function and attenuate severity in a multiple sclerosis model. Further research examining proteolytic fermentation in the gut may be key to our understanding of how microbial and host metabolism interact affecting health. Full article
(This article belongs to the Special Issue Gastrointestinal Microbiota Impacts Human Health and Disease)
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22 pages, 876 KiB  
Review
What is the Healthy Gut Microbiota Composition? A Changing Ecosystem across Age, Environment, Diet, and Diseases
by Emanuele Rinninella, Pauline Raoul, Marco Cintoni, Francesco Franceschi, Giacinto Abele Donato Miggiano, Antonio Gasbarrini and Maria Cristina Mele
Microorganisms 2019, 7(1), 14; https://doi.org/10.3390/microorganisms7010014 - 10 Jan 2019
Cited by 1700 | Viewed by 75084
Abstract
Each individual is provided with a unique gut microbiota profile that plays many specific functions in host nutrient metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Gut microbiota are composed of different bacteria species taxonomically classified [...] Read more.
Each individual is provided with a unique gut microbiota profile that plays many specific functions in host nutrient metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Gut microbiota are composed of different bacteria species taxonomically classified by genus, family, order, and phyla. Each human’s gut microbiota are shaped in early life as their composition depends on infant transitions (birth gestational date, type of delivery, methods of milk feeding, weaning period) and external factors such as antibiotic use. These personal and healthy core native microbiota remain relatively stable in adulthood but differ between individuals due to enterotypes, body mass index (BMI) level, exercise frequency, lifestyle, and cultural and dietary habits. Accordingly, there is not a unique optimal gut microbiota composition since it is different for each individual. However, a healthy host–microorganism balance must be respected in order to optimally perform metabolic and immune functions and prevent disease development. This review will provide an overview of the studies that focus on gut microbiota balances in the same individual and between individuals and highlight the close mutualistic relationship between gut microbiota variations and diseases. Indeed, dysbiosis of gut microbiota is associated not only with intestinal disorders but also with numerous extra-intestinal diseases such as metabolic and neurological disorders. Understanding the cause or consequence of these gut microbiota balances in health and disease and how to maintain or restore a healthy gut microbiota composition should be useful in developing promising therapeutic interventions. Full article
(This article belongs to the Special Issue Gastrointestinal Microbiota Impacts Human Health and Disease)
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