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

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 30048

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Special Issue Editors

Prof. Dr. Ole Haagen Nielsen

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Guest Editor

Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark
Interests: inflammatory bowel disease; inflammation; mucosal immunology; biologics
Special Issues, Collections and Topics in MDPI journals

Dr. John Gubatan

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Guest Editor

Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Redwood City, CA, USA
Interests: inflammatory bowel disease; immunology; gut microbiome; artificial intelligence; precision medicine

Special Issue Information

Dear Colleagues,

Increasing evidence from animal models and human observational studies have revealed a pivotal role for the gut microbiota in maintaining intestinal homeostasis and digestive health. Pertubations in the composition and function of the gut microbiota have been linked to various disorders of the gastrointestinal tract. Novel insights into the role of specific microbes in diverse digestive diseases hold great translational potential for patients with gastrointestinal disorders.

I kindly invite you to contribute to this Special Issue of Microogranisms focused on the current landscape exploring interactions between the gut microbiome and gastrointestinal diseases in the context of disease pathogenesis and emerging microbial-based biomarkers and therapies. New research articles and reviews that address these topics are invited for submission.

Research areas may include (but are not limited to) the following:

Microbial biomarkers for diagnosis, grading disease severity, and response to therapy in patients with gastrointestinal diseases;
Prebiotics, probiotics, and dietary interventions in patients with gastrointestinal diseases;
Fecal microbial transplant in various gastrointestinal diseases;
Emerging pre-clinical in vitro and in vivo studies modeling gut microbiome and gastrointestinal disease interactions.

We look forward to receiving your contributions.

Prof. Dr. Ole Haagen Nielsen
Dr. John Gubatan
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 submissions that pass pre-check are 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. Microorganisms 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 2700 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
disorders
gastrointestinal tract
digestive diseases

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Published Papers (10 papers)

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Editorial

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2 pages, 162 KiB

Open AccessEditorial

Gut Microbiome and Disorders of the Gastrointestinal Tract

by Alexander Hammerhøj, John Mark Gubatan and Ole Haagen Nielsen

Microorganisms 2024, 12(3), 576; https://doi.org/10.3390/microorganisms12030576 - 13 Mar 2024

Cited by 2 | Viewed by 2043

Abstract

The protective intestinal epithelial barrier is constantly exposed to more than 100 trillion commensal microorganisms (bacteria, archaea, viruses, and fungi), i [...] Full article

(This article belongs to the Special Issue Gut Microbiome and Disorders of the Gastrointestinal Tract)

Research

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10 pages, 1058 KiB

Open AccessCommunication

Small Intestinal Bacterial Overgrowth Is Associated with Poor Prognosis in Cirrhosis

by Irina Efremova, Roman Maslennikov, Aliya Alieva, Elena Poluektova and Vladimir Ivashkin

Microorganisms 2023, 11(4), 1017; https://doi.org/10.3390/microorganisms11041017 - 13 Apr 2023

Cited by 7 | Viewed by 2232

Abstract

Background: Small intestinal bacterial overgrowth (SIBO) is associated with numerous manifestations of cirrhosis. To determine whether the presence of SIBO affects the prognosis in cirrhosis was the aim of the study. Methods: This prospective cohort study included 50 patients. All participants underwent a lactulose hydrogen breath test for SIBO. The follow-up period was 4 years. Results: SIBO was detected in 26 (52.0%) patients: in 10 (52.6%) patients with compensated cirrhosis and in 16 (51.6%) ones with decompensated cirrhosis. Twelve (46.2%) patients with SIBO and four (16.7%) patients without SIBO died within 4 years (p = 0.009). Among patients with decompensated cirrhosis, 8 (50.0%) patients with SIBO and 3 (20.0%) patients without SIBO died (p = 0.027). Among patients with compensated cirrhosis, four (40.0%) patients with SIBO and one (11.1%) patient without SIBO died (p = 0.045). Among patients with SIBO, there was no difference in mortality between patients with compensated and decompensated cirrhosis (p = 0.209). It was the same for patients without SIBO (p = 0.215). SIBO affects the prognosis only in the first year of follow-up in decompensated cirrhosis, and only in subsequent years in compensated cirrhosis. Presence of SIBO (p = 0.028; HR = 4.2(1.2–14.9)) and serum albumin level (p = 0.027) were significant independent risk factors for death in cirrhosis. Conclusions: SIBO is associated with poor prognosis in cirrhosis. Full article

(This article belongs to the Special Issue Gut Microbiome and Disorders of the Gastrointestinal Tract)

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18 pages, 6599 KiB

Open AccessArticle

Lactobacillus salivarius WZ1 Inhibits the Inflammatory Injury of Mouse Jejunum Caused by Enterotoxigenic Escherichia coli K88 by Regulating the TLR4/NF-κB/MyD88 Inflammatory Pathway and Gut Microbiota

by Zhen Wei, Ziqi He, Tongyao Wang, Xiaoxuan Wang, Tiancheng Wang and Miao Long

Microorganisms 2023, 11(3), 657; https://doi.org/10.3390/microorganisms11030657 - 3 Mar 2023

Cited by 3 | Viewed by 2255

Abstract

Replacing antibiotics with probiotics has become an important way to safely and effectively prevent and treat some gastrointestinal diseases. This study was conducted to investigate whether Lactobacillus salivarius WZ1 (L.S) could reduce the inflammatory injury to the mouse jejunum induced by Escherichia coli (ETEC) K88. Forty Kunming mice were randomly divided into four groups with 10 mice in each group. From day 1 to day 14, the control group and the E. coli group were administered with normal saline each day, while the L.S group and the L.S + E. coli group were gavaged with Lactobacillus salivarius WZ1 1 × 10⁸ CFU/mL each day. On the 15th day, the E. coli group and the L.S + E. coli group were intragastrically administered ETEC K88 1 × 10⁹ CFU/mL and sacrificed 24 h later. Our results show that pretreatment with Lactobacillus salivarius WZ1 can dramatically protect the jejunum morphological structure from the changes caused by ETEC K88 and relieve the morphological lesions of the jejunum, inhibiting changes in the mRNA expressions of TNF-α, IL-1β and IL-6 and the protein expressions of TLR4, NF-κB and MyD88 in the intestinal tissue of mice caused by ETEC K88. Moreover, pretreatment with Lactobacillus salivarius WZ1 also increased the relative abundance of beneficial genera such as Lactobacillus and Bifidobacterium and decreased the abundance of harmful genera such as Ralstonia and Helicobacter in the gut. These results demonstrate that Lactobacillus salivarius WZ1 can inhibit the inflammatory damage caused by ETEC K88 in mouse jejunum by regulating the TLR4/NF-κB/MyD88 inflammatory pathway and gut microbiota. Full article

(This article belongs to the Special Issue Gut Microbiome and Disorders of the Gastrointestinal Tract)

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22 pages, 8585 KiB

Open AccessArticle

Presence of Polyketide Synthase (PKS) Gene and Counterpart Virulence Determinants in Klebsiella pneumoniae Strains Enhances Colorectal Cancer Progression In-Vitro

by Christina Parvinder Kaur, Thevambiga Iyadorai, Cynthia Sears, April Camilla Roslani, Jamuna Vadivelu and Chandramathi Samudi

Microorganisms 2023, 11(2), 443; https://doi.org/10.3390/microorganisms11020443 - 9 Feb 2023

Cited by 1 | Viewed by 2717

Abstract

Klebsiella pneumoniae (K. pneumoniae) colonizes the human gut and is a causative factor of pyogenic liver abscess (PLA). Retrospective studies conducted on K. pneumoniae PLA patients revealed subsequent CRC development in later years of their life with increasing prevalence of these strains harbouring polyketide synthase (PKS) genes. To our knowledge there are no known studies directly implicating K. pneumoniae with CRC to date. Our aims are to characterize K. pneumoniae isolates from CRC patients and investigate its effects on cell proliferation in vitro. K. pneumoniae isolates were characterized by screening virulence genes including polyketide synthase (PKS), biofilm assay, antibiotic susceptibility, and string test to determine hypervirulent (hvKp) strains. Solubilised antigens of selected K. pneumoniae isolates were co-cultured with primary colon cell lines and CRC cell lines (Stage I-IV) for 48 h. The enhancement of proliferation was measured through MTT and ECIS assay. Twenty-five percent of K. pneumoniae isolates were PKS-positive out of which 50% were hvKp strains. The majority of the isolates were from the more virulent serotype of K1 (30%) and K2 (50%). PKS-positive K. pneumoniae isolates did not possess genes to confer carbapenem resistance but instead were more highly associated with siderophore genes (aerobactin, enterobactin, and yersiniabactin) and allantoin metabolism genes (allS, allS2). Cell proliferation in primary colon, SW1116 (Stage I), and SW480 (Stage II) CRC cell lines were enhanced when co-cultured with PKS-positive K. pneumoniae antigens. ECIS revealed enhanced cell proliferation upon recurrent antigen exposure. This demonstrates the possible role that PKS-positive K. pneumoniae has in exacerbating CRC progression. Full article

(This article belongs to the Special Issue Gut Microbiome and Disorders of the Gastrointestinal Tract)

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20 pages, 4097 KiB

Open AccessArticle

Could the Microbiota Be a Predictive Factor for the Clinical Response to Probiotic Supplementation in IBS-D? A Cohort Study

by Justine Marchix, Lucille Quénéhervé, Philippe Bordron, Philippe Aubert, Tony Durand, Thibauld Oullier, Claude Blondeau, Samira Ait Abdellah, Stanislas Bruley des Varannes, Samuel Chaffron, Emmanuel Coron and Michel Neunlist

Microorganisms 2023, 11(2), 277; https://doi.org/10.3390/microorganisms11020277 - 20 Jan 2023

Cited by 6 | Viewed by 3016

Abstract

Background: Increasing evidence suggests the beneficial effects of probiotics in irritable bowel syndrome (IBS), but little is known about how they can impact the gut microbiota. Our objective was to evaluate the effects of a multistrain probiotic on IBS symptoms, gut permeability and gut microbiota in patients with diarrhoea-predominant IBS (IBS-D). Methods: Adults with IBS-D were enrolled in an open-label trial to receive a multistrain probiotic for 4 weeks. Abdominal pain, stool frequency, quality of life, gut permeability, and the luminal and adherent microbiota from colonic biopsies were evaluated before and after supplementation. Results: Probiotics significantly improved symptoms and quality of life, despite having no impact on permeability in the global population. In the population stratified by the response, the diarrhoea responders displayed reduced colonic permeability after supplementation. The luminal and adherent microbiota were specifically altered depending on the patients’ clinical responses regarding pain and diarrhoea. Interestingly, we identified a microbial signature in IBS-D patients that could predict a response or lack of response to supplementation. Conclusions: The multistrain probiotic improved the symptoms of IBS-D patients and induced distinct effects on the gut microbiota according to the patient’s clinical response and initial microbiota composition. Our study further supports the need to develop individualised probiotic-based approaches regarding IBS. Full article

(This article belongs to the Special Issue Gut Microbiome and Disorders of the Gastrointestinal Tract)

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9 pages, 1323 KiB

Open AccessCommunication

Gluten Degradation by the Gut Microbiota of Ulcerative Colitis Patients

by Emma Olivia Schultz Harringer, Juliana Durack, Yvette Piceno, Vibeke Andersen and Susan V. Lynch

Microorganisms 2023, 11(1), 12; https://doi.org/10.3390/microorganisms11010012 - 21 Dec 2022

Cited by 1 | Viewed by 2722

Abstract

Several studies have reported improved disease symptomatology in ulcerative colitis (UC) patients consuming a gluten free diet. This observation coupled with diversity depletion in the gut microbiota of UC patients led us to hypothesize that UC-associated enteric microbes differentially metabolize dietary gluten to produce immunogenic products that promote inflammation. Gluten concentration in stool was determined using gluten-specific ELISA, and gluten intake was assessed by food frequency questionnaire (FFQ) in UC (n = 12) and healthy controls (HC; n = 13). Gluten-metabolizing bacteria were isolated on minimal media supplemented with 1% gluten from UC and HC and identified by 16S rRNA profiling. Cell-free culture media from gluten metabolizing gut bacterial isolates was assessed for immunogenicity in vitro using HT29 colonocytes. Compared to HC, UC patients did not consume gluten differently (Mann–Whitney; p > 0.10) and exhibited equivalent levels of gluten in their feces (Mann–Whitney; p = 0.163). The profile of gluten-degrading bacteria isolated from UC stool was distinct (Chi-square; p ≤ 0.0001). Compared with Enterococcus isolates, products of gluten degradation by Bacillus strains induced higher IL8 and lower occludin (Mann–Whitney; p = 0.002 and p = 0.059, respectively) gene expression in colonocytes irrespective of whether they originated from UC or healthy gut. Members of HC and UC microbiota exhibit gluten-degrading ability, metabolites of which influence genes involved in inflammation and barrier function in enteric colonocyte cultures. Preliminary findings of this study warrant further investigations into the mechanisms by which gut microbiota contribute to UC pathogenesis through gluten degradation. Full article

(This article belongs to the Special Issue Gut Microbiome and Disorders of the Gastrointestinal Tract)

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22 pages, 2578 KiB

Open AccessArticle

Is There a Universal Endurance Microbiota?

by Hope Olbricht, Kaitlyn Twadell, Brody Sandel, Craig Stephens and Justen B. Whittall

Microorganisms 2022, 10(11), 2213; https://doi.org/10.3390/microorganisms10112213 - 9 Nov 2022

Cited by 2 | Viewed by 2998

Abstract

Billions of microbes sculpt the gut ecosystem, affecting physiology. Since endurance athletes’ performance is often physiology-limited, understanding the composition and interactions within athletes’ gut microbiota could improve performance. Individual studies describe differences in the relative abundance of bacterial taxa in endurance athletes, suggesting the existence of an “endurance microbiota”, yet the taxa identified are mostly non-overlapping. To narrow down the source of this variation, we created a bioinformatics workflow and reanalyzed fecal microbiota from four 16S rRNA gene sequence datasets associated with endurance athletes and controls, examining diversity, relative abundance, correlations, and association networks. There were no significant differences in alpha diversity among all datasets and only one out of four datasets showed a significant overall difference in bacterial community abundance. When bacteria were examined individually, there were no genera with significantly different relative abundance in all four datasets. Two genera were significantly different in two datasets (Veillonella and Romboutsia). No changes in correlated abundances were consistent across datasets. A power analysis using the variance in relative abundance detected in each dataset indicated that much larger sample sizes will be necessary to detect a modest difference in relative abundance especially given the multitude of covariates. Our analysis confirms several challenges when comparing microbiota in general, and indicates that microbes consistently or universally associated with human endurance remain elusive. Full article

(This article belongs to the Special Issue Gut Microbiome and Disorders of the Gastrointestinal Tract)

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25 pages, 6312 KiB

Open AccessArticle

Comprehensive Phenotyping in Inflammatory Bowel Disease: Search for Biomarker Algorithms in the Transkingdom Interactions Context

by Ayelén D. Rosso, Pablo Aguilera, Sofía Quesada, Florencia Mascardi, Sebastian N. Mascuka, María C. Cimolai, Jimena Cerezo, Renata Spiazzi, Carolina Conlon, Claudia Milano, Gregorio M. Iraola, Alberto Penas-Steinhardt and Fiorella S. Belforte

Microorganisms 2022, 10(11), 2190; https://doi.org/10.3390/microorganisms10112190 - 4 Nov 2022

Cited by 2 | Viewed by 2418

Abstract

Inflammatory bowel disease (IBD) is the most common form of intestinal inflammation associated with a dysregulated immune system response to the commensal microbiota in a genetically susceptible host. IBD includes ulcerative colitis (UC) and Crohn’s disease (CD), both of which are remarkably heterogeneous in their clinical presentation and response to treatment. This translates into a notable diagnostic challenge, especially in underdeveloped countries where IBD is on the rise and access to diagnosis or treatment is not always accessible for chronic diseases. The present work characterized, for the first time in our region, epigenetic biomarkers and gut microbial profiles associated with UC and CD patients in the Buenos Aires Metropolitan area and revealed differences between non-IBD controls and IBD patients. General metabolic functions associated with the gut microbiota, as well as core microorganisms within groups, were also analyzed. Additionally, the gut microbiota analysis was integrated with relevant clinical, biochemical and epigenetic markers considered in the follow-up of patients with IBD, with the aim of generating more powerful diagnostic tools to discriminate phenotypes. Overall, our study provides new insights into data analysis algorithms to promote comprehensive phenotyping tools using quantitative and qualitative analysis in a transkingdom interactions network context. Full article

(This article belongs to the Special Issue Gut Microbiome and Disorders of the Gastrointestinal Tract)

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17 pages, 2351 KiB

Open AccessArticle

Gut Microbiota Associated with Clinical Relapse in Patients with Quiescent Ulcerative Colitis

by Hiroaki Kitae, Tomohisa Takagi, Yuji Naito, Ryo Inoue, Yuka Azuma, Takashi Torii, Katsura Mizushima, Toshifumi Doi, Ken Inoue, Osamu Dohi, Naohisa Yoshida, Kazuhiro Kamada, Kazuhiko Uchiyama, Takeshi Ishikawa, Hideyuki Konishi and Yoshito Itoh

Microorganisms 2022, 10(5), 1044; https://doi.org/10.3390/microorganisms10051044 - 18 May 2022

Cited by 3 | Viewed by 2275

Abstract

The microbiota associated with relapse in patients with quiescent ulcerative colitis (qUC) remains unclear. Our objective was to analyze the fecal microbiota of Japanese patients with qUC and identify the relapse-associated microbiota. In this study, 59 patients with qUC and 59 healthy controls (HCs) were enrolled (UMIN 000019486), and their fecal microbiota was compared using 16S rRNA gene amplicon sequencing. We followed their clinical course up to 3.5 years and analyzed the relapse-associated microbiota. Potential functional changes in the fecal microbiota were evaluated using PICRUSt software and the Kyoto Encyclopedia of Genes and Genomes database. There were significant differences in fecal microbiota diversity between HC and qUC subjects, with 13 taxa characterizing each subject. Despite no significant difference in variation of microbiota in a single sample (α diversity) between patients in sustained remission and relapsed patients, the variation in microbial communities between samples (β diversity) was significantly different. Prevotella was more abundant in the sustained remission patients, whereas Faecalibacterium and Bifidobacterium were more abundant in the relapsed patients. We clustered the entire cohort into four clusters, and Kaplan–Meier analysis revealed the subsequent clinical course of each cluster was different. We identified 48 metabolic pathways associated with each cluster using linear discriminant analysis effect size. We confirmed the difference in microbiota between patients with qUC and HCs and identified three genera associated with relapse. We found that the clusters based on these genera had different subsequent clinical courses and activated different metabolic pathways. Full article

(This article belongs to the Special Issue Gut Microbiome and Disorders of the Gastrointestinal Tract)

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Review

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14 pages, 2138 KiB

Open AccessReview

Gut Microbiome in Inflammatory Bowel Disease: Role in Pathogenesis, Dietary Modulation, and Colitis-Associated Colon Cancer

by John Gubatan, Theresa Louise Boye, Michelle Temby, Raoul S. Sojwal, Derek R. Holman, Sidhartha R. Sinha, Stephan R. Rogalla and Ole Haagen Nielsen

Microorganisms 2022, 10(7), 1371; https://doi.org/10.3390/microorganisms10071371 - 7 Jul 2022

Cited by 25 | Viewed by 6230

Abstract

The gut microbiome has increasingly been recognized as a critical and central factor in inflammatory bowel disease (IBD). Here, we review specific microorganisms that have been suggested to play a role in the pathogenesis of IBD and the current state of fecal microbial transplants as a therapeutic strategy in IBD. We discuss specific nutritional and dietary interventions in IBD and their effects on gut microbiota composition. Finally, we examine the role and mechanisms of the gut microbiome in mediating colitis-associated colon cancer. Full article

(This article belongs to the Special Issue Gut Microbiome and Disorders of the Gastrointestinal Tract)

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