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Gut Microbes and Their Metabolites in Health and Disease

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

Deadline for manuscript submissions: closed (30 April 2023) | Viewed by 11518

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Special Issue Editor

Dr. Xiang Zhang

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Guest Editor

1. Department of Medicine and Therapeutics, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong 999077, China
2. State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong 999077, China
Interests: gastrointestinal disease; non-alcoholic steatohepatitis (NASH); gut microbiome; high fat diet

Special Issue Information

Dear Colleagues,

The human microbiome comprises over 100 trillion microbes including bacteria, fungi, and viruses. With advances in both bioinformatic analyses and functional investigations, substantial progress has been achieved in understanding host–microbiome interactions. The gut microbiome has shown its impacts across a variety of physiological functions, while dysbiosis or alterations in the gut microbiome are correlated with the pathogenesis and progression of numerous diseases. The effects of gut-resident bacteria are not limited to the gastrointestinal tract but have far-reaching effects on distal organs through bacteria translocation as well as microbial metabolites.

This Special Issue aims to report the most recent advances in uncovering the gut microbiota and their metabolites in health and diseases. For this Special Issue, we welcome the submission of reviews and original research articles that focus on, but are not limited to, the following themes:

The contribution of a healthy gut microbiome to digestion and immunity of the host;
The impact of a dysbiotic microbiome on the development of gastrointestinal diseases through host–microbiome interaction;
The effect of gut microbiota and metabolites on organs beyond the intestinal lumen including the liver, pancreas, heart, and brain;
Gut microbiota and cancer immunotherapy.

Importantly, articles must include studies of molecular mechanisms; papers only containing clinical trials/data will not be accepted

Dr. Xiang Zhang
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 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. 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 microbiota
metabolites
gastrointestinal diseases
cancer immunotherapy
digestion and immunity of the host

Published Papers (6 papers)

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Research

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21 pages, 9229 KiB

Open AccessArticle

SIRT2 Deficiency Aggravates Diet-Induced Nonalcoholic Fatty Liver Disease through Modulating Gut Microbiota and Metabolites

by Xingyu Li, Yimeng Du, Chunyuan Xue, Xiaofeng Kang, Chao Sun, Huanyan Peng, Liaoxin Fang, Yuchen Han, Xiaojie Xu and Caiyan Zhao

Int. J. Mol. Sci. 2023, 24(10), 8970; https://doi.org/10.3390/ijms24108970 - 18 May 2023

Cited by 5 | Viewed by 1722

Abstract

Non-alcoholic fatty liver disease (NAFLD), characterized by excessive lipid accumulation in hepatocytes, is an increasing global healthcare burden. Sirtuin 2 (SIRT2) functions as a preventive molecule for NAFLD with incompletely clarified regulatory mechanisms. Metabolic changes and gut microbiota imbalance are critical to the pathogenesis of NAFLD. However, their association with SIRT2 in NAFLD progression is still unknown. Here, we report that SIRT2 knockout (KO) mice are susceptible to HFCS (high-fat/high-cholesterol/high-sucrose)-induced obesity and hepatic steatosis accompanied with an aggravated metabolic profile, which indicates SIRT2 deficiency promotes NAFLD-NASH (nonalcoholic steatohepatitis) progression. Under palmitic acid (PA), cholesterol (CHO), and high glucose (Glu) conditions, SIRT2 deficiency promotes lipid deposition and inflammation in cultured cells. Mechanically, SIRT2 deficiency induces serum metabolites alteration including upregulation of L-proline and downregulation of phosphatidylcholines (PC), lysophosphatidylcholine (LPC), and epinephrine. Furthermore, SIRT2 deficiency promotes gut microbiota dysbiosis. The microbiota composition clustered distinctly in SIRT2 KO mice with decreased Bacteroides and Eubacterium, and increased Acetatifactor. In clinical patients, SIRT2 is downregulated in the NALFD patients compared with healthy controls, and is associated with exacerbated progression of normal liver status to NAFLD to NASH in clinical patients. In conclusion, SIRT2 deficiency accelerates HFCS-induced NAFLD-NASH progression by inducing alteration of gut microbiota and changes of metabolites. Full article

(This article belongs to the Special Issue Gut Microbes and Their Metabolites in Health and Disease)

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24 pages, 3011 KiB

Open AccessArticle

Live Cells Imaging and Comparative Phosphoproteomics Uncover Proteins from the Mechanobiome in Entamoeba histolytica

by Gagan Deep Jhingan, Maria Manich, Jean-Christophe Olivo-Marin and Nancy Guillen

Int. J. Mol. Sci. 2023, 24(10), 8726; https://doi.org/10.3390/ijms24108726 - 13 May 2023

Cited by 1 | Viewed by 1371

Abstract

Entamoeba histolytica is a protozoan parasite and the causative agent of amoebiasis in humans. This amoeba invades human tissues by taking advantage of its actin-rich cytoskeleton to move, enter the tissue matrix, kill and phagocyte the human cells. During tissue invasion, E. histolytica moves from the intestinal lumen across the mucus layer and enters the epithelial parenchyma. Faced with the chemical and physical constraints of these diverse environments, E. histolytica has developed sophisticated systems to integrate internal and external signals and to coordinate cell shape changes and motility. Cell signalling circuits are driven by interactions between the parasite and extracellular matrix, combined with rapid responses from the mechanobiome in which protein phosphorylation plays an important role. To understand the role of phosphorylation events and related signalling mechanisms, we targeted phosphatidylinositol 3-kinases followed by live cell imaging and phosphoproteomics. The results highlight 1150 proteins, out of the 7966 proteins within the amoebic proteome, as members of the phosphoproteome, including signalling and structural molecules involved in cytoskeletal activities. Inhibition of phosphatidylinositol 3-kinases alters phosphorylation in important members of these categories; a finding that correlates with changes in amoeba motility and morphology, as well as a decrease in actin-rich adhesive structures. Full article

(This article belongs to the Special Issue Gut Microbes and Their Metabolites in Health and Disease)

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15 pages, 3379 KiB

Open AccessArticle

Lacticaseibacillus rhamnosus ATCC 53103 and Limosilactobacillus reuteri ATCC 53608 Synergistically Boost Butyrate Levels upon Tributyrin Administration Ex Vivo

by Pieter Van den Abbeele, Mallory Goggans, Stef Deyaert, Aurélien Baudot, Michiel Van de Vliet, Marta Calatayud Arroyo and Michael Lelah

Int. J. Mol. Sci. 2023, 24(6), 5859; https://doi.org/10.3390/ijms24065859 - 20 Mar 2023

Cited by 4 | Viewed by 2056

Abstract

Modulation of the gut microbiota is a trending strategy to improve health. While butyrate has been identified as a key health-related microbial metabolite, managing its supply to the host remains challenging. Therefore, this study investigated the potential to manage butyrate supply via tributyrin oil supplementation (TB; glycerol with three butyrate molecules) using the ex vivo SIFR^® (Systemic Intestinal Fermentation Research) technology, a highly reproducible, in vivo predictive gut model that accurately preserves in vivo-derived microbiota and enables addressing interpersonal differences. Dosing 1 g TB/L significantly increased butyrate with 4.1 (±0.3) mM, corresponding with 83 ± 6% of the theoretical butyrate content of TB. Interestingly, co-administration of Limosilactobacillus reuteri ATCC 53608 (REU) and Lacticaseibacillus rhamnosus ATCC 53103 (LGG) markedly enhanced butyrate to levels that exceeded the theoretical butyrate content of TB (138 ± 11% for REU; 126 ± 8% for LGG). Both TB + REU and TB + LGG stimulated Coprococcus catus, a lactate-utilizing, butyrate-producing species. The stimulation of C. catus with TB + REU was remarkably consistent across the six human adults tested. It is hypothesized that LGG and REU ferment the glycerol backbone of TB to produce lactate, a precursor of butyrate. TB + REU also significantly stimulated the butyrate-producing Eubacterium rectale and Gemmiger formicilis and promoted microbial diversity. The more potent effects of REU could be due to its ability to convert glycerol to reuterin, an antimicrobial compound. Overall, both the direct butyrate release from TB and the additional butyrate production via REU/LGG-mediated cross-feeding were highly consistent. This contrasts with the large interpersonal differences in butyrate production that are often observed upon prebiotic treatment. Combining TB with LGG and especially REU is thus a promising strategy to consistently supply butyrate to the host, potentially resulting in more predictable health benefits. Full article

(This article belongs to the Special Issue Gut Microbes and Their Metabolites in Health and Disease)

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Graphical abstract

17 pages, 1932 KiB

Open AccessArticle

Metabolic Potential of the Gut Microbiome Is Significantly Impacted by Conditioning Regimen in Allogeneic Hematopoietic Stem Cell Transplantation Recipients

by Mette Jørgensen, Jens C. Nørgaard, Emma E. Ilett, Ramtin Z. Marandi, Marc Noguera-Julian, Roger Paredes, Daniel D. Murray, Jens Lundgren, Cameron Ross MacPherson and Henrik Sengeløv

Int. J. Mol. Sci. 2022, 23(19), 11115; https://doi.org/10.3390/ijms231911115 - 21 Sep 2022

Cited by 4 | Viewed by 1448

Abstract

Allogeneic hematopoietic stem cell transplantation (aHSCT) is a putative curative treatment for malignant hematologic disorders. During transplantation, the immune system is suppressed/eradicated through a conditioning regimen (non-myeloablative or myeloablative) and replaced with a donor immune system. In our previous study, we showed changes in gut taxonomic profiles and a decrease in bacterial diversity post-transplant. In this study, we expand the cohort with 114 patients and focus on the impact of the conditioning regimens on taxonomic features and the metabolic functions of the gut bacteria. This is, to our knowledge, the first study to examine the metabolic potential of the gut microbiome in this patient group. Adult aHSCT recipients with shotgun sequenced stool samples collected day −30 to +28 relative to aHSCT were included. One sample was selected per patient per period: pre-aHSCT (day −30–0) and post-aHSCT (day 1–28). In total, 254 patients and 365 samples were included. Species richness, alpha diversity, gene richness and metabolic richness were all lower post-aHSCT than pre-aHSCT and the decline was more pronounced for the myeloablative group. The myeloablative group showed a decline in 36 genera and an increase in 15 genera. For the non-myeloablative group, 30 genera decreased and 16 increased with lower fold changes than observed in the myeloablative group. For the myeloablative group, 32 bacterial metabolic functions decreased, and one function increased. For the non-myeloablative group, three functions decreased, and two functions increased. Hence, the changes in taxonomy post-aHSCT caused a profound decline in bacterial metabolic functions especially in the myeloablative group, thus providing new evidence for associations of myeloablative conditioning and gut dysbiosis from a functional perspective. Full article

(This article belongs to the Special Issue Gut Microbes and Their Metabolites in Health and Disease)

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Review

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22 pages, 1240 KiB

Open AccessReview

Molecular Mechanism and Clinical Effects of Probiotics in the Management of Cow’s Milk Protein Allergy

by Ludovica Cela, Giulia Brindisi, Alessandro Gravina, Francesca Pastore, Antonio Semeraro, Ivana Bringheli, Lavinia Marchetti, Rebecca Morelli, Bianca Cinicola, Martina Capponi, Alessandra Gori, Elia Pignataro, Maria Grazia Piccioni, Anna Maria Zicari and Caterina Anania

Int. J. Mol. Sci. 2023, 24(12), 9781; https://doi.org/10.3390/ijms24129781 - 6 Jun 2023

Cited by 4 | Viewed by 2406

Abstract

Cow’s milk protein allergy (CMPA) is the most common food allergy (FA) in infancy, affecting approximately 2% of children under 4 years of age. According to recent studies, the increasing prevalence of FAs can be associated with changes in composition and function of gut microbiota or “dysbiosis”. Gut microbiota regulation, mediated by probiotics, may modulate the systemic inflammatory and immune responses, influencing the development of allergies, with possible clinical benefits. This narrative review collects the actual evidence of probiotics’ efficacy in the management of pediatric CMPA, with a specific focus on the molecular mechanisms of action. Most studies included in this review have shown a beneficial effect of probiotics in CMPA patients, especially in terms of achieving tolerance and improving symptoms. Full article

(This article belongs to the Special Issue Gut Microbes and Their Metabolites in Health and Disease)

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16 pages, 944 KiB

Open AccessReview

Microbial Influences on Immune Checkpoint Inhibitor Response in Melanoma: The Interplay between Skin and Gut Microbiota

by Youssef Bouferraa, Callie Fares, Maroun Bou Zerdan and Lucy Boyce Kennedy

Int. J. Mol. Sci. 2023, 24(11), 9702; https://doi.org/10.3390/ijms24119702 - 2 Jun 2023

Cited by 2 | Viewed by 1910

Abstract

Immunotherapy has revolutionized the treatment of melanoma, but its limitations due to resistance and variable patient responses have become apparent. The microbiota, which refers to the complex ecosystem of microorganisms that inhabit the human body, has emerged as a promising area of research for its potential role in melanoma development and treatment response. Recent studies have highlighted the role of microbiota in influencing the immune system and its response to melanoma, as well as its influence on the development of immune-related adverse events associated with immunotherapy. In this article, we discuss the complex multifactorial mechanisms through which skin and gut microbiota can affect the development of melanoma including microbial metabolites, intra-tumor microbes, UV light, and the immune system. In addition, we will discuss the pre-clinical and clinical studies that have demonstrated the influence of different microbial profiles on response to immunotherapy. Additionally, we will explore the role of microbiota in the development of immune-mediated adverse events. Full article

(This article belongs to the Special Issue Gut Microbes and Their Metabolites in Health and Disease)

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