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Gut Microbiota and Metabolic Diseases

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 (21 December 2022) | Viewed by 33001

Special Issue Editors


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Guest Editor
Department of Anaesthesia and Intensive Care, Chinese University of Hong Kong, Hong Kong 999077, China
Interests: cell proliferation; autophagy; colon cancer; gastric cancer
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Lee Kong Chian School of Medicine, Nanyang Technological University of Singapore, Singapore 308232, Singapore
Interests: microbiome; nutrition; digestive diseases; metabolic syndrome; obesity
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Metabolic diseases, including obesity, diabetes mellitus, dyslipidemia, and fatty liver disease, represent a global epidemic and markedly heighten the risks for potentially life-threatening complications, including cardiovascular diseases, cancer, and stroke. With the recent advancements in metagenomics, it has now been shown that these metabolic disorders are closely associated with the dysbiotic gut microbiota. Functionally, metabolic disease-associated gut microbes could contribute to disease development via disrupting the intestinal barrier function, releasing microbe-associated molecular patterns (MAMPs) and toxins, modulating bile acid metabolism, and producing immunologically and metabolically bioactive metabolites (e.g., branched chain amino acids, trimethylamine). The gut microbiota is also directly involved in energy harvest and controls satiety and food intake through the gut–brain axis. In this respect, modification of the gut microbiota has been proposed as a novel strategy to prevent or treat metabolic disorders.

This Special Issue is focused on the mechanistic aspect by which the dysbiotic gut microbiota interacts with the host to contribute to the pathogenesis of metabolic disorders. Potential topics also include the use of fecal microbiota transplantation and prebiotics/probiotics/postbiotics as novel therapeutics for ameliorating metabolic functions.

Dr. William K.K. Wu
Dr. Sunny H. Wong
Guest Editors

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Keywords

  • metabolic syndromes
  • obesity
  • diabetes mellitus
  • microbiome
  • dyslipidemia
  • adiposity
  • insulin resistance
  • fatty liver disease

Published Papers (8 papers)

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Research

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10 pages, 1367 KiB  
Communication
Short Photoperiod-Dependent Enrichment of Akkermansia spec. as the Major Change in the Intestinal Microbiome of Djungarian Hamsters (Phodopus sungorus)
by Ann-Kathrin Kissmann, Frank Rosenau, Annika Herwig and Victoria Diedrich
Int. J. Mol. Sci. 2023, 24(7), 6605; https://doi.org/10.3390/ijms24076605 - 1 Apr 2023
Cited by 2 | Viewed by 1307
Abstract
The Djungarian hamster (Phodopus sungorus) is a prominent model organism for seasonal acclimatization, showing drastic whole-body physiological adjustments to an energetically challenging environment, which are considered to also involve the gut microbiome. Fecal samples of hamsters in long photoperiod and again [...] Read more.
The Djungarian hamster (Phodopus sungorus) is a prominent model organism for seasonal acclimatization, showing drastic whole-body physiological adjustments to an energetically challenging environment, which are considered to also involve the gut microbiome. Fecal samples of hamsters in long photoperiod and again after twelve weeks in short photoperiod were analyzed by 16S-rRNA sequencing to evaluate seasonal changes in the respective gut microbiomes. In both photoperiods, the overall composition was stable in the major superordinate phyla of the microbiota, with distinct and delicate changes of abundance in phyla representing each <1% of all. Elusimicrobia, Tenericutes, and Verrucomicrobia were exclusively present in short photoperiod hamsters. In contrast to Elusimicrobium and Aneroplasma as representatives of Elusimicrobia and Tenericutes, Akkermansia muciniphila is a prominent gut microbiome inhabitant well described as important in the health context of animals and humans, including neurodegenerative diseases and obesity. Since diet was not changed, Akkermansia enrichment appears to be a direct consequence of short photoperiod acclimation. Future research will investigate whether the Djungarian hamster intestinal microbiome is responsible for or responsive to seasonal acclimation, focusing on probiotic supplementation. Full article
(This article belongs to the Special Issue Gut Microbiota and Metabolic Diseases)
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17 pages, 2339 KiB  
Article
Moderating Gut Microbiome/Mitochondrial Axis in Oxazolone Induced Ulcerative Colitis: The Evolving Role of β-Glucan and/or, Aldose Reductase Inhibitor, Fidarestat
by Omnia Safwat El-Deeb, Rasha Osama Elesawy, Amira K. Eltokhy, Hanan Alsaeid Al-Shenawy, Heba Bassiony Ghanem, Fatma H. Rizk, Ramez AE Barhoma, Rania H. Shalaby, Amal M. Abdelsattar, Shaimaa S. Mashal, Kareman Ahmed Eshra, Radwa Mahmoud El-Sharaby, Dina Adam Ali and Rowida Raafat Ibrahim
Int. J. Mol. Sci. 2023, 24(3), 2711; https://doi.org/10.3390/ijms24032711 - 31 Jan 2023
Cited by 3 | Viewed by 2268
Abstract
A mechanistic understanding of the dynamic interactions between the mitochondria and the gut microbiome is thought to offer innovative explanations for many diseases and thus provide innovative management approaches, especially in GIT-related autoimmune diseases, such as ulcerative colitis (UC). β-Glucans, important components of [...] Read more.
A mechanistic understanding of the dynamic interactions between the mitochondria and the gut microbiome is thought to offer innovative explanations for many diseases and thus provide innovative management approaches, especially in GIT-related autoimmune diseases, such as ulcerative colitis (UC). β-Glucans, important components of many nutritious diets, including oats and mushrooms, have been shown to exhibit a variety of biological anti-inflammatory and immune-modulating actions. Our research study sought to provide insight into the function of β-glucan and/or fidarestat in modifying the microbiome/mitochondrial gut axis in the treatment of UC. A total of 50 Wistar albino male rats were grouped into five groups: control, UC, β-Glucan, Fidarestat, and combined treatment groups. All the groups were tested for the presence of free fatty acid receptors 2 and 3 (FFAR-2 and -3) and mitochondrial transcription factor A (TFAM) mRNA gene expressions. The reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and ATP content were found. The trimethylamine N-oxide (TMAO) and short-chain fatty acid (SCFA) levels were also examined. Nuclear factor kappa β (NF-kβ), nuclear factor (erythroid-2)-related factor 2 (Nrf2) DNA binding activity, and peroxisome proliferator-activated receptor gamma co-activator-1 (PGC-1) were identified using the ELISA method. We observed a substantial increase FFAR-2, -3, and TFAM mRNA expression after the therapy. Similar increases were seen in the ATP levels, MMP, SCFA, PGC-1, and Nrf2 DNA binding activity. The levels of ROS, TMAO, and NF-kβ, on the other hand, significantly decreased. Using β-glucan and fidarestat together had unique therapeutic benefits in treating UC by focusing on the microbiota/mitochondrial axis, opening up a new avenue for a potential treatment for such a complex, multidimensional illness. Full article
(This article belongs to the Special Issue Gut Microbiota and Metabolic Diseases)
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15 pages, 2579 KiB  
Article
Unhealthy Diets Induce Distinct and Regional Effects on Intestinal Inflammatory Signalling Pathways and Long-Lasting Metabolic Dysfunction in Rats
by Sofia Nogueira, Joana Barbosa, Juliana Faria, Susana I. Sá, Armando Cardoso, Raquel Soares, Bruno M. Fonseca and Sandra Leal
Int. J. Mol. Sci. 2022, 23(18), 10984; https://doi.org/10.3390/ijms231810984 - 19 Sep 2022
Viewed by 3741
Abstract
The intestinal epithelium is a principal site for environmental agents’ detection. Several inflammation- and stress-related signalling pathways have been identified as key players in these processes. However, it is still unclear how the chronic intake of inadequate nutrients triggers inflammatory signalling pathways in [...] Read more.
The intestinal epithelium is a principal site for environmental agents’ detection. Several inflammation- and stress-related signalling pathways have been identified as key players in these processes. However, it is still unclear how the chronic intake of inadequate nutrients triggers inflammatory signalling pathways in different intestinal regions. We aimed to evaluate the impact of unhealthy dietary patterns, starting at a younger age, and the association with metabolic dysfunction, intestinal inflammatory response, and obesity in adulthood. A rat model was used to evaluate the effects of the consumption of sugary beverages (HSD) and a Western diet (WD), composed of ultra-processed foods. Both diets showed a positive correlation with adiposity index, but a positive correlation was found between the HSD diet and the levels of blood glucose and triglycerides, whereas the WD diet correlated positively with triglyceride levels. Moreover, a distinct inflammatory response was associated with either the WD or HSD diets. The WD induced an increase in TLR2, TLR4, and nuclear factor-kappa B (NF-κB) intestinal gene expression, with higher levels in the colon and overexpression of the inducible nitric oxide synthase. In turn, the HSD diet induced activation of the TLR2-mediated NF-κB signalling pathway in the small intestine. Altogether, these findings support the concept that early intake of unhealthy foods and nutrients are a main exogenous signal for disturbances of intestinal immune mechanisms and in a region-specific manner, ultimately leading to obesity-related disorders in later life. Full article
(This article belongs to the Special Issue Gut Microbiota and Metabolic Diseases)
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16 pages, 4333 KiB  
Article
Synbiotic Supplementation Modulates Gut Microbiota, Regulates β-Catenin Expression and Prevents Weight Gain in ob/ob Mice: Preliminary Findings
by Sebastião Mauro B. Duarte, José Tadeu Stefano, Lucas A. M. Franco, Roberta C. Martins, Bruna D. G. C. Moraes, Denise Frediani Barbeiro, Nathalia Oliveira, Junia Marielle Teixeira Rodrigues Neri, Bruno Cogliati, Denise Siqueira Vanni, Ester C. Sabino, Flair J. Carrilho and Claudia P. Oliveira
Int. J. Mol. Sci. 2022, 23(18), 10483; https://doi.org/10.3390/ijms231810483 - 10 Sep 2022
Cited by 2 | Viewed by 1675
Abstract
Background: Obesity is one of the main health problems in the world today, and dysbiosis seems to be one of the factors involved. The aim of this study was to examine the impact of synbiotic supplementation on obesity and the microbiota in ob/ob [...] Read more.
Background: Obesity is one of the main health problems in the world today, and dysbiosis seems to be one of the factors involved. The aim of this study was to examine the impact of synbiotic supplementation on obesity and the microbiota in ob/ob mice. Twenty animals were divided into four groups: obese treated (OT), obese control (OC), lean treated (LT) and lean control (LC). All animals received a standard diet for 8 weeks. The treated groups received a synbiotic (Simbioflora-Invictus Farmanutrição Ltd., Sao Paulo, Brazil) in water, while the nontreated groups received only water. After 8 weeks, all animals were sacrificed, and gut tissue and stool samples were collected for mRNA isolation and microbiota analysis, respectively. β-Catenin, occludin, cadherin and zonulin in the gut tissue were analyzed via RT-qPCR. Microbiome DNA was extracted from stool samples and sequenced using an Ion PGM Torrent platform. Results: Synbiotic supplementation reduced body weight gain in the OT group compared with the OC group (p = 0.0398) and was associated with an increase in Enterobacteriaceae (p = 0.005) and a decrease in Cyanobacteria (p = 0.047), Clostridiaceae (p = 0.026), Turicibacterales (p = 0.005) and Coprococcus (p = 0.047). On the other hand, a significant reduction in Sutterella (p = 0.009) and Turicibacter (p = 0.005) bacteria was observed in the LT group compared to the LC group. Alpha and beta diversities were different among all treated groups. β-Catenin gene expression was significantly decreased in the gut tissue of the OT group (p ≤ 0.0001) compared to the other groups. No changes were observed in occludin, cadherin or zonulin gene expression in the gut tissue. Conclusions: Synbiotic supplementation prevents excessive weight gain, modulates the gut microbiota, and reduces β-catenin expression in ob/ob mice. Full article
(This article belongs to the Special Issue Gut Microbiota and Metabolic Diseases)
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12 pages, 6085 KiB  
Article
Enalapril Diminishes the Diabetes-Induced Changes in Intestinal Morphology, Intestinal RAS and Blood SCFA Concentration in Rats
by Kinga Jaworska, Wojciech Kopacz, Mateusz Koper, Mateusz Szudzik, Marta Gawryś-Kopczyńska, Marek Konop, Tomasz Hutsch, Dawid Chabowski and Marcin Ufnal
Int. J. Mol. Sci. 2022, 23(11), 6060; https://doi.org/10.3390/ijms23116060 - 27 May 2022
Cited by 2 | Viewed by 2013
Abstract
Evidence suggests that microbiota-derived metabolites, including short-chain fatty acids (SCFAs) and trimethylamine-oxide (TMAO), affect the course of diabetic multiorgan pathology. We hypothesized that diabetes activates the intestinal renin–angiotensin system (RAS), contributing to gut pathology. Twelve-week-old male rats were divided into three groups: controls, [...] Read more.
Evidence suggests that microbiota-derived metabolites, including short-chain fatty acids (SCFAs) and trimethylamine-oxide (TMAO), affect the course of diabetic multiorgan pathology. We hypothesized that diabetes activates the intestinal renin–angiotensin system (RAS), contributing to gut pathology. Twelve-week-old male rats were divided into three groups: controls, diabetic (streptozotocin-induced) and diabetic treated with enalapril. Histological examination and RT-qPCR were performed to evaluate morphology and RAS expression in the jejunum and the colon. SCFA and TMAO concentrations in stools, portal and systemic blood were evaluated. In comparison to the controls, the diabetic rats showed hyperplastic changes in jejunal and colonic mucosa, increased plasma SCFA, and slightly increased plasma TMAO. The size of the changes was smaller in enalapril-treated rats. Diabetic rats had a lower expression of Mas receptor (MasR) and angiotensinogen in the jejunum whereas, in the colon, the expression of MasR and renin was greater in diabetic rats. Enalapril-treated rats had a lower expression of MasR in the colon. The expression of AT1a, AT1b, and AT2 receptors was similar between groups. In conclusion, diabetes produces morphological changes in the intestines, increases plasma SCFA, and alters the expression of renin and MasR. These alterations were reduced in enalapril-treated rats. Future studies need to evaluate the clinical significance of intestinal pathology in diabetes. Full article
(This article belongs to the Special Issue Gut Microbiota and Metabolic Diseases)
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Review

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27 pages, 1444 KiB  
Review
Gut Dysbiosis and Fecal Microbiota Transplantation in Autoimmune Diseases
by Paulina Belvoncikova, Martin Maronek and Roman Gardlik
Int. J. Mol. Sci. 2022, 23(18), 10729; https://doi.org/10.3390/ijms231810729 - 14 Sep 2022
Cited by 19 | Viewed by 5309
Abstract
Gut microbiota dysbiosis has recently been reported in a number of clinical states, including neurological, psychiatric, cardiovascular, metabolic and autoimmune disorders. Yet, it is not completely understood how colonizing microorganisms are implicated in their pathophysiology and molecular pathways. There are a number of [...] Read more.
Gut microbiota dysbiosis has recently been reported in a number of clinical states, including neurological, psychiatric, cardiovascular, metabolic and autoimmune disorders. Yet, it is not completely understood how colonizing microorganisms are implicated in their pathophysiology and molecular pathways. There are a number of suggested mechanisms of how gut microbiota dysbiosis triggers or sustains extraintestinal diseases; however, none of these have been widely accepted as part of the disease pathogenesis. Recent studies have proposed that gut microbiota and its metabolites could play a pivotal role in the modulation of immune system responses and the development of autoimmunity in diseases such as rheumatoid arthritis, multiple sclerosis or type 1 diabetes. Fecal microbiota transplantation (FMT) is a valuable tool for uncovering the role of gut microbiota in the pathological processes. This review aims to summarize the current knowledge about gut microbiota dysbiosis and the potential of FMT in studying the pathogeneses and therapies of autoimmune diseases. Herein, we discuss the extraintestinal autoimmune pathologies with at least one published or ongoing FMT study in human or animal models. Full article
(This article belongs to the Special Issue Gut Microbiota and Metabolic Diseases)
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23 pages, 9245 KiB  
Review
Interactive Relationships between Intestinal Flora and Bile Acids
by Xiaohua Guo, Edozie Samuel Okpara, Wanting Hu, Chuyun Yan, Yu Wang, Qionglin Liang, John Y. L. Chiang and Shuxin Han
Int. J. Mol. Sci. 2022, 23(15), 8343; https://doi.org/10.3390/ijms23158343 - 28 Jul 2022
Cited by 36 | Viewed by 7150
Abstract
The digestive tract is replete with complex and diverse microbial communities that are important for the regulation of multiple pathophysiological processes in humans and animals, particularly those involved in the maintenance of intestinal homeostasis, immunity, inflammation, and tumorigenesis. The diversity of bile acids [...] Read more.
The digestive tract is replete with complex and diverse microbial communities that are important for the regulation of multiple pathophysiological processes in humans and animals, particularly those involved in the maintenance of intestinal homeostasis, immunity, inflammation, and tumorigenesis. The diversity of bile acids is a result of the joint efforts of host and intestinal microflora. There is a bidirectional relationship between the microbial community of the intestinal tract and bile acids in that, while the microbial flora tightly modulates the metabolism and synthesis of bile acids, the bile acid pool and composition affect the diversity and the homeostasis of the intestinal flora. Homeostatic imbalances of bile acid and intestinal flora systems may lead to the development of a variety of diseases, such as inflammatory bowel disease (IBD), colorectal cancer (CRC), hepatocellular carcinoma (HCC), type 2 diabetes (T2DM), and polycystic ovary syndrome (PCOS). The interactions between bile acids and intestinal flora may be (in)directly involved in the pathogenesis of these diseases. Full article
(This article belongs to the Special Issue Gut Microbiota and Metabolic Diseases)
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15 pages, 788 KiB  
Review
Metagenomic Sequencing for Microbial DNA in Human Samples: Emerging Technological Advances
by Yu Shi, Guoping Wang, Harry Cheuk-Hay Lau and Jun Yu
Int. J. Mol. Sci. 2022, 23(4), 2181; https://doi.org/10.3390/ijms23042181 - 16 Feb 2022
Cited by 31 | Viewed by 8262
Abstract
Whole genome metagenomic sequencing is a powerful platform enabling the simultaneous identification of all genes from entirely different kingdoms of organisms in a complex sample. This technology has revolutionised multiple areas from microbiome research to clinical diagnoses. However, one of the major challenges [...] Read more.
Whole genome metagenomic sequencing is a powerful platform enabling the simultaneous identification of all genes from entirely different kingdoms of organisms in a complex sample. This technology has revolutionised multiple areas from microbiome research to clinical diagnoses. However, one of the major challenges of a metagenomic study is the overwhelming non-microbial DNA present in most of the host-derived specimens, which can inundate the microbial signals and reduce the sensitivity of microorganism detection. Various host DNA depletion methods to facilitate metagenomic sequencing have been developed and have received considerable attention in this context. In this review, we present an overview of current host DNA depletion approaches along with explanations of their underlying principles, advantages and disadvantages. We also discuss their applications in laboratory microbiome research and clinical diagnoses and, finally, we envisage the direction of the further perfection of metagenomic sequencing in samples with overabundant host DNA. Full article
(This article belongs to the Special Issue Gut Microbiota and Metabolic Diseases)
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