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Microbiome and Metabolome in the Gastrointestinal Tract

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

Deadline for manuscript submissions: closed (31 July 2023) | Viewed by 28254

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Dr. Ioannis Alexandros Charitos

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Anaesthesia and Intensive Care Assistant Medical Director (EMS-PA) Researcher, Pneumology and Respiratory Rehabilitation Unit, Clinical Scientific Institutes Maugeri (ICS), Research Hospitals of National Interest (IRCCS), Section of Bari, Pavia, Italy
Interests: toxicology; xenobiotics; anesthesia and critical care; human microbiota
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Dear Colleagues,

Certain changes that occur in the human microbiome lead not only to unfavorable conditions for the homeostasis of the organism, but can also facilitate the growth of benign or malignant conditions. This change can be induced and influenced by the microenvironment of each individual microbiota and therefore by internal or external factors such as diet, toxic substances, etc. Both quantitative and qualitative variations of the microbiome (dysbiosis) play important roles in the development of systemic (such as autoimmune diseases) or local diseases (such as intestinal inflammations). Therefore, studying the interactions that the human microbiota of the host has with these factors in more depth plays a crucial role in the prevention and management of certain pathologies. Germ cells interacting with cells and/or their surrounding tissues is important for the maturation of the environment for the development of structural modifications. The eubiotic microbiota regulates the immunity response but also influences the mechanism of action and toxicity of drugs. Considering this, it is important to look for interactions even between the various axes of the microbiota such as gut/brain, gut/liver and others. So far, the biomechanisms underlying these interactions are becoming a fundamental springboard for medical research in treatment and prevention.

We are soliciting articles on the regulation of the microbiome/microbiota against dysbiosis, and the management of certain diseases related to it. We are particularly interested in recent articles reporting on the relevance of biomolecular regulation mechanisms through various factors of host–microbiome interactions by inviting researchers to contribute original research papers and review articles that will help us understand these underlying molecular mechanisms for the development of potential discoveries and strategies for curing diseases from dysbiosis.

Dr. Ioannis Alexandros Charitos
Guest Editor

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Keywords

microbiome
dysbiosis
microbiology
immunity
cytokine/chemokine networks
microbiota axes pathways
toxic substances
autommunity

Related Special Issue

Microbiome and Metabolome in the Gastrointestinal Tract, 2nd Edition in International Journal of Molecular Sciences (5 articles)

Published Papers (10 papers)

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19 pages, 9922 KiB

Open AccessArticle

Fecal Microbiota Composition, Their Interactions, and Metagenome Function in US Adults with Type 2 Diabetes According to Enterotypes

by Sunmin Park, Ting Zhang and Suna Kang

Int. J. Mol. Sci. 2023, 24(11), 9533; https://doi.org/10.3390/ijms24119533 - 31 May 2023

Cited by 6 | Viewed by 1399

Abstract

T2DM etiology differs among Asians and Caucasians and may be associated with gut microbiota influenced by different diet patterns. However, the association between fecal bacterial composition, enterotypes, and T2DM susceptibility remained controversial. We investigated the fecal bacterial composition, co-abundance network, and metagenome function in US adults with T2DM compared to healthy adults based on enterotypes. We analyzed 1911 fecal bacterial files of 1039 T2DM and 872 healthy US adults from the Human Microbiome Projects. Operational taxonomic units were obtained after filtering and cleaning the files using Qiime2 tools. Machine learning and network analysis identified primary bacteria and their interactions influencing T2DM incidence, clustered into enterotypes, Bacteroidaceae (ET-B), Lachnospiraceae (ET-L), and Prevotellaceae (ET-P). ET-B showed higher T2DM incidence. Alpha-diversity was significantly lower in T2DM in ET-L and ET-P (p < 0.0001), but not in ET-B. Beta-diversity revealed a distinct separation between T2DM and healthy groups across all enterotypes (p < 0.0001). The XGBoost model exhibited high accuracy and sensitivity. Enterocloster bolteae, Facalicatena fissicatena, Clostridium symbiosum, and Facalibacterium prausnitizii were more abundant in the T2DM group than in the healthy group. Bacteroides koreensis, Oscillibacter ruminantium, Bacteroides uniformis, and Blautia wexlerae were lower in the T2DM than in the healthy group regardless of the enterotypes in the XGBoost model (p < 0.0001). However, the patterns of microbial interactions varied among different enterotypes affecting T2DM risk. The interaction between fecal bacteria was more tightly regulated in the ET-L than in the ET-B and ET-P groups (p < 0.001). Metagenomic analysis revealed an inverse association between bacteria abundance in T2DM, energy utility, butanoate and propanoate metabolism, and the insulin signaling pathway (p < 0.0001). In conclusion, fecal bacteria play a role in T2DM pathogenesis, particularly within different enterotypes, providing valuable insights into the link between gut microbiota and T2DM in the US population. Full article

(This article belongs to the Special Issue Microbiome and Metabolome in the Gastrointestinal Tract)

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18 pages, 3142 KiB

Open AccessArticle

Dietary Supplementation of Microbial Dextran and Inulin Exerts Hypocholesterolemic Effects and Modulates Gut Microbiota in BALB/c Mice Models

by Iqra Jawad, Husam Bin Tawseen, Muhammad Irfan, Waqar Ahmad, Mujtaba Hassan, Fazal Sattar, Fazli Rabbi Awan, Shazia Khaliq, Nasrin Akhtar, Kalsoom Akhtar, Munir Ahmad Anwar and Nayla Munawar

Int. J. Mol. Sci. 2023, 24(6), 5314; https://doi.org/10.3390/ijms24065314 - 10 Mar 2023

Cited by 1 | Viewed by 1964

Abstract

Microbial exopolysaccharides (EPSs), having great structural diversity, have gained tremendous interest for their prebiotic effects. In the present study, mice models were used to investigate if microbial dextran and inulin-type EPSs could also play role in the modulation of microbiomics and metabolomics by improving certain biochemical parameters, such as blood cholesterol and glucose levels and weight gain. Feeding the mice for 21 days on EPS-supplemented feed resulted in only 7.6 ± 0.8% weight gain in the inulin-fed mice group, while the dextran-fed group also showed a low weight gain trend as compared to the control group. Blood glucose levels of the dextran- and inulin-fed groups did not change significantly in comparison with the control where it increased by 22 ± 5%. Moreover, the dextran and inulin exerted pronounced hypocholesterolemic effects by reducing the serum cholesterol levels by 23% and 13%, respectively. The control group was found to be mainly populated with Enterococcus faecalis, Staphylococcus gallinarum, Mammaliicoccus lentus and Klebsiella aerogenes. The colonization of E. faecalis was inhibited by 59–65% while the intestinal release of Escherichia fergusonii was increased by 85–95% in the EPS-supplemented groups, respectively, along with the complete inhibition of growth of other enteropathogens. Additionally, higher populations of lactic acid bacteria were detected in the intestine of EPS-fed mice as compared to controls. Full article

(This article belongs to the Special Issue Microbiome and Metabolome in the Gastrointestinal Tract)

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21 pages, 2976 KiB

Open AccessArticle

Key Stratification of Microbiota Taxa and Metabolites in the Host Metabolic Health–Disease Balance

by Alfonso Torres-Sánchez, Alicia Ruiz-Rodríguez, Pilar Ortiz and Margarita Aguilera

Int. J. Mol. Sci. 2023, 24(5), 4519; https://doi.org/10.3390/ijms24054519 - 24 Feb 2023

Cited by 6 | Viewed by 1851

Abstract

Human gut microbiota seems to drive the interaction with host metabolism through microbial metabolites, enzymes, and bioactive compounds. These components determine the host health–disease balance. Recent metabolomics and combined metabolome–microbiome studies have helped to elucidate how these substances could differentially affect the individual host pathophysiology according to several factors and cumulative exposures, such as obesogenic xenobiotics. The present work aims to investigate and interpret newly compiled data from metabolomics and microbiota composition studies, comparing controls with patients suffering from metabolic-related diseases (diabetes, obesity, metabolic syndrome, liver and cardiovascular diseases, etc.). The results showed, first, a differential composition of the most represented genera in healthy individuals compared to patients with metabolic diseases. Second, the analysis of the metabolite counts exhibited a differential composition of bacterial genera in disease compared to health status. Third, qualitative metabolite analysis revealed relevant information about the chemical nature of metabolites related to disease and/or health status. Key microbial genera were commonly considered overrepresented in healthy individuals together with specific metabolites, e.g., Faecalibacterium and phosphatidylethanolamine; and the opposite, Escherichia and Phosphatidic Acid, which is converted into the intermediate Cytidine Diphosphate Diacylglycerol-diacylglycerol (CDP-DAG), were overrepresented in metabolic-related disease patients. However, it was not possible to associate most specific microbiota taxa and metabolites according to their increased and decreased profiles analyzed with health or disease. Interestingly, positive association of essential amino acids with the genera Bacteroides were observed in a cluster related to health, and conversely, benzene derivatives and lipidic metabolites were related to the genera Clostridium, Roseburia, Blautia, and Oscillibacter in a disease cluster. More studies are needed to elucidate the microbiota species and their corresponding metabolites that are key in promoting health or disease status. Moreover, we propose that greater attention should be paid to biliary acids and to microbiota–liver cometabolites and its detoxification enzymes and pathways. Full article

(This article belongs to the Special Issue Microbiome and Metabolome in the Gastrointestinal Tract)

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16 pages, 2233 KiB

Open AccessArticle

Altered Faecal Microbiota Composition and Structure of Ghanaian Children with Acute Gastroenteritis

by Emmanuel Kofi Quaye, Raymond Lovelace Adjei, Abiola Isawumi, David J. Allen, J. Gregory Caporaso and Osbourne Quaye

Int. J. Mol. Sci. 2023, 24(4), 3607; https://doi.org/10.3390/ijms24043607 - 10 Feb 2023

Cited by 4 | Viewed by 2290

Abstract

Acute gastroenteritis (AGE) is a disease of global public health importance. Recent studies show that children with AGE have an altered gut microbiota relative to non-AGE controls. Yet, how the gut microbiota differs in Ghanaian children with and without AGE remains unclear. Here, we explore the 16S rRNA gene-based faecal microbiota profiles of Ghanaian children five years of age and younger, comprising 57 AGE cases and 50 healthy controls. We found that AGE cases were associated with lower microbial diversity and altered microbial sequence profiles relative to the controls. The faecal microbiota of AGE cases was enriched for disease-associated bacterial genera, including Enterococcus, Streptococcus, and Staphylococcus. In contrast, the faecal microbiota of controls was enriched for potentially beneficial genera, including Faecalibacterium, Prevotella, Ruminococcus, and Bacteroides. Lastly, distinct microbial correlation network characteristics were observed between AGE cases and controls, thereby supporting broad differences in faecal microbiota structure. Altogether, we show that the faecal microbiota of Ghanaian children with AGE differ from controls and are enriched for bacterial genera increasingly associated with diseases. Full article

(This article belongs to the Special Issue Microbiome and Metabolome in the Gastrointestinal Tract)

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21 pages, 7065 KiB

Open AccessArticle

Poria cocos Polysaccharide Ameliorated Antibiotic-Associated Diarrhea in Mice via Regulating the Homeostasis of the Gut Microbiota and Intestinal Mucosal Barrier

by Huachong Xu, Shiqi Wang, Yawen Jiang, Jialin Wu, Lili Chen, Yujia Ding, Yingtong Zhou, Li Deng and Xiaoyin Chen

Int. J. Mol. Sci. 2023, 24(2), 1423; https://doi.org/10.3390/ijms24021423 - 11 Jan 2023

Cited by 13 | Viewed by 2738

Abstract

Poria cocos polysaccharides (PCP) have been validated for several biological activities, including antitumor, anti-inflammatory, antioxidant, immunomodulatory, hepatoprotective and modulation on gut microbiota. In this research, we aim to demonstrate the potential prebiotic effects and the therapeutic efficacies of PCP in the treatment of antibiotic-associated diarrhea (AAD), and confirm the beneficial effects of PCP on gut dysbiosis. Antibiotic-associated diarrhea mice models were established by treating them with broad-spectrum antibiotics in drinking water for seven days. Mice in two groups treated with probiotics and polysaccharide were given Bifico capsules (4.2 g/kg/d) and PCP (250 mg/kg/d) for seven days using intragastric gavage, respectively. To observe the regulatory effects of PCP on gut microbiota and intestinal mucosal barrier, we conducted the following experiments: intestinal flora analysis (16S rDNA sequencing), histology (H&E staining) and tight junction proteins (immunofluorescence staining). The levels of mRNA expression of receptors associated with inflammation and gut metabolism were assessed by real-time reverse transcription-polymerase chain reaction (RT-PCR). The study revealed that PCP can comprehensively improve the clinical symptoms of AAD mice, including fecal traits, mental state, hair quality, etc., similar to the effect of probiotics. Based on histology observation, PCP significantly improved the substantial structure of the intestine of AAD mice by increasing the expression levels of colonic tight junction protein zonula-occludens 1 (ZO-1) and its mRNA. Moreover, PCP not only increased the abundance of gut microbiota, but also increased the diversity of gut microbiota in AAD mice, including alpha diversity and beta diversity. Further analysis found that PCP can modulate seven characteristic species of intestinal flora in AAD mice, including Parabacteroides_distasonis, Akkermansia_muciniphila, Clostridium_saccharolyticum, Ruminoc-occus_gnavus, Lactobacillus_salivarius, Salmonella_enterica and Mucispirillum_schaedleri. Finally, enrichment analysis predicted that PCP may affect intestinal mucosal barrier function, host immune response and metabolic function by regulating the microbiota. RT-PCR experiments showed that PCP can participate in immunomodulatory and modulation on metabolic by regulating the mRNA expression of forkhead-box protein 3 (FOXP3) and G protein-coupled receptor 41 (GPR41). These results indicated that Poria cocos polysaccharide may ameliorate antibiotic-associated diarrhea in mice by regulating the homeostasis of the gut microbiota and intestinal mucosal barrier. In addition, polysaccharide-derived changes in intestinal microbiota were involved in the immunomodulatory activities and modulation of the metabolism. Full article

(This article belongs to the Special Issue Microbiome and Metabolome in the Gastrointestinal Tract)

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11 pages, 1543 KiB

Open AccessArticle

Molecular Research of Lipid Peroxidation and Antioxidant Enzyme Activity of Comamonas testosteroni Bacterial Cells under the Hexachlorobenzene Impact

by Mariia Dimova, Andrii Tugai, Tetiana Tugai, Galyna Iutynska, Dani Dordevic and Ivan Kushkevych

Int. J. Mol. Sci. 2022, 23(19), 11415; https://doi.org/10.3390/ijms231911415 - 27 Sep 2022

Cited by 6 | Viewed by 1574

Abstract

The species of Comamonas testosteroni is the most common human pathogen of the genus, which can be associated with acute appendicitis, infections of the bloodstream, the peritoneal cavity, cerebrospinal fluid, inflammatory bowel disease, and in general, bacteremia. According to the literature, Comamonas testosteroni has destructive activity to a wide range of toxic chemical compounds, including chlorobenzenes. The specified strains were isolated from the soil of the organochlorine waste landfill, where hexachlorobenzene (HCB) was predominant. These strains were expected to be capable of degrading HCB. Microbiological (bacterial enrichment and cultivating, bacterial biomass obtaining), molecular biology, biochemical (enzymatic activities, malondialdehyde measuring, peroxidation lipid products measuring), and statistical methods were carried out in this research. The reaction of both strains (UCM B-400 and UCM B-401) to the hexachlorobenzene presence differed in the content of diene and triene conjugates and malondialdehyde, as well as different catalase and peroxidase activity levels. In terms of primary peroxidation products, diene conjugates were lower, except conditions with 20 mg/L HCB, where these were higher up to two times, than the pure control. Malondialdehyde in strain B-400 cells decreased up to five times, in B-401, but increased up to two times, compared to the pure control. Schiff bases in strain B-400 cells were 2–3 times lower than the pure control. However, in B-401 cells Schiff bases under higher HCB dose were in the same level with the pure control. Catalase activity was 1.5 times higher in all experimental variants, compared to the pure control (in the strain B-401 cells), but in the B-400 strain, cells were 2 times lower, compared to the pure control. The response of the two strains to hexachlorobenzene was similar only in peroxidase activity terms, which was slightly higher compared to the pure control. The physiological response of Comamonas testosteroni strains to hexachlorobenzene has a typical strain reaction. The physiological response level of these strains to hexachlorobenzene confirms its tolerance, and indirectly, the ability to destroy the specified toxic compound. Full article

(This article belongs to the Special Issue Microbiome and Metabolome in the Gastrointestinal Tract)

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Review

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18 pages, 351 KiB

Open AccessReview

Dysbiotic Gut Microbiota-Derived Metabolites and Their Role in Non-Communicable Diseases

by Jian Tan, Jemma Taitz, Ralph Nanan, Georges Grau and Laurence Macia

Int. J. Mol. Sci. 2023, 24(20), 15256; https://doi.org/10.3390/ijms242015256 - 17 Oct 2023

Cited by 2 | Viewed by 1587

Abstract

Dysbiosis, generally defined as the disruption to gut microbiota composition or function, is observed in most diseases, including allergies, cancer, metabolic diseases, neurological disorders and diseases associated with autoimmunity. Dysbiosis is commonly associated with reduced levels of beneficial gut microbiota-derived metabolites such as short-chain fatty acids (SCFA) and indoles. Supplementation with these beneficial metabolites, or interventions to increase their microbial production, has been shown to ameliorate a variety of inflammatory diseases. Conversely, the production of gut ‘dysbiotic’ metabolites or by-products by the gut microbiota may contribute to disease development. This review summarizes the various ‘dysbiotic’ gut-derived products observed in cardiovascular diseases, cancer, inflammatory bowel disease, metabolic diseases including non-alcoholic steatohepatitis and autoimmune disorders such as multiple sclerosis. The increased production of dysbiotic gut microbial products, including trimethylamine, hydrogen sulphide, products of amino acid metabolism such as p-Cresyl sulphate and phenylacetic acid, and secondary bile acids such as deoxycholic acid, is commonly observed across multiple diseases. The simultaneous increased production of dysbiotic metabolites with the impaired production of beneficial metabolites, commonly associated with a modern lifestyle, may partially explain the high prevalence of inflammatory diseases in western countries. Full article

(This article belongs to the Special Issue Microbiome and Metabolome in the Gastrointestinal Tract)

32 pages, 3789 KiB

Open AccessReview

The Crosstalk between Gut Microbiota and Nervous System: A Bidirectional Interaction between Microorganisms and Metabolome

by Monica Montagnani, Lucrezia Bottalico, Maria Assunta Potenza, Ioannis Alexandros Charitos, Skender Topi, Marica Colella and Luigi Santacroce

Int. J. Mol. Sci. 2023, 24(12), 10322; https://doi.org/10.3390/ijms241210322 - 19 Jun 2023

Cited by 17 | Viewed by 4417

Abstract

Several studies have shown that the gut microbiota influences behavior and, in turn, changes in the immune system associated with symptoms of depression or anxiety disorder may be mirrored by corresponding changes in the gut microbiota. Although the composition/function of the intestinal microbiota appears to affect the central nervous system (CNS) activities through multiple mechanisms, accurate epidemiological evidence that clearly explains the connection between the CNS pathology and the intestinal dysbiosis is not yet available. The enteric nervous system (ENS) is a separate branch of the autonomic nervous system (ANS) and the largest part of the peripheral nervous system (PNS). It is composed of a vast and complex network of neurons which communicate via several neuromodulators and neurotransmitters, like those found in the CNS. Interestingly, despite its tight connections to both the PNS and ANS, the ENS is also capable of some independent activities. This concept, together with the suggested role played by intestinal microorganisms and the metabolome in the onset and progression of CNS neurological (neurodegenerative, autoimmune) and psychopathological (depression, anxiety disorders, autism) diseases, explains the large number of investigations exploring the functional role and the physiopathological implications of the gut microbiota/brain axis. Full article

(This article belongs to the Special Issue Microbiome and Metabolome in the Gastrointestinal Tract)

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13 pages, 1057 KiB

Open AccessReview

Inflammatory Bowel Diseases and Gut Microbiota

by Yuri Haneishi, Yuma Furuya, Mayu Hasegawa, Antonio Picarelli, Mauro Rossi and Junki Miyamoto

Int. J. Mol. Sci. 2023, 24(4), 3817; https://doi.org/10.3390/ijms24043817 - 14 Feb 2023

Cited by 30 | Viewed by 5442

Abstract

Inflammatory bowel disease (IBD) is an inflammatory disease of the gastrointestinal tract, the incidence of which has rapidly increased worldwide, especially in developing and Western countries. Recent research has suggested that genetic factors, the environment, microbiota, and immune responses are involved in the pathogenesis; however, the underlying causes of IBD are unclear. Recently, gut microbiota dysbiosis, especially a decrease in the abundance and diversity of specific genera, has been suggested as a trigger for IBD-initiating events. Improving the gut microbiota and identifying the specific bacterial species in IBD are essential for understanding the pathogenesis and treatment of IBD and autoimmune diseases. Here, we review the different aspects of the role played by gut microbiota in the pathogenesis of IBD and provide a theoretical basis for modulating gut microbiota through probiotics, fecal microbiota transplantation, and microbial metabolites. Full article

(This article belongs to the Special Issue Microbiome and Metabolome in the Gastrointestinal Tract)

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55 pages, 1025 KiB

Open AccessReview

Necrotizing Enterocolitis: The Role of Hypoxia, Gut Microbiome, and Microbial Metabolites

by Aleksandra Kaplina, Svetlana Kononova, Ekaterina Zaikova, Tatiana Pervunina, Natalia Petrova and Stanislav Sitkin

Int. J. Mol. Sci. 2023, 24(3), 2471; https://doi.org/10.3390/ijms24032471 - 27 Jan 2023

Cited by 8 | Viewed by 3777

Abstract

Necrotizing enterocolitis (NEC) is a life-threatening disease that predominantly affects very low birth weight preterm infants. Development of NEC in preterm infants is accompanied by high mortality. Surgical treatment of NEC can be complicated by short bowel syndrome, intestinal failure, parenteral nutrition-associated liver disease, and neurodevelopmental delay. Issues surrounding pathogenesis, prevention, and treatment of NEC remain unclear. This review summarizes data on prenatal risk factors for NEC, the role of pre-eclampsia, and intrauterine growth retardation in the pathogenesis of NEC. The role of hypoxia in NEC is discussed. Recent data on the role of the intestinal microbiome in the development of NEC, and features of the metabolome that can serve as potential biomarkers, are presented. The Pseudomonadota phylum is known to be associated with NEC in preterm neonates, and the role of other bacteria and their metabolites in NEC pathogenesis is also discussed. The most promising approaches for preventing and treating NEC are summarized. Full article

(This article belongs to the Special Issue Microbiome and Metabolome in the Gastrointestinal Tract)

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