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Gut Microbiota in Gastroenterology and Hepatology

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 (31 October 2022) | Viewed by 48861

Special Issue Editor


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Guest Editor
Graduate Institute of Traditional Chinese Medicine, Chang Gung University, 259 Wen-Hwa 1st Road, Kweishan, Taoyuan 333, Taiwan
Interests: hepatology; microbiome; geriatric medicine; sarcopenia; neuromuscular diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

The microbiome consists of microbes that are both helpful and potentially harmful. The gut microbiota contributes substantially to circulating metabolites in the context of liver diseases. The intestinal microbiota may contribute to the high prevalence of metabolic disorders of the human host and, when aberrant, to the pathogenesis of various common metabolic disorders including obesity, cardio-metabolic diseases, type 2 diabetes, non-alcoholic liver disease, inflammatory bowel disease, colorectal cancer, and malnutrition.

This Special Issue aims to highlight examples of microbiota-based therapies to improve metabolic health and outline potential avenues for future epidemiological and experimental studies. All efforts are under way to provide functional insights into the gut microbiota and its mechanisms of action, accelerate our understanding of the role of the microbiota beyond the gut, and develop microbiota-based strategies so that the microbiome can be applicated in the clinic.

This Special Issue is now open to receive manuscripts on all aspects of gut microbiota with particular emphasis on gastroenterology and hepatology.

Dr. Tzung-Yan Lee
Guest Editor

Manuscript Submission Information

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Keywords

  • gut microbiota
  • hepatology
  • gastroenterology
  • inflammatory bowel disease
  • colorectal cancer
  • nutrition
  • nature products

Published Papers (14 papers)

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17 pages, 4438 KiB  
Article
Gut Microbial Perturbation and Host Response Induce Redox Pathway Upregulation along the Gut–Liver Axis during Giardiasis in C57BL/6J Mouse Model
by Avinash V. Karpe, Melanie L. Hutton, Steven J. Mileto, Meagan L. James, Chris Evans, Amol B. Ghodke, Rohan M. Shah, Suzanne S. Metcalfe, Jian-Wei Liu, Tom Walsh, Dena Lyras, Enzo A. Palombo and David J. Beale
Int. J. Mol. Sci. 2023, 24(2), 1636; https://doi.org/10.3390/ijms24021636 - 13 Jan 2023
Cited by 2 | Viewed by 2337
Abstract
Apicomplexan infections, such as giardiasis and cryptosporidiosis, negatively impact a considerable proportion of human and commercial livestock populations. Despite this, the molecular mechanisms of disease, particularly the effect on the body beyond the gastrointestinal tract, are still poorly understood. To highlight host–parasite–microbiome biochemical [...] Read more.
Apicomplexan infections, such as giardiasis and cryptosporidiosis, negatively impact a considerable proportion of human and commercial livestock populations. Despite this, the molecular mechanisms of disease, particularly the effect on the body beyond the gastrointestinal tract, are still poorly understood. To highlight host–parasite–microbiome biochemical interactions, we utilised integrated metabolomics-16S rRNA genomics and metabolomics–proteomics approaches in a C57BL/6J mouse model of giardiasis and compared these to Cryptosporidium and uropathogenic Escherichia coli (UPEC) infections. Comprehensive samples (faeces, blood, liver, and luminal contents from duodenum, jejunum, ileum, caecum and colon) were collected 10 days post infection and subjected to proteome and metabolome analysis by liquid and gas chromatography–mass spectrometry, respectively. Microbial populations in faeces and luminal washes were examined using 16S rRNA metagenomics. Proteome–metabolome analyses indicated that 12 and 16 key pathways were significantly altered in the gut and liver, respectively, during giardiasis with respect to other infections. Energy pathways including glycolysis and supporting pathways of glyoxylate and dicarboxylate metabolism, and the redox pathway of glutathione metabolism, were upregulated in small intestinal luminal contents and the liver during giardiasis. Metabolomics-16S rRNA genetics integration indicated that populations of three bacterial families—Autopobiaceae (Up), Desulfovibrionaceae (Up), and Akkermanasiaceae (Down)—were most significantly affected across the gut during giardiasis, causing upregulated glycolysis and short-chained fatty acid (SCFA) metabolism. In particular, the perturbed Akkermanasiaceae population seemed to cause oxidative stress responses along the gut–liver axis. Overall, the systems biology approach applied in this study highlighted that the effects of host–parasite–microbiome biochemical interactions extended beyond the gut ecosystem to the gut–liver axis. These findings form the first steps in a comprehensive comparison to ascertain the major molecular and biochemical contributors of host–parasite interactions and contribute towards the development of biomarker discovery and precision health solutions for apicomplexan infections. Full article
(This article belongs to the Special Issue Gut Microbiota in Gastroenterology and Hepatology)
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18 pages, 5408 KiB  
Article
Proton Pump Inhibitor Pantoprazole Modulates Intestinal Microbiota and Induces TLR4 Signaling and Fibrosis in Mouse Liver
by Heloisa B. Assalin, Kelly Cristiane Gabriel De Almeida, Dioze Guadagnini, Andrey Santos, Caio J. Teixeira, Silvana Bordin, Guilherme Z. Rocha and Mario J. A. Saad
Int. J. Mol. Sci. 2022, 23(22), 13766; https://doi.org/10.3390/ijms232213766 - 09 Nov 2022
Cited by 1 | Viewed by 3551
Abstract
Proton pump inhibitors (PPIs) are one of the most prescribed drugs around the world. PPIs induce microbiota modulation such as obesity both in humans and in animal models. However, since PPIs can induce microbiota modulation despite the absence of a high-fat diet or [...] Read more.
Proton pump inhibitors (PPIs) are one of the most prescribed drugs around the world. PPIs induce microbiota modulation such as obesity both in humans and in animal models. However, since PPIs can induce microbiota modulation despite the absence of a high-fat diet or weight gain, it is an interesting model to correlate microbiota modulation with the establishment of non-alcoholic fatty liver disease (NAFLD). We investigated the effect of pantoprazole treatment on TLR4 signaling and liver histology in C57BL/6J mice for 60 days, trying to correlate microbiota modulation with some aspects of liver injury. We performed glucose (GTT) and insulin (ITT) tolerance tests, serum lipopolysaccharide (LPS) dosage, liver histology, liver and intestine extraction for Western blot and qPCR. Fecal microbiota were investigated via metagenomics. Chronic treatment with pantoprazole induced microbiota modulation and impaired ileum barrier integrity, without an association with insulin resistance. Furthermore, increased circulating LPS and increased Toll-like receptor 4 (TLR4) and TGFβ downstream signaling may have an important role in the development of the observed liver microvesicular steatosis and fibrosis. Finally, this model of PPI-induced changes in microbiota might be useful to investigate liver microvesicular steatosis and fibrosis. Full article
(This article belongs to the Special Issue Gut Microbiota in Gastroenterology and Hepatology)
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20 pages, 1864 KiB  
Article
Prenatal Maternal Antibiotics Treatment Alters the Gut Microbiota and Immune Function of Post-Weaned Prepubescent Offspring
by Abdullah M. Madany, Heather K. Hughes and Paul Ashwood
Int. J. Mol. Sci. 2022, 23(21), 12879; https://doi.org/10.3390/ijms232112879 - 25 Oct 2022
Cited by 5 | Viewed by 1609
Abstract
This study aimed to investigate the immediate and continual perturbation to the gut microbiota of offspring in the weeks post-weaning and how these may be modulated by treating pregnant C57BL/6J dams with antibiotics (ABX). We used a broad-spectrum antibiotic cocktail consisting of ampicillin [...] Read more.
This study aimed to investigate the immediate and continual perturbation to the gut microbiota of offspring in the weeks post-weaning and how these may be modulated by treating pregnant C57BL/6J dams with antibiotics (ABX). We used a broad-spectrum antibiotic cocktail consisting of ampicillin 1 mg/mL, neomycin 1 mg/mL, and vancomycin 0.5 mg/mL, or vancomycin 0.5 mg/mL alone, administered ad-lib orally to dams via drinking water during gestation and stopped after delivery. We analyzed the gut microbiota of offspring, cytokine profiles in circulation, and the brain to determine if there was evidence of a gut-immune-brain connection. Computationally predicted metabolic pathways were calculated from 16s rRNA sequencing data. ABX treatment can negatively affect the gut microbiota, including reduced diversity, altered metabolic activity, and immune function. We show that the maternal ABX-treatment continues to alter the offspring’s gut microbiota diversity, composition, and metabolic pathways after weaning, with the most significant differences evident in 5-week-olds as opposed to 4-week-olds. Lower levels of chemokines and inflammatory cytokines, such as interleukin (IL)-1α and IL-2, are also seen in the periphery and brains of offspring, respectively. In conclusion, this study shows maternal antibiotic administration alters gut microbiome profiles in offspring, which undergoes a continuous transformation, from week to week, at an early age after weaning. Full article
(This article belongs to the Special Issue Gut Microbiota in Gastroenterology and Hepatology)
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19 pages, 2924 KiB  
Article
Effects of Cigarette Smoke Exposure on the Gut Microbiota and Liver Transcriptome in Mice Reveal Gut–Liver Interactions
by Lei Meng, Mengjun Xu, Youwen Xing, Chen Chen, Jiandong Jiang and Xihui Xu
Int. J. Mol. Sci. 2022, 23(19), 11008; https://doi.org/10.3390/ijms231911008 - 20 Sep 2022
Cited by 5 | Viewed by 2090
Abstract
Cigarette smoke exposure has a harmful impact on health and increases the risk of disease. However, studies on cigarette-smoke-induced adverse effects from the perspective of the gut–liver axis are lacking. In this study, we evaluated the adverse effects of cigarette smoke exposure on [...] Read more.
Cigarette smoke exposure has a harmful impact on health and increases the risk of disease. However, studies on cigarette-smoke-induced adverse effects from the perspective of the gut–liver axis are lacking. In this study, we evaluated the adverse effects of cigarette smoke exposure on mice through physiological, biochemical, and histopathological analyses and explored cigarette-smoke-induced gut microbiota imbalance and changes in liver gene expression through a multiomics analysis. We demonstrated that cigarette smoke exposure caused abnormal physiological indices (including reduced body weight, blood lipids, and food intake) in mice, which also triggered liver injury and induced disorders of the gut microbiota and liver transcriptome (especially lipid metabolism). A significant correlation between intestinal bacterial abundance and the expression of lipid-metabolism-related genes was detected, suggesting the coordinated regulation of lipid metabolism by gut microbiota and liver metabolism. Specifically, Salmonella (harmful bacterium) was negatively and positively correlated with up- (such as Acsl3 and Me1) and downregulated genes (such as Angptl4, Cyp4a12a, and Plin5) involved in lipid metabolism, while Ligilactobacillus (beneficial bacterium) showed opposite trends with these genes. Our results clarified the key role of gut microbiota in liver damage and metabolism and improved the understanding of gut–liver interactions caused by cigarette smoke exposure. Full article
(This article belongs to the Special Issue Gut Microbiota in Gastroenterology and Hepatology)
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21 pages, 7566 KiB  
Article
Depletion of Gut Microbiota Inhibits Hepatic Lipid Accumulation in High-Fat Diet-Fed Mice
by Hui Han, Mengyu Wang, Ruqing Zhong, Bao Yi, Martine Schroyen and Hongfu Zhang
Int. J. Mol. Sci. 2022, 23(16), 9350; https://doi.org/10.3390/ijms23169350 - 19 Aug 2022
Cited by 11 | Viewed by 2805
Abstract
Dysregulated lipid metabolism is a key pathology in metabolic diseases and the liver is a critical organ for lipid metabolism. The gut microbiota has been shown to regulate hepatic lipid metabolism in the host. However, the underlying mechanism by which the gut microbiota [...] Read more.
Dysregulated lipid metabolism is a key pathology in metabolic diseases and the liver is a critical organ for lipid metabolism. The gut microbiota has been shown to regulate hepatic lipid metabolism in the host. However, the underlying mechanism by which the gut microbiota influences hepatic lipid metabolism has not been elucidated. Here, a gut microbiota depletion mouse model was constructed with an antibiotics cocktail (Abx) to study the mechanism through which intestinal microbiota regulates hepatic lipid metabolism in high-fat diet (HFD)-fed mice. Our results showed that the Abx treatment effectively eradicated the gut microbiota in these mice. Microbiota depletion reduced the body weight and fat deposition both in white adipose tissue and liver. In addition, microbiota depletion reduced serum levels of glucose, total cholesterol (TC), low-density lipoproteins (LDL), insulin, and leptin in HFD-fed mice. Importantly, the depletion of gut microbiota in HFD-fed mice inhibited excessive hepatic lipid accumulation. Mechanistically, RNA-seq results revealed that gut microbiota depletion changed the expression of hepatic genes involved in cholesterol and fatty acid metabolism, such as Cd36, Mogat1, Cyp39a1, Abcc3, and Gpat3. Moreover, gut microbiota depletion reduced the abundance of bacteria associated with abnormal metabolism and inflammation, including Lachnospiraceae, Coriobacteriaceae_UCG-002, Enterorhabdus, Faecalibaculum, and Desulfovibrio. Correlation analysis showed that there was strong association between the altered gut microbiota abundance and the serum cholesterol level. This study indicates that gut microbiota ameliorates HFD-induced hepatic lipid metabolic dysfunction, which might be associated with genes participating in cholesterol and fatty acid metabolism in the liver. Full article
(This article belongs to the Special Issue Gut Microbiota in Gastroenterology and Hepatology)
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21 pages, 2311 KiB  
Article
Effects of the Lipid Profile, Type 2 Diabetes and Medication on the Metabolic Syndrome—Associated Gut Microbiome
by Gratiela Gradisteanu Pircalabioru, Janie Liaw, Ozan Gundogdu, Nicolae Corcionivoschi, Iuliana Ilie, Luciana Oprea, Madalina Musat and Mariana-Carmen Chifiriuc
Int. J. Mol. Sci. 2022, 23(14), 7509; https://doi.org/10.3390/ijms23147509 - 06 Jul 2022
Cited by 9 | Viewed by 2355
Abstract
Metabolic syndrome (MetSyn) is a major health problem affecting approximately 25% of the worldwide population. Since the gut microbiota is highly connected to the host metabolism, several recent studies have emerged to characterize the role of the microbiome in MetSyn development and progression. [...] Read more.
Metabolic syndrome (MetSyn) is a major health problem affecting approximately 25% of the worldwide population. Since the gut microbiota is highly connected to the host metabolism, several recent studies have emerged to characterize the role of the microbiome in MetSyn development and progression. To this end, our study aimed to identify the microbiome patterns which distinguish MetSyn from type 2 diabetes mellitus (T2DM). We performed 16S rRNA amplicon sequencing on a cohort of 70 individuals among which 40 were MetSyn patients. The microbiome of MetSyn patients was characterised by reduced diversity, loss of butyrate producers (Subdoligranulum, Butyricicoccus, Faecalibacterium prausnitzii) and enrichment in the relative abundance of fungal populations. We also show a link between the gut microbiome and lipid metabolism in MetSyn. Specifically, low-density lipoproteins (LDL) and high-density lipoproteins (HDL) display a positive effect on gut microbial diversity. When interrogating the signature of gut microbiota in a subgroup of patients harbouring both MetSyn and T2DM conditions, we observed a significant increase in taxa such as Bacteroides, Clostridiales, and Erysipelotrichaceae. This preliminary study shows for the first time that T2DM brings unique signatures of gut microbiota in MetSyn patients. We also highlight the impact of metformin treatment on the gut microbiota. Metformin administration was linked to changes in Prevotellaceae, Rickenellaceae, and Clostridiales. Further research focusing on the microbiome-metabolome patterns is needed to clarify the exact association of various gut microbial communities with the progression of T2DM and the occurrence of various complications in MetSyn patients. Full article
(This article belongs to the Special Issue Gut Microbiota in Gastroenterology and Hepatology)
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29 pages, 5058 KiB  
Article
The Combination of Intestinal Alkaline Phosphatase Treatment with Moderate Physical Activity Alleviates the Severity of Experimental Colitis in Obese Mice via Modulation of Gut Microbiota, Attenuation of Proinflammatory Cytokines, Oxidative Stress Biomarkers and DNA Oxidative Damage in Colonic Mucosa
by Dagmara Wojcik-Grzybek, Magdalena Hubalewska-Mazgaj, Marcin Surmiak, Zbigniew Sliwowski, Anna Dobrut, Agata Mlodzinska, Adrianna Wojcik, Slawomir Kwiecien, Marcin Magierowski, Agnieszka Mazur-Bialy, Jan Bilski and Tomasz Brzozowski
Int. J. Mol. Sci. 2022, 23(6), 2964; https://doi.org/10.3390/ijms23062964 - 09 Mar 2022
Cited by 6 | Viewed by 4026
Abstract
Inflammatory bowel diseases (IBD) are commonly considered as Crohn’s disease and ulcerative colitis, but the possibility that the alterations in gut microbiota and oxidative stress may affect the course of experimental colitis in obese physically exercising mice treated with the intestinal alkaline phosphatase [...] Read more.
Inflammatory bowel diseases (IBD) are commonly considered as Crohn’s disease and ulcerative colitis, but the possibility that the alterations in gut microbiota and oxidative stress may affect the course of experimental colitis in obese physically exercising mice treated with the intestinal alkaline phosphatase (IAP) has been little elucidated. Mice fed a high-fat-diet (HFD) or normal diet (ND) for 14 weeks were randomly assigned to exercise on spinning wheels (SW) for 7 weeks and treated with IAP followed by intrarectal administration of TNBS. The disease activity index (DAI), grip muscle strength test, oxidative stress biomarkers (MDA, SOD, GSH), DNA damage (8-OHdG), the plasma levels of cytokines IL-2, IL-6, IL-10, IL-12p70, IL-17a, TNF-α, MCP-1 and leptin were assessed, and the stool composition of the intestinal microbiota was determined by next generation sequencing (NGS). The TNBS-induced colitis was worsened in obese sedentary mice as manifested by severe colonic damage, an increase in DAI, oxidative stress biomarkers, DNA damage and decreased muscle strength. The longer running distance and weight loss was observed in mice given IAP or subjected to IAP + SW compared to sedentary ones. Less heterogeneous microbial composition was noticed in sedentary obese colitis mice and this effect disappeared in IAP + SW mice. Absence of Alistipes, lower proportion of Turicibacter, Proteobacteria and Faecalibacterium, an increase in Firmicutes and Clostridium, a decrease in oxidative stress biomarkers, 8-OHdG content and proinflammatory cytokines were observed in IAP + SW mice. IAP supplementation in combination with moderate physical activity attenuates the severity of murine colitis complicated by obesity through a mechanism involving the downregulation of the intestinal cytokine/chemokine network and oxidative stress, the modulation of the gut microbiota and an improvement of muscle strength. Full article
(This article belongs to the Special Issue Gut Microbiota in Gastroenterology and Hepatology)
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24 pages, 17826 KiB  
Article
Modulation of Gut Microbiota Combined with Upregulation of Intestinal Tight Junction Explains Anti-Inflammatory Effect of Corylin on Colitis-Associated Cancer in Mice
by Zi-Yu Chang, Hsuan-Miao Liu, Yann-Lii Leu, Chung-Hua Hsu and Tzung-Yan Lee
Int. J. Mol. Sci. 2022, 23(5), 2667; https://doi.org/10.3390/ijms23052667 - 28 Feb 2022
Cited by 29 | Viewed by 4891
Abstract
Inflammatory bowel disease (IBD) involves chronic inflammation, loss of epithelial integrity, and gastrointestinal microbiota dysbiosis, resulting in the development of a colon cancer known as colitis-associated colorectal cancer (CAC). In this study, we evaluated the effects of corylin in a mouse model of [...] Read more.
Inflammatory bowel disease (IBD) involves chronic inflammation, loss of epithelial integrity, and gastrointestinal microbiota dysbiosis, resulting in the development of a colon cancer known as colitis-associated colorectal cancer (CAC). In this study, we evaluated the effects of corylin in a mouse model of dextran sodium sulfate (DSS)-induced colitis. The results showed corylin could improved the survival rate and colon length, maintained body weight, and ameliorated the inflammatory response in the colon. Then, we further identified the possible antitumor effects after 30-day treatment of corylin on an azoxymethane (AOM)/DSS-induced CAC mouse model. Biomarkers associated with inflammation, the colon tissue barrier, macrophage polarization (CD11c, CCR7, CD163, and CD206), and microbiota dysbiosis were monitored in the AOM/DSS group versus corylin groups. Corylin downregulated pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β, and IL-6) mRNA expression and inflammatory signaling-associated markers (TLR4, MyD88, AP-1, CD11b, and F4/80). In addition, a colon barrier experiment revealed that epithelial cell proliferation of the mucus layer (Lgr5, Cyclin D1, and Olfm4) was downregulated and tight junction proteins (claudin-1 and ZO-1) were upregulated. Furthermore, the Firmicutes/Bacteroidetes ratio changed with corylin intervention, and the microbial diversity and community richness of the AOM/DSS mice were improved by corylin. The comparative analysis of gut microbiota revealed that Bacteroidetes, Patescibacteria, Candidatus Saccharimonas, Erysipelatoclostridium, and Enterorhabdus were significantly increased but Firmicutes, Turicibacter, Romboutsia, and Blautia decreased after corylin treatment. Altogether, corylin administration showed cancer-ameliorating effects by reducing the risk of colitis-associated colon cancer via regulation of inflammation, carcinogenesis, and compositional change of gut microbiota. Therefore, corylin could be a novel, potential health-protective, natural agent against CAC. Full article
(This article belongs to the Special Issue Gut Microbiota in Gastroenterology and Hepatology)
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Review

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21 pages, 2662 KiB  
Review
Fecal Microbiota Composition as a Metagenomic Biomarker of Dietary Intake
by Nathalia Caroline de Oliveira Melo, Amanda Cuevas-Sierra, Edwin Fernández-Cruz, Victor de la O and José Alfredo Martínez
Int. J. Mol. Sci. 2023, 24(5), 4918; https://doi.org/10.3390/ijms24054918 - 03 Mar 2023
Cited by 1 | Viewed by 2186
Abstract
Gut microbiota encompasses the set of microorganisms that colonize the gastrointestinal tract with mutual relationships that are key for host homeostasis. Increasing evidence supports cross intercommunication between the intestinal microbiome and the eubiosis–dysbiosis binomial, indicating a networking role of gut bacteria as potential [...] Read more.
Gut microbiota encompasses the set of microorganisms that colonize the gastrointestinal tract with mutual relationships that are key for host homeostasis. Increasing evidence supports cross intercommunication between the intestinal microbiome and the eubiosis–dysbiosis binomial, indicating a networking role of gut bacteria as potential metabolic health surrogate markers. The abundance and diversity of the fecal microbial community are already recognized to be associated with several disorders, such as obesity, cardiometabolic events, gastrointestinal alterations, and mental diseases, which suggests that intestinal microbes may be a valuable tool as causal or as consequence biomarkers. In this context, the fecal microbiota could also be used as an adequate and informative proxy of the nutritional composition of the food intake and about the adherence to dietary patterns, such as the Mediterranean or Western diets, by displaying specific fecal microbiome signatures. The aim of this review was to discuss the potential use of gut microbial composition as a putative biomarker of food intake and to screen the sensitivity value of fecal microbiota in the evaluation of dietary interventions as a reliable and precise alternative to subjective questionnaires. Full article
(This article belongs to the Special Issue Gut Microbiota in Gastroenterology and Hepatology)
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14 pages, 1523 KiB  
Review
Fecal Metagenomics and Metabolomics Identifying Microbial Signatures in Non-Alcoholic Fatty Liver Disease
by Satu Pekkala
Int. J. Mol. Sci. 2023, 24(5), 4855; https://doi.org/10.3390/ijms24054855 - 02 Mar 2023
Cited by 6 | Viewed by 2959
Abstract
The frequency of non-alcoholic fatty liver disease (NAFLD) has intensified, creating diagnostic challenges and increasing the need for reliable non-invasive diagnostic tools. Due to the importance of the gut–liver axis in the progression of NAFLD, studies attempt to reveal microbial signatures in NAFLD, [...] Read more.
The frequency of non-alcoholic fatty liver disease (NAFLD) has intensified, creating diagnostic challenges and increasing the need for reliable non-invasive diagnostic tools. Due to the importance of the gut–liver axis in the progression of NAFLD, studies attempt to reveal microbial signatures in NAFLD, evaluate them as diagnostic biomarkers, and to predict disease progression. The gut microbiome affects human physiology by processing the ingested food into bioactive metabolites. These molecules can penetrate the portal vein and the liver to promote or prevent hepatic fat accumulation. Here, the findings of human fecal metagenomic and metabolomic studies relating to NAFLD are reviewed. The studies present mostly distinct, and even contradictory, findings regarding microbial metabolites and functional genes in NAFLD. The most abundantly reproducing microbial biomarkers include increased lipopolysaccharides and peptidoglycan biosynthesis, enhanced degradation of lysine, increased levels of branched chain amino acids, as well as altered lipid and carbohydrate metabolism. Among other causes, the discrepancies between the studies may be related to the obesity status of the patients and the severity of NAFLD. In none of the studies, except for one, was diet considered, although it is an important factor driving gut microbiota metabolism. Future studies should consider diet in these analyses. Full article
(This article belongs to the Special Issue Gut Microbiota in Gastroenterology and Hepatology)
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18 pages, 907 KiB  
Review
The Role of the Gut Microbiome in Pediatric Obesity and Bariatric Surgery
by Cynthia Omoge Akagbosu, Evan Paul Nadler, Shira Levy and Suchitra Kaveri Hourigan
Int. J. Mol. Sci. 2022, 23(23), 15421; https://doi.org/10.3390/ijms232315421 - 06 Dec 2022
Cited by 2 | Viewed by 2735
Abstract
Obesity affects 42.4% of adults and 19.3% of children in the United States. Childhood obesity drives many comorbidities including hypertension, fatty liver disease, and type 2 diabetes mellitus. Prior research suggests that aberrant compositional development of the gut microbiome, with low-grade inflammation, precedes [...] Read more.
Obesity affects 42.4% of adults and 19.3% of children in the United States. Childhood obesity drives many comorbidities including hypertension, fatty liver disease, and type 2 diabetes mellitus. Prior research suggests that aberrant compositional development of the gut microbiome, with low-grade inflammation, precedes being overweight. Therefore, childhood may provide opportunities for interventions that shape the microbiome to mitigate obesity-related diseases. Children with obesity have gut microbiota compositional and functional differences, including increased proinflammatory bacterial taxa, compared to lean controls. Restoration of the gut microbiota to a healthy state may ameliorate conditions associated with obesity and help maintain a healthy weight. Pediatric bariatric (weight-loss) surgery is an effective treatment for childhood obesity; however, there is limited research into the role of the gut microbiome after weight-loss surgery in children. This review will discuss the magnitude of childhood obesity, the importance of the developing microbiome in establishing metabolic pathways, interventions such as bariatric surgery that may modulate the gut microbiome, and future directions for the potential development of microbiome-based therapeutics to treat obesity. Full article
(This article belongs to the Special Issue Gut Microbiota in Gastroenterology and Hepatology)
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16 pages, 314 KiB  
Review
A Concise Review of Liquid Chromatography-Mass Spectrometry-Based Quantification Methods for Short Chain Fatty Acids as Endogenous Biomarkers
by Neerja Trivedi, Helen E. Erickson, Veenu Bala, Yashpal S. Chhonker and Daryl J. Murry
Int. J. Mol. Sci. 2022, 23(21), 13486; https://doi.org/10.3390/ijms232113486 - 03 Nov 2022
Cited by 6 | Viewed by 2524
Abstract
Fatty acids are widespread naturally occurring compounds, and essential constituents for living organisms. Short chain fatty acids (SCFAs) appeared as physiologically relevant metabolites for their involvement with gut microbiota, immunology, obesity, and other pathophysiological functions. This has raised the demand for reliable analytical [...] Read more.
Fatty acids are widespread naturally occurring compounds, and essential constituents for living organisms. Short chain fatty acids (SCFAs) appeared as physiologically relevant metabolites for their involvement with gut microbiota, immunology, obesity, and other pathophysiological functions. This has raised the demand for reliable analytical detection methods in a variety of biological matrices. Here, we describe an updated overview of sample pretreatment techniques and liquid chromatography-mass spectrometry (LC-MS)-based methods for quantitative analysis of SCFAs in blood, plasma, serum, urine, feces and bacterial cultures. The present review incorporates various procedures and their applications to help researchers in choosing crucial parameters, such as pretreatment for complex biological matrices, and variables for chromatographic separation and detection, to establish a simple, sensitive, and robust quantitative method to advance our understanding of the role of SCFAs in human health and disease as potential biomarkers. Full article
(This article belongs to the Special Issue Gut Microbiota in Gastroenterology and Hepatology)
20 pages, 825 KiB  
Review
Influence of Foods and Nutrition on the Gut Microbiome and Implications for Intestinal Health
by Ping Zhang
Int. J. Mol. Sci. 2022, 23(17), 9588; https://doi.org/10.3390/ijms23179588 - 24 Aug 2022
Cited by 38 | Viewed by 11713
Abstract
Food components in our diet provide not only necessary nutrients to our body but also substrates for the mutualistic microbial flora in our gastrointestinal tract, termed the gut microbiome. Undigested food components are metabolized to a diverse array of metabolites. Thus, what we [...] Read more.
Food components in our diet provide not only necessary nutrients to our body but also substrates for the mutualistic microbial flora in our gastrointestinal tract, termed the gut microbiome. Undigested food components are metabolized to a diverse array of metabolites. Thus, what we eat shapes the structure, composition, and function of the gut microbiome, which interacts with the gut epithelium and mucosal immune system and maintains intestinal homeostasis in a healthy state. Alterations of the gut microbiome are implicated in many diseases, such as inflammatory bowel disease (IBD). There is growing interest in nutritional therapy to target the gut microbiome in IBD. Investigations into dietary effects on the composition changes in the gut microbiome flourished in recent years, but few focused on gut physiology. This review summarizes the current knowledge regarding the impacts of major food components and their metabolites on the gut and health consequences, specifically within the GI tract. Additionally, the influence of the diet on the gut microbiome-host immune system interaction in IBD is also discussed. Understanding the influence of the diet on the interaction of the gut microbiome and the host immune system will be useful in developing nutritional strategies to maintain gut health and restore a healthy microbiome in IBD. Full article
(This article belongs to the Special Issue Gut Microbiota in Gastroenterology and Hepatology)
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Other

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12 pages, 1878 KiB  
Brief Report
Ghrelin Alleviates Experimental Ulcerative Colitis in Old Mice and Modulates Colonocyte Metabolism via PPARγ Pathway
by Srilakshmi Muthyala, Robert S. Chapkin, Chaodong Wu and Chia-Shan Wu
Int. J. Mol. Sci. 2023, 24(1), 565; https://doi.org/10.3390/ijms24010565 - 29 Dec 2022
Cited by 1 | Viewed by 1728
Abstract
There is a growing prevalence of inflammatory bowel disease (IBD), a chronic inflammatory condition of the gastrointestinal tract, among the aging population. Ghrelin is a gut hormone that, in addition to controlling feeding and energy metabolism, has been shown to exert anti-inflammatory effects; [...] Read more.
There is a growing prevalence of inflammatory bowel disease (IBD), a chronic inflammatory condition of the gastrointestinal tract, among the aging population. Ghrelin is a gut hormone that, in addition to controlling feeding and energy metabolism, has been shown to exert anti-inflammatory effects; however, the effect of ghrelin in protecting against colitis in old mice has not been assessed. Here, we subjected old female C57BL/6J mice to dextran sulfate sodium (DSS) in drinking water for six days, then switched back to normal drinking water, administered acyl-ghrelin or vehicle control from day 3 to 13, and monitored disease activities throughout the disease course. Our results showed that treatment of old mice with acyl-ghrelin attenuated DSS-induced colitis. Compared to the DSS group, ghrelin treatment decreased levels of the inflammation marker S100A9 in the colons collected on day 14 but not on day 8, suggesting that the anti-inflammatory effect was more prominent in the recovery phase. Ghrelin treatment also significantly reduced F4/80 and interleukin-17A on day 14. Moreover, acyl-ghrelin increased mitochondrial respiration and activated transcriptional activity of the peroxisome proliferator-activated receptor gamma (PPARγ) in Caco-2 cells. Together, our data show that ghrelin alleviated DSS-induced colitis, suggesting that ghrelin may promote tissue repair in part through regulating epithelial metabolism via PPARγ mediated signaling. Full article
(This article belongs to the Special Issue Gut Microbiota in Gastroenterology and Hepatology)
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