Gut Microbiome and Metabolome Studies in Animal Models: Clinical, Translational, and Basic Research Applications

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Animal Metabolism".

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 9879

Special Issue Editors


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Guest Editor
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA
Interests: veterinary clinical medicine; nutrition and metabolism; gut microbiome; metabolomics; probiotics; prebiotics; synbiotics; antibiotic resistance; translational medicine

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Guest Editor
Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA
Interests: fecal microbiota transplantation; veterinary clinical pathology; gut microbiome; multiomics; metabolomics; infectious disease; One Health

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Guest Editor
Section Editor, Department of Food Science and Nutrition, University of Minnesota, St. Paul, MN 55108, USA
Interests: animal nutrition; metabolomics; microbial metabolism; nutrient metabolism; nutritional biochemistry; xenobiotic metabolism
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Special Issue Information

Dear Colleagues,

Animals are critical to the health and wellbeing of people across the globe through their roles as companions, agricultural commodities, or in translational models for biomedical research.

Metabolomics, the systematic investigation of small molecules in living systems, is continually developing our understanding of animal health and disease. The impact of metabolomics has been expanded in part due to advancements in microbiome sciences.

The interconnectivity of metabolomics and the microbiome is especially notable in gut microbial ecosystems. Here, integrated microbiome and metabolome analyses have elucidated the functional mechanisms by which the gut microbiome interacts with a host. Using animal models, these analyses have increased our awareness of how environmental factors, including diet, drugs, and biologic agents (e.g., probiotics, prebiotics, synbiotics, bacteriophages), modulate gut microbiome function.  Collectively, the findings of these studies have been applied to improve clinical outcomes for people and animals, and they illustrate the increasing need for further investigation into gut microbiome and host interactions.

This Special Issue welcomes the submission of novel research papers with an emphasis on gut microbiome and metabolome studies in animal models. Topics that will be covered include (but are not limited to) basic, pre-clinical, and clinical research studies using animal models in the following aims:

I. To understand the role(s) of the gut microbiome and metabolome in the prevention and treatment of infectious and/or chronic diseases.
ii. To assess the utility and feasibility of gut microbiome and metabolome endpoints, including biomarkers, in clinical veterinary diagnostics.iii. To evaluate novel therapeutics in animals that work via modulation of the gut microbiome and metabolome, including biologic therapeutics (e.g., probiotics, prebiotics, synbiotics, bacteriophages, etc.).

Neither in vitro nor ex vivo models will be considered in this Special Issue. Additionally, studies that only present metabolomic data without concurrent microbiome analysis will not be considered.

Dr. Nora Jean Nealon
Dr. Nina Kristen E. Randolph
Dr. Chi Chen
Guest Editors

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Keywords

  • gut microbiome
  • metabolome
  • animal model
  • microbial metabolism
  • host–microbe interactions
  • veterinary medicine
  • gut metagenomics
  • gut metabolomics

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Published Papers (4 papers)

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17 pages, 4454 KiB  
Article
Longitudinal Characterization of the Gut Microbiota in the Diabetic ZDSD Rat Model and Therapeutic Potential of Oligofructose
by Savanna N. Weninger, Angela Ding, Elizabeth N. Browne, Morgan L. Frost, Gabriele Schiro, Daniel Laubitz and Frank A. Duca
Metabolites 2023, 13(5), 660; https://doi.org/10.3390/metabo13050660 - 16 May 2023
Cited by 5 | Viewed by 1803
Abstract
The complex development of type 2 diabetes (T2D) creates challenges for studying the progression and treatment of the disease in animal models. A newly developed rat model of diabetes, the Zucker Diabetic Sprague Dawley (ZDSD) rat, closely parallels the progression of T2D in [...] Read more.
The complex development of type 2 diabetes (T2D) creates challenges for studying the progression and treatment of the disease in animal models. A newly developed rat model of diabetes, the Zucker Diabetic Sprague Dawley (ZDSD) rat, closely parallels the progression of T2D in humans. Here, we examine the progression of T2D and associated changes in the gut microbiota in male ZDSD rats and test whether the model can be used to examine the efficacy of potential therapeutics such as prebiotics, specifically oligofructose, that target the gut microbiota. Bodyweight, adiposity, and fed/fasting blood glucose and insulin were recorded over the course of the study. Glucose and insulin tolerance tests were performed, and feces collected at 8, 16, and 24 weeks of age for short-chain fatty acids and microbiota analysis using 16s rRNA gene sequencing. At the end of 24 weeks of age, half of the rats were supplemented with 10% oligofructose and tests were repeated. We observed a transition from healthy/nondiabetic to prediabetic and overtly diabetic states, via worsened insulin and glucose tolerance and significant increases in fed/fasted glucose, followed by a significant decrease in circulating insulin. Acetate and propionate levels were significantly increased in the overt diabetic state compared to healthy and prediabetic. Microbiota analysis demonstrated alterations in the gut microbiota with shifts in alpha and beta diversity as well as alterations in specific bacterial genera in healthy compared to prediabetic and diabetic states. Oligofructose treatment improved glucose tolerance and shifted the cecal microbiota of the ZDSD rats during late-stage diabetes. These findings underscore the translational potential of ZDSD rats as a model of T2D and highlight potential gut bacteria that could impact the development of the disease or serve as a biomarker for T2D. Additionally, oligofructose treatment was able to moderately improve glucose homeostasis. Full article
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15 pages, 22835 KiB  
Article
Integrated Serum Metabolome and Gut Microbiome to Decipher Chicken Amino Acid Improvements Induced by Medium-Chain Monoglycerides
by Tao Liu, Shengyue Ruan, Qiufen Mo, Minjie Zhao, Jing Wang, Zhangying Ye, Li Chen and Fengqin Feng
Metabolites 2023, 13(2), 208; https://doi.org/10.3390/metabo13020208 - 30 Jan 2023
Cited by 5 | Viewed by 2197
Abstract
Chicken muscle yield and amino acid composition improvements with medium-chain monoglyceride (MG) supplementation were reported by previous studies, but the underlying mechanism was uncertain. This study aimed to decipher chicken amino acid improvements induced by medium-chain monoglycerides in the views of metabolomics, gene [...] Read more.
Chicken muscle yield and amino acid composition improvements with medium-chain monoglyceride (MG) supplementation were reported by previous studies, but the underlying mechanism was uncertain. This study aimed to decipher chicken amino acid improvements induced by medium-chain monoglycerides in the views of metabolomics, gene expression, and the gut microbiome. Newly hatched chicks (12,000 chicks) were weighed and randomly divided into two flocks, each with six replicates (1000 chicks per replicate), and fed a basal diet (the control group, CON) or a basal diet enriched with 300 mg/kg MG (the treated group, MG). Results demonstrated that MGs significantly increased the chicken flavor and essential and total amino acids. The serum amino acids and derivatives (betaine, l-leucine, l-glutamine, 1-methylhistide), as well as amino acid metabolism pathways in chickens, were enhanced by MG supplementation. Gene expression analysis exhibited that dietary MGs could improve muscle protein synthesis and cell growth via the mTOR/S6K1 pathway. Dietary MGs enhanced the cecal amino acid metabolism by selectively increasing the proportion of genera Lachnospiraceae_NK4A136_group and Bacteroides. Conclusively, the present study demonstrated that dietary MGs improved chicken amino acid composition via increasing both gut amino acid utilization and muscle amino acid deposition. Full article
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14 pages, 2539 KiB  
Article
Early Life Polychlorinated Biphenyl 126 Exposure Disrupts Gut Microbiota and Metabolic Homeostasis in Mice Fed with High-Fat Diet in Adulthood
by Yuan Tian, Bipin Rimal, Wei Gui, Imhoi Koo, Philip B. Smith, Shigetoshi Yokoyama and Andrew D. Patterson
Metabolites 2022, 12(10), 894; https://doi.org/10.3390/metabo12100894 - 23 Sep 2022
Cited by 6 | Viewed by 3071
Abstract
Evidence supports the potential influence of persistent organic pollutants (POPs) on the pathogenesis and progression of obesity and diabetes. Diet-toxicant interactions appear to be important in diet-induced obesity/diabetes; however, the factors influencing this interaction, especially the early life environmental exposure, are unclear. Herein, [...] Read more.
Evidence supports the potential influence of persistent organic pollutants (POPs) on the pathogenesis and progression of obesity and diabetes. Diet-toxicant interactions appear to be important in diet-induced obesity/diabetes; however, the factors influencing this interaction, especially the early life environmental exposure, are unclear. Herein, we investigated the metabolic effects following early life five-day exposure (24 μg/kg body weight per day) to 3,3′,4,4′,5-pentacholorobiphenyl (PCB 126) at four months after exposure in mice fed with control (CTRL) or high-fat diet (HFD). Activation of aryl hydrocarbon receptor (AHR) signaling as well as higher levels of liver nucleotides were observed at 4 months after PCB 126 exposure in mice, independent of diet status. Inflammatory responses including higher levels of serum cytokines and adipose inflammatory gene expression caused by early life PCB 126 were observed only in HFD-fed mice in adulthood. Notably, early life PCB 126 exposure worsened HFD-induced impaired glucose homeostasis characterized by glucose intolerance and elevated gluconeogenesis and tricarboxylic acid (TCA) cycle flux without worsening the effects of HFD related to adiposity in adulthood. Furthermore, early life PCB 126 exposure resulted in diet-dependent changes in bacterial community structure and function later in life, as indicated by metagenomic and metabolomic analyses. These data contribute to a more comprehensive understanding of the interactions between diet and early life environmental chemical exposure. Full article
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18 pages, 3121 KiB  
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Effect of Aerobic Exercise on Intestinal Microbiota with Amino Acids and Short-Chain Fatty Acids in Methamphetamine-Induced Mice
by Xin Liang, Xue Li, Yu Jin, Yi Wang, Changling Wei and Zhicheng Zhu
Metabolites 2023, 13(3), 361; https://doi.org/10.3390/metabo13030361 - 28 Feb 2023
Cited by 5 | Viewed by 2150
Abstract
This study aimed to investigate the changes in intestinal homeostasis and metabolism in mice after methamphetamine (MA) administration and exercise intervention. In this study, male C57BL/B6J mice were selected to establish a model of methamphetamine-induced addiction, and the gut microbiota composition, short-chain fatty [...] Read more.
This study aimed to investigate the changes in intestinal homeostasis and metabolism in mice after methamphetamine (MA) administration and exercise intervention. In this study, male C57BL/B6J mice were selected to establish a model of methamphetamine-induced addiction, and the gut microbiota composition, short-chain fatty acids (SCFAs), and amino acid levels were assessed by 16S rRNA, liquid chromatography–tandem mass spectrometry, and gas chromatography–tandem mass spectrometry, respectively. The results showed that 23 dominant microbiota, 12 amino acids, and 1 SCFA were remarkably higher and 9 amino acids and 6 SCFAs were remarkably lower in the exercise model group than in the control group. Among the top 10 markers with opposite trends between the exercise intervention group and model group, the differential microbiomes included Oscillibacter, Alloprevotella, Colidextribacter, Faecalibaculum, Uncultured, Muribaculaceae, and Negativibacillus; amino acids included proline; and SCFAs included isovaleric acid and pentanoic acid. Proline was negatively correlated with Negativibacillus and positively correlated with pentanoic acid. The results suggested that moderate-intensity aerobic exercise may modulate changes in the composition of the gut microbiota and the levels of amino acids and SCFAs induced by MA administration. Full article
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