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Beyond Digestion: The Role of Gut Microbiota in Metabolism, Immunity and Brain Function

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

Deadline for manuscript submissions: 20 July 2025 | Viewed by 3728

Special Issue Editor


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Guest Editor
Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA
Interests: intestinal epithelial physiology and pathophysiology; gut microbiome; inflammatory bowel disease; obesity; intestinal nutrient transport; gut infection; nutrition in health and disease
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Special Issue Information

Dear Colleagues,

In recent years, interest in gut microbiota–host crosstalk has significantly increased due to the enormous impact of gut microbiota on host health and diseases. Gut dysbiosis, which refers to changes in the composition, diversity, and metabolism of gut microbiota, can disrupt host–microbiota interactions and induce gut immune dysregulation. This dysregulation may be associated with the pathogenesis of several diseases, both within the gut and beyond, such as metabolic, cardiovascular, and neurological disorders. Dysbiosis may also contribute to the development and progression of mental health conditions such as anxiety, depression, and neurodevelopmental disorders. Indeed, a new paradigm, called the microbiota–gut–brain axis (MGBA), has emerged to explore the intricate and fascinating bidirectional connection between the gut (along with its microbiota) and the brain, in which the nervous and immune systems play indispensable roles. This Special Issue of IJMS welcomes manuscripts (mini reviews, research articles, and letters) that focus on the role of gut microbiota, microbial products (such as extracellular vesicles), and metabolites in modulating the health and disease conditions of the hosts, with a particular emphasis on intra- and interorgan communications. Research manuscripts featuring ample mechanistic studies, novel model systems, and studies that unravel the impact of novel microbial metabolites on host physiology will receive expedited consideration.

Dr. Alip Borthakur
Guest Editor

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Keywords

  • gut dysbiosis
  • gut microbiota
  • metabolism

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Published Papers (3 papers)

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Research

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14 pages, 1695 KiB  
Article
Gut Bacteria-Derived Tryptamine Ameliorates Diet-Induced Obesity and Insulin Resistance in Mice
by Jongjun Lee, Hye-Rim Jang, Dongjin Lee, Yeonmi Lee and Hui-Young Lee
Int. J. Mol. Sci. 2025, 26(3), 1327; https://doi.org/10.3390/ijms26031327 - 4 Feb 2025
Viewed by 1029
Abstract
Tryptophan is an essential amino acid that is metabolized in the intestine by gut bacteria into indole derivatives, including tryptamine. However, little is known about which bacterial tryptophan metabolites directly influence obesity. In this study, we identified tryptamine as a bacterial metabolite that [...] Read more.
Tryptophan is an essential amino acid that is metabolized in the intestine by gut bacteria into indole derivatives, including tryptamine. However, little is known about which bacterial tryptophan metabolites directly influence obesity. In this study, we identified tryptamine as a bacterial metabolite that significantly reduced fat mass following the intraperitoneal injection of five bacterial tryptophan end-products in a diet-induced obese mouse model. Interestingly, tryptamine, a serotonin analog, inhibited both lipogenesis and lipolysis in adipose tissue, which was further confirmed in a 3T3-L1 adipocyte cell culture study. Moreover, oral tryptamine supplementation markedly reduced fat mass and improved insulin sensitivity in a long-term, high-fat-diet, pair-feeding model. These studies demonstrate the therapeutic potential of tryptamine, a bacterial tryptophan metabolite, in ameliorating obesity and insulin resistance by directly regulating lipogenesis and lipolysis in white adipose tissue. Full article
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Review

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27 pages, 3457 KiB  
Review
Gut Microbiota Metabolites and Chronic Diseases: Interactions, Mechanisms, and Therapeutic Strategies
by Wenwen Liu, Lei Wang, Jinmei Ou, Daiyin Peng, Yue Zhang, Weidong Chen and Yanyan Wang
Int. J. Mol. Sci. 2025, 26(8), 3752; https://doi.org/10.3390/ijms26083752 - 16 Apr 2025
Viewed by 542
Abstract
The gut microbiota, shaped by factors such as diet, lifestyle, and genetics, plays a pivotal role in regulating host metabolism, immune function, and overall health. The diversity and balance of the gut microbiota are closely linked to the onset and progression of various [...] Read more.
The gut microbiota, shaped by factors such as diet, lifestyle, and genetics, plays a pivotal role in regulating host metabolism, immune function, and overall health. The diversity and balance of the gut microbiota are closely linked to the onset and progression of various chronic diseases. A growing body of evidence has demonstrated that alterations in the composition, function, and metabolites of the gut microbiota are significantly associated with cardiovascular diseases, including hypertension, atherosclerosis, and heart failure; metabolic disorders such as obesity, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease; and gastrointestinal conditions like inflammatory bowel disease and colorectal cancer. Despite substantial advances in microbiome research, challenges remain in fully elucidating the causal relationships between the gut microbiota and disease, as well as in translating these insights into clinical applications. This review aims to investigate the regulatory pathways via which the gut microbiota affects cardiovascular health, metabolic function, and gastrointestinal disease. Additionally, it highlights emerging strategies for the prevention and treatment of these chronic conditions, focusing on microbiota-targeted therapies and personalized dietary interventions as promising approaches for improving health outcomes. Full article
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17 pages, 287 KiB  
Review
Exploring Gut Microbiota-Targeted Therapies for Canine Idiopathic Epilepsy
by Luann Blanquet, Diana Serra, Carla Marrinhas and Anabela Almeida
Int. J. Mol. Sci. 2025, 26(4), 1742; https://doi.org/10.3390/ijms26041742 - 18 Feb 2025
Viewed by 1459
Abstract
Epilepsy stands out as one of the most prevalent chronic neurological conditions affecting companion animals. Recent research has increasingly focused on exploring the role of gut microbiota in influencing neurological conditions, like epilepsy. This influence stems from the bidirectional communication pathways between gut [...] Read more.
Epilepsy stands out as one of the most prevalent chronic neurological conditions affecting companion animals. Recent research has increasingly focused on exploring the role of gut microbiota in influencing neurological conditions, like epilepsy. This influence stems from the bidirectional communication pathways between gut bacteria and the brain, which involve metabolic, neural, immunological, and endocrine mechanisms. In fact, a balanced and stable gut microbiota is essential to maintaining normal gut physiology and ensuring appropriate signaling along the gut–brain axis. Conversely, dysbiosis can have detrimental effects on gut physiology and may contribute to the development or exacerbation of neurological conditions, including epilepsy. Considering these findings, this review article aims to deepen the understanding of the mechanisms underlying the microbiota–gut–brain connection in the context of canine idiopathic epilepsy. Moreover, this review presents recent data on innovative gut-related therapeutic strategies for canine idiopathic epilepsy treatment. Full article
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