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The Role of Diet and Medication in Shaping Gut Microbiota in Disease

A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Prebiotics, Probiotics and Postbiotics".

Deadline for manuscript submissions: 5 August 2026 | Viewed by 25665

Special Issue Editor

Dr. Hengameh Chloe Mirsepasi-Lauridsen

E-Mail Website
Guest Editor
Department of Clinical Microbiology, Copenhagen University Hospital Hvidovre, 2650 Hvidovre, Denmark
Interests: gastro-intestinal disease; dysbiosis; microbiology; diet; probiotic; prebiotic; fecal microbiota transplantation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The gut microbiota, consisting of trillions of microorganisms, plays a crucial role in maintaining human health. In the context of disease, its composition and function can be significantly influenced by external factors such as the environment and diet. It is essential to understand the interaction between gut microorganisms and diet and to develop strategies to maintain or restore a healthy gut microbiome. Furthermore, it is known that a fiber-rich diet is beneficial for healthy gut bacteria, producing short-chain fatty acids. In contrast, the Western diet, which is rich in high fats and sugar, can lead to an increase in harmful bacteria such as proteobacteria, which might contribute to metabolic disorders, including obesity and type 2 diabetes.

It is important to comprehend the effects of both diet on gut microbiota and personalize treatment approaches aimed at maintaining a healthy gut microbiome.

Dr. Hengameh Chloe Mirsepasi-Lauridsen
Guest Editor

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Keywords

  • gut microbiota
  • medication
  • antibiotics
  • diet
  • disease

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Published Papers (5 papers)

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Research

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14 pages, 3075 KB  
Article
Purified Diets Lacking Fermentable Fiber Reduce Microbial Diversity, Alter Epithelial Transcriptome, and Exacerbate Colitis
by Emma Griffith Thomas, Beulah Favour Ortutu, Jacob Connor Watson, Ethan Ong, Kaitlyn Eileen Blankley, Angela Meaurio Martin, Smriti Shankar, Dongmei Zhang, Devon Joseph Boland and Chia-Shan Wu
Nutrients 2026, 18(6), 891; https://doi.org/10.3390/nu18060891 - 11 Mar 2026
Viewed by 574
Abstract
Background/Objectives: Dietary fibers play key roles in shaping gut microbiome and intestinal homeostasis. While purified diets offer experimental precision and reproducibility in rodent models, they omit the complex mixture of fermentable and non-fermentable fibers found in grain-based chow diets. We hypothesized that [...] Read more.
Background/Objectives: Dietary fibers play key roles in shaping gut microbiome and intestinal homeostasis. While purified diets offer experimental precision and reproducibility in rodent models, they omit the complex mixture of fermentable and non-fermentable fibers found in grain-based chow diets. We hypothesized that excluding fermentable fiber impairs intestinal homeostasis by reducing microbial metabolites and altering the colonic epithelial transcriptome, thereby increasing susceptibility to inflammation. Methods: Wildtype male C57BL/6 mice were maintained on either a standard grain-based chow diet or a purified low-fat diet (LFD) containing 5% non-fermentable cellulose for ten weeks. Fecal microbiomes, short-chain fatty acid (SCFA) profiles, and colonic epithelial transcriptomes were analyzed. A separate group was challenged with dextran sodium sulfate (DSS) following a five-week dietary intervention to compare colitis severity between the two diet groups. Results: Relative to mice fed the grain-based chow, those consuming the purified LFD (containing only non-fermentable cellulose) showed decreased gut microbial diversity and significantly lower SCFA levels. These changes were accompanied by marked differences in colonic epithelial cell transcriptomes. In LFD-fed mice, the top upregulated gene networks included ribosomal pathways and MHC complex protein binding, suggesting increased growth and gut inflammation. The most downregulated pathways included mineral absorption, actin and tubulin binding, and membrane organelle assembly, indicating major alterations in cellular structure and transport. LFD-fed mice also exhibited increased colonic expression of S100a9, a gut inflammation biomarker, and more severe disease symptoms when challenged with DSS compared to chow-fed mice. Conclusions: Fermentable fibers are one of the factors contributing to intestinal homeostasis and mitigating the severity of ulcerative colitis. Full article
(This article belongs to the Special Issue The Role of Diet and Medication in Shaping Gut Microbiota in Disease)
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20 pages, 3010 KB  
Article
N-Acetylglucosamine and Immunoglobulin Strengthen Gut Barrier Integrity via Complementary Microbiome Modulation
by Emma De Beul, Jasmine Heyse, Michael Jurgelewicz, Aurélien Baudot, Lam Dai Vu and Pieter Van den Abbeele
Nutrients 2026, 18(2), 210; https://doi.org/10.3390/nu18020210 - 9 Jan 2026
Viewed by 1371
Abstract
Background: Gut barrier dysfunction and altered gut microbial metabolism are emerging signatures of chronic gut disorders. Considering growing interest in combining structurally and mechanistically distinct bioactives, we investigated the individual and combined effects of serum-derived bovine immunoglobulin (SBI) and N-acetylglucosamine (NAG) [...] Read more.
Background: Gut barrier dysfunction and altered gut microbial metabolism are emerging signatures of chronic gut disorders. Considering growing interest in combining structurally and mechanistically distinct bioactives, we investigated the individual and combined effects of serum-derived bovine immunoglobulin (SBI) and N-acetylglucosamine (NAG) on the gut microbiome and barrier integrity. Methods: The validated ex vivo SIFR® (Systemic Intestinal Fermentation Research) technology, using microbiota from healthy adults (n = 6), was combined with a co-culture of epithelial/immune (Caco-2/THP-1) cells. Results: While SBI and NAG already significantly improved gut barrier integrity (TEER, transepithelial electrical resistance, +21% and +29%, respectively), the strongest effect was observed for SBI_NAG (+36%). This potent combined effect related to the observation that SBI and NAG each induced distinct, complementary shifts in microbial composition and metabolite output. SBI most selectively increased propionate (~Bacteroidota families) and health-associated indole derivatives (e.g., indole-3-propionic acid), while NAG most specifically boosted acetate and butyrate (~Bifidobacteriaceae, Ruminococcaceae, and Lachnospiraceae). The combination of SBI_NAG displayed effects of the individual ingredients, thus, for instance, enhancing all three short-chain fatty acids (SCFA) and elevating microbial diversity (CMS, community modulation score). Conclusions: Overall, SBI and NAG exert complementary, metabolically balanced effects on the gut microbiota, supporting combined use, particularly in individuals with gut barrier impairment or dysbiosis linked to lifestyle or early-stage gastrointestinal disorders. Full article
(This article belongs to the Special Issue The Role of Diet and Medication in Shaping Gut Microbiota in Disease)
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Review

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22 pages, 630 KB  
Review
Gut Microbiota in IBD: The Beneficial and Adverse Effects of Diet and Medication
by Aidan Eric Juhl, Morten Westfall, Betina Hebbelstrup Jensen and Hengameh Chloé Mirsepasi-Lauridsen
Nutrients 2026, 18(1), 9; https://doi.org/10.3390/nu18010009 - 19 Dec 2025
Cited by 1 | Viewed by 1594
Abstract
Background: Inflammatory bowel disease (IBD) is a global disease with a considerable increase in prevalence and the impact on the health and well-being of patients suffering from this condition is vast. Diet has been suspected of being a contributor to IBD severity as [...] Read more.
Background: Inflammatory bowel disease (IBD) is a global disease with a considerable increase in prevalence and the impact on the health and well-being of patients suffering from this condition is vast. Diet has been suspected of being a contributor to IBD severity as well as intake of antibiotics. Methods: A literary search was conducted on the most recent studies on the subject of IBD, diet, and medical treatment to identify high-quality research findings within this area of research. Research published within the last decade was prioritized. Studies in English language were included in the search, and the knowledge gained was synthesized in the review. Results: Dietary patterns, specifically intake of Westernized diets, were associated with increased inflammation and increased disease severity in patients suffering from IBD, specifically patients suffering from Crohn’s disease (CD). A co-administration of pre- and probiotics was found to contribute to disease remission in ulcerative colitis patients, however, to a lesser extent in patients with CD. A bidirectional effect on the intestinal microbiome was seen as a result of intake of the medicines used for the treatment of IBD patients, which affects both bioavailability of the drug and efficacy of the treatment. The baseline composition of the intestinal microbiome in IBD patients dictates their response to the different treatments. Conclusions: Diet and medical treatment both have a large impact on the architecture of the intestinal Microbiome in IBD patients and are, as such, both essential to understand to enable individualized and optimized treatment. Full article
(This article belongs to the Special Issue The Role of Diet and Medication in Shaping Gut Microbiota in Disease)
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32 pages, 1846 KB  
Review
The Obesity–Epigenetics–Microbiome Axis: Strategies for Therapeutic Intervention
by Shabnam Nohesara, Hamid Mostafavi Abdolmaleky, Ahmad Pirani, Giuseppe Pettinato and Sam Thiagalingam
Nutrients 2025, 17(9), 1564; https://doi.org/10.3390/nu17091564 - 1 May 2025
Cited by 12 | Viewed by 4590
Abstract
Obesity (OB) has become a serious health issue owing to its ever-increasing prevalence over the past few decades due to its contribution to severe metabolic and inflammatory disorders such as cardiovascular disease, type 2 diabetes, and cancer. The unbalanced energy metabolism in OB [...] Read more.
Obesity (OB) has become a serious health issue owing to its ever-increasing prevalence over the past few decades due to its contribution to severe metabolic and inflammatory disorders such as cardiovascular disease, type 2 diabetes, and cancer. The unbalanced energy metabolism in OB is associated with substantial epigenetic changes mediated by the gut microbiome (GM) structure and composition alterations. Remarkably, experimental evidence also indicates that OB-induced epigenetic modifications in adipocytes can lead to cellular “memory” alterations, predisposing individuals to weight regain after caloric restriction and subsequently inducing inflammatory pathways in the liver. Various environmental factors, especially diet, play key roles in the progression or prevention of OB and OB-related disorders by modulating the GM structure and composition and affecting epigenetic mechanisms. Here, we will first focus on the key role of epigenetic aberrations in the development of OB. Then, we discuss the association between abnormal alterations in the composition of the microbiome and OB and the interplays between the microbiome and the epigenome in the development of OB. Finally, we review promising strategies, including prebiotics, probiotics, a methyl-rich diet, polyphenols, and herbal foods for the prevention and/or treatment of OB via modulating the GM and their metabolites influencing the epigenome. Full article
(This article belongs to the Special Issue The Role of Diet and Medication in Shaping Gut Microbiota in Disease)
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23 pages, 962 KB  
Review
Effects of GLP-1 Analogues and Agonists on the Gut Microbiota: A Systematic Review
by Krzysztof Ksawery Gofron, Andrzej Wasilewski and Sylwia Małgorzewicz
Nutrients 2025, 17(8), 1303; https://doi.org/10.3390/nu17081303 - 9 Apr 2025
Cited by 47 | Viewed by 16758
Abstract
Background: GLP-1 analogues are a relatively new class of medications that form the cornerstone of diabetes treatment. They possess invaluable glucose-lowering properties without hypoglycemic effects as well as strong cardioprotective effects. The gut microbiome has become the focus of numerous studies, demonstrating its [...] Read more.
Background: GLP-1 analogues are a relatively new class of medications that form the cornerstone of diabetes treatment. They possess invaluable glucose-lowering properties without hypoglycemic effects as well as strong cardioprotective effects. The gut microbiome has become the focus of numerous studies, demonstrating its influence not only on the gut but also on the overall well-being of the entire body. However, the effects of GLP-1 analogs on gut microbiota remain uncertain. Scope of review: Our systematic review (based on PRISMA guidelines) aimed to gather knowledge on the effects of GLP-1 analogue medications on the composition, richness, and abundance of gut microbiota in both animal and human models. Conclusions: Thirty-eight studies were included in this systematic review. GLP-1 analogues have demonstrated a notable impact on the composition, richness, and diversity of gut microbiota. We can conclude, following the obtained research results of our study, that liraglutide promotes the growth of beneficial genera relevant for beneficial metabolic functions. Exenatide and exendin-4 administration showed various effects on the microbiome composition in animal and human studies. In animal models, it increased genera associated with improved metabolism; however, in human models, genera linked to better metabolic functions and escalated inflammation increased. Following dulaglutide administration, increases in Bacteroides, Akkermansia, and Ruminococcus, genera connected to an improved metabolic model, were significant. Finally, varied results were obtained after semaglutide treatment, in which A. muciniphila, known for its positive metabolic functions, increased; however, microbial diversity decreased. Semaglutide treatment provided various results indicating many confounding factors in semaglutide’s impact on the gut microbiota. Results varied due to dissimilarities in the studied populations and the duration of the studies. Further research is essential to confirm these findings and to better recognize their implications for the clinical outcomes of patients. Full article
(This article belongs to the Special Issue The Role of Diet and Medication in Shaping Gut Microbiota in Disease)
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