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The Gut Microbiota at the Crossroads of Chronic Disease: Biological Functions, Disruptions, and Innovations in Therapy

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

Deadline for manuscript submissions: 20 December 2026 | Viewed by 5402

Editors

Dr. Joanna Fotschki

E-Mail Website
Guest Editor
Division of Food Science, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Tuwima 10, 10-748 Olsztyn, Poland
Interests: microbiota; microbiome; immune system; intestine; bioactive compounds; food; nutrition; inflammation; food allergy
Special Issues, Collections and Topics in MDPI journals
Dr. Bartosz Fotschki

E-Mail Website
Guest Editor
Division of Food Science, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Tuwima 10, 10-748 Olsztyn, Poland
Interests: in vivo experiments; nutrition; oxidative stress; inflammation; obesity; liver disorders; gut-microbiota-derived metabolites; metabolic disorders; interaction between the gut and liver
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Growing evidence shows that the gut microbiota and the bioactive metabolites it produces are central to human physiology. Disturbances in microbial composition and function are increasingly recognized as contributors to the development and progression of chronic conditions, including metabolic syndrome, autoimmune disorders, neurodegenerative diseases, and mood-related pathologies. These imbalances arise from a combination of genetic predispositions, dietary patterns, environmental exposures, and ageing.

The past decade has seen remarkable advances in microbiome science, revealing how microbial communities regulate host immunity, inflammation, nutrient metabolism, and gut barrier integrity. Disruptions in these processes can initiate systemic effects, influencing distant organs through mechanisms such as the gut–brain axis, gut–liver crosstalk, and immune modulation. Understanding these pathways opens the door to novel dietary, microbiota-targeted, and personalized interventions for chronic disease prevention and management.

This Special Issue welcomes contributions that deepen our understanding of how dietary and nutritional factors affect the gut microbiota and the onset and progression of chronic diseases. We encourage submissions that explore microbial metabolites, host–microbe interactions, microbiome-modulating strategies, and translational approaches with clinical or nutritional relevance. Both original research articles and comprehensive reviews are invited.

We look forward to your contributions to advancing this dynamic field.

Dr. Joanna Fotschki
Dr. Bartosz Fotschki
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Nutrients is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • gut microbiota
  • dysbiosis
  • intestinal bacteria
  • chronic diseases
  • gut–brain axis
  • probiotics
  • prebiotics
  • psychobiotics
  • metabolic disorders
  • autoimmune disorders
  • immune response
  • dietary interventions

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Published Papers (4 papers)

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Research

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16 pages, 507 KB  
Article
Nordic Walking Combined with Time-Restricted Eating Is Associated with Changes in Gut Microbiota Composition in Adults with Obesity—Pilot Study
by Alicja Nowak-Zaleska, Olga Czerwińska-Ledwig, Małgorzata Żychowska, Katarzyna Meyza, Dorota Łoboda, Tomasz Pałka, Agata Szlachetka, Ewa Ziemann, Tomasz Niewęgłowski and Anna Kurkiewicz-Piotrowska
Nutrients 2026, 18(14), 2373; https://doi.org/10.3390/nu18142373 - 20 Jul 2026
Viewed by 358
Abstract
Background/Objectives: Rearrangement of the gut microbiota toward a symbiotic profile may be influenced by physical activity and diet in both healthy and obese individuals. This study aimed to characterize gut microbiota using next-generation sequencing (NGS) and to evaluate the effect of a 6-week [...] Read more.
Background/Objectives: Rearrangement of the gut microbiota toward a symbiotic profile may be influenced by physical activity and diet in both healthy and obese individuals. This study aimed to characterize gut microbiota using next-generation sequencing (NGS) and to evaluate the effect of a 6-week Nordic Walking (NW) program combined with Time-Restricted Eating (TRE; 10 h eating window) in individuals with obesity. Methods: The study included healthy controls (C; n = 10; 64.7 ± 6.7 years) and individuals with obesity (A; n = 10; 60.0 ± 4.5 years). The intervention consisted of three moderate-intensity NW sessions per week, individually adapted to participants’ capacity. Gut microbiota was analyzed using nanopore 16S rRNA sequencing (V3–V9 regions). Results: Baseline microbial composition differed significantly between obese and control groups, with Bray–Curtis dissimilarity ranging from 49.98% (phylum) to 65.97% (species) (p ≤ 0.02). After intervention, within-group dissimilarity in the obese cohort (A vs. B) decreased to 25.24–51.86% but was not significant (p = 0.88–1.00). Post-intervention comparisons (B vs. C) still showed significant differences at higher taxonomic levels, including class (44.10%, p = 0.015), order (31.62%, p = 0.022), family (50.48%, p = 0.011), genus (58.09%, p = 0.005), and species (63.47%, p = 0.0003). Alpha diversity showed no significant differences at species and genus levels, but significant group effects were observed at higher ranks, including order (Shannon p = 0.01; Simpson p = 0.01), class (Simpson p = 0.02), and phylum (Shannon p = 0.02). Conclusions: The NW + TRE intervention was associated with partial normalization of gut microbiota structure and reduced microbial dissimilarity, suggesting a shift toward a more symbiotic profile; however, differences compared with controls persisted, indicating incomplete convergence after 6 weeks. Full article
(This article belongs to the Special Issue The Gut Microbiota at the Crossroads of Chronic Disease: Biological Functions, Disruptions, and Innovations in Therapy)
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23 pages, 3298 KB  
Article
Dietary Fibre Modulates Gut Microbiota Responses to Copper Nanoparticles
by Bartosz Fotschki, Dorota Napiórkowska, Joanna Fotschki, Kamil Myszczyński, Ewelina Cholewińska, Katarzyna Ognik and Jerzy Juśkiewicz
Nutrients 2026, 18(5), 828; https://doi.org/10.3390/nu18050828 - 3 Mar 2026
Cited by 1 | Viewed by 919
Abstract
Background/Objectives: Although copper nanoparticles (Cu-NPs) are increasingly explored as food and feed additives, there is still limited evidence on how the commonly consumed dietary fibre matrix modulates their effects on the gut microbiota. This study evaluated whether different dietary fibres (cellulose, pectin, inulin, [...] Read more.
Background/Objectives: Although copper nanoparticles (Cu-NPs) are increasingly explored as food and feed additives, there is still limited evidence on how the commonly consumed dietary fibre matrix modulates their effects on the gut microbiota. This study evaluated whether different dietary fibres (cellulose, pectin, inulin, psyllium) modulate Cu-NP–driven changes in caecal microbiota activity, composition, and bile acid metabolism in rats in a multifactorial design accounting for fibre type, copper dose, and copper form. Methods: Wistar male rats (n = 10 per group, 10 groups) were fed semi-purified diets for 6 weeks. Cu-NPs were provided at 6.5 or 13 mg Cu/kg diet and combined with cellulose (control fibre) or with pectin, inulin, or psyllium. Caecal digesta parameters, microbial enzyme activities, short-chain fatty acids (SCFAs), bile acids, and 16S rRNA sequencing were used to assess microbial diversity. Results: Final body weight did not differ among groups, whereas feed intake decreased most consistently with inulin and psyllium. Inulin and psyllium increased caecal digesta and tissue mass, while pectin increased caecal ammonia. Higher Cu-NPs dose reduced several microbial enzyme activities and lowered major SCFAs across most treatments; pectin most strongly preserved/enhanced glycosidase activities and was associated with increased SCFA levels vs. control, with a 32% rise in acetate, a 47% rise in propionate, and a 61% rise in butyrate. Fibre type dominated bile acid outcomes: psyllium reduced total bile acids by 11.8% vs. control, while inulin increased muricholic acids by 216% vs. control. Microbiota alpha and beta diversity separated primarily by fibre type, with distinct clustering particularly in pectin-fed groups. Across comparisons, Mucispirillum was consistently reduced in fibre-supplemented groups vs. cellulose, alongside recurrent changes in selected genera; functional profiling highlighted shared shifts in carbohydrate, fermentation, transport, and stress-response features under Cu-NPs exposure. Conclusions: The gastrointestinal and microbiota responses to Cu-NPs are strongly fibre-dependent; thus, Cu-NP safety and functionality should be evaluated together with the accompanying dietary fibre matrix, not as a standalone exposure. Implications for humans remain indirect and require confirmation in human-relevant models and clinical settings. Full article
(This article belongs to the Special Issue The Gut Microbiota at the Crossroads of Chronic Disease: Biological Functions, Disruptions, and Innovations in Therapy)
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Review

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31 pages, 2256 KB  
Review
The Gut Microbiota as a Mediator Linking the MIND Diet to Alzheimer’s Disease
by Fatemeh Ramezani, Sina S. Herfeh and Emily Burke
Nutrients 2026, 18(9), 1445; https://doi.org/10.3390/nu18091445 - 30 Apr 2026
Viewed by 1397
Abstract
The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet has emerged as a promising dietary pattern associated with reduced Alzheimer’s disease (AD) risk, supported by growing evidence that both diet and the gut microbiota are modifiable contributors to disease development and progression. Observational studies [...] Read more.
The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet has emerged as a promising dietary pattern associated with reduced Alzheimer’s disease (AD) risk, supported by growing evidence that both diet and the gut microbiota are modifiable contributors to disease development and progression. Observational studies have linked higher MIND diet adherence to lower AD incidence and slower cognitive decline, with certain comparative analyses reporting stronger associations with cognitive outcomes than those observed for the parent Mediterranean or DASH diets. Developed specifically to support cognitive health, the MIND diet emphasizes leafy green vegetables, berries, and olive oil while restricting butter, cheese, fried foods, sweets, and red meat. While these features suggest a biologically plausible basis for neuroprotection, the underlying mechanisms remain incompletely defined. The microbiota–gut–brain axis offers a potential mechanistic framework, as diet is a major determinant of gut microbiota composition and microbiota-derived metabolites that may influence brain function and AD-related pathways. However, direct evidence characterizing MIND diet-specific effects on the gut microbiota remains limited, with most mechanistic insights derived from related dietary patterns or individual dietary components. Accordingly, this review synthesizes evidence from these related dietary patterns and key MIND components to propose a conceptual framework linking the MIND diet, the gut microbiota, and AD risk, while highlighting priorities for future research. Full article
(This article belongs to the Special Issue The Gut Microbiota at the Crossroads of Chronic Disease: Biological Functions, Disruptions, and Innovations in Therapy)
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43 pages, 2170 KB  
Review
The Gut Gambit: A Review of How Microbial Imbalance Fuels Metabolic Mayhem
by Lakshmayya Nunna Sai Venkata, Awdhesh Kumar Mishra, Yugal Kishore Mohanta, Sarvesh Rustagi, Ashutosh Bahuguna, Anjali Tomar, Kwang-Hyun Baek and Bishwambhar Mishra
Nutrients 2026, 18(6), 888; https://doi.org/10.3390/nu18060888 - 11 Mar 2026
Cited by 2 | Viewed by 2164
Abstract
Background/Objectives: An imbalance in gut microbiota, known as gut dysbiosis, results in reactive oxygen species overproduction, which can cause inflammatory conditions, damage DNA, trigger immunity, and induce epigenetic modifications of crucial genes that regulate metabolic pathways. Such a condition can also weaken the [...] Read more.
Background/Objectives: An imbalance in gut microbiota, known as gut dysbiosis, results in reactive oxygen species overproduction, which can cause inflammatory conditions, damage DNA, trigger immunity, and induce epigenetic modifications of crucial genes that regulate metabolic pathways. Such a condition can also weaken the resilience of the protective gut wall and elevate colon permeability, allowing toxins from the gut to reach the liver and bloodstream, contributing to oxidative damage, autoimmune diseases, and epigenetic changes linked to metabolic disorders. Methods: The Scopus database was exclusively searched for the literature. Relevant articles were identified using predefined keywords, including gut dysbiosis, microbiota, microbiome, oxidative stress, metabolic disorders, inflammation, and epigenetics or combinations. Gut microbiota- and diet-induced metabolic disorders, particularly obesity, insulin resistance, dyslipidemia, and hypertension, may be inherited through epigenetic pathways. Results: The evidence analyzed suggests that the gut microbiota serves as a diverse metabolic and immunological organ. Its disruption affects the production of short-chain fatty acids, bile acid metabolism, immune signaling, and the redox balance, which contributes to the development of obesity, insulin resistance, and metabolic syndrome. Conclusions: This review highlights key epigenetic mechanisms underlying metabolic disorders and oxidative stress in the context of gut dysbiosis. Furthermore, therapeutic strategies targeting the gut microbiota, such as dietary interventions, prebiotics, probiotics, postbiotics, and fecal microbiota transplantation, hold promise for mitigating oxidative stress and inflammation associated with metabolic syndrome. Full article
(This article belongs to the Special Issue The Gut Microbiota at the Crossroads of Chronic Disease: Biological Functions, Disruptions, and Innovations in Therapy)
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