nutrients-logo

Journal Browser

Journal Browser

Disease-Associated Gut Microbiota Patterns, Nutritional Factors, and Host Immunity

A Special Issue of Nutrients (ISSN 2072-6643) belonging to the section "Nutritional Immunology".

Deadline for manuscript submissions: 25 October 2026 | Viewed by 5225

Editor


E-Mail Website
Guest Editor
Department of Infectology, Faculty of Medicine, University of Debrecen, Bartok Bela Street 2-26, 4031 Debrecen, Hungary
Interests: immunopathogenesis; gut microbiota; host immunity; celiac disease; inflammatory bowel disease; inflammatory bowel disease; diet; nutritional interventions; immune responses

Special Issue Information

Dear Colleagues,

The gut microbiota play a central role in shaping host immune homeostasis and systemic inflammatory responses. Increasing evidence suggests that the distinct disease-associated patterns of gut microbiota are linked to varied human disorders, including autoimmune, inflammatory, metabolic, and neurological diseases. At the same time, dietary and nutritional factors are among the most important modulators of gut microbial composition and function.

This Special Issue will explore how nutritional factors influence disease-associated gut microbiota patterns and how these interactions affect host immune responses. Particular attention will be paid to studies investigating diet–microbiota–immune interactions, the role of dietary components and microbial metabolites in immune regulation, and the impact of nutrition-driven microbiota alterations on disease pathogenesis.

Topics of interest include dietary modulation of gut microbiota, microbiota-derived metabolites, gut barrier function, immune dysregulation associated with microbial alterations, and microbiota-targeted nutritional strategies such as probiotics, prebiotics, and dietary interventions.

Both original research articles and high-quality reviews addressing mechanistic, translational, and clinical aspects of nutrition–microbiota–immune interactions in human disease are welcome.

Dr. Zsolt Barta
Guest Editor

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
  • host immunity
  • nutrition
  • diet
  • diet–microbiota interactions
  • microbial dysbiosis
  • celiac disease
  • inflammatory bowel disease
  • autoimmune diseases
  • microbial metabolites
  • gut barrier
  • probiotics
  • prebiotics
  • postbiotics

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • Reprint: MDPI Books provides the opportunity to republish successful Special Issues in book format, both online and in print.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (6 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

15 pages, 11663 KB  
Article
Oral Sodium Butyrate Is Associated with Altered Tissue Bacterial Antigens and Innate Immune Marker Expression Across Different Organs in Athymic Mice
by Abubakr H. Mossa, Walaa Sherif Mohammed Alhalabi, Sylia Chehade, Razaz Omer Osman Alnakhli, Ibrahim Yaseen Hachim and Mahmood Y. Hachim
Nutrients 2026, 18(16), 2604; https://doi.org/10.3390/nu18162604 - 10 Aug 2026
Viewed by 408
Abstract
Background: Butyrate is a microbiota-derived short-chain fatty acid with established roles in maintaining intestinal barrier integrity and regulating immune responses. Although its effects have been extensively investigated in immunocompetent models, systemic immune homeostasis in severely immunodeficient hosts remains incompletely understood. This exploratory study [...] Read more.
Background: Butyrate is a microbiota-derived short-chain fatty acid with established roles in maintaining intestinal barrier integrity and regulating immune responses. Although its effects have been extensively investigated in immunocompetent models, systemic immune homeostasis in severely immunodeficient hosts remains incompletely understood. This exploratory study evaluated the impact of sodium butyrate (NaB) supplementation on tissue-associated microbial antigen detection and immune marker distribution along different organs in athymic nude mice. Methods: Female NU/J athymic mice were administered either regular drinking water (H2O, n = 10) or NaB-supplemented water (150 mM, n = 5) for six weeks. Intestinal, liver, lung, and kidney tissues were collected for histopathological and immunohistochemical analyses. Expression of microbial antigens, including lipopolysaccharide (LPS) and lipoteichoic acid (LTA), as well as immune-associated markers (CD3, CD8a, CD68, CD278, and transglutaminase-2 [TGM2]), was assessed using a semiquantitative scoring system. Results: NaB supplementation did not significantly affect organ morphology but was associated with better weight gain. Histological examination revealed preserved tissue architecture in all organs, with only mild condensation of small intestinal crypts in NaB-treated mice. Immunohistochemical analysis showed consistently lower LPS expression in NaB-treated animals compared with controls in the small intestine, liver, and kidney, with a borderline reduction in the lungs. Reduced LPS detection was accompanied by significantly lower expression of the macrophage marker CD68 in the kidney. Conclusions: Oral NaB supplementation was associated with lower detection of bacterial antigens in tissues and reduced innate immune expression across multiple organs. These findings support a potential role for butyrate in limiting microbial expression and systemic inflammatory signaling in athymic mice. Full article
Show Figures

Figure 1

20 pages, 3840 KB  
Article
Fatigue-Associated Alterations in Gut Microbiota, Mitochondrial Energy Metabolism, and Immune Function in Mice: Implications for Future Nutrition Studies
by Menghui She, Huiyi Peng, Qin Liu and Zhoujin Tan
Nutrients 2026, 18(12), 2031; https://doi.org/10.3390/nu18122031 - 22 Jun 2026
Cited by 1 | Viewed by 636
Abstract
Background: This study investigated the relationships among mitochondrial energy metabolism, immune function, and gut microbiota in mice under a fatigued state, providing preliminary evidence for future nutrition-related mechanistic and intervention studies. Methods: Mice were adaptively fed for 4 days and then randomly divided [...] Read more.
Background: This study investigated the relationships among mitochondrial energy metabolism, immune function, and gut microbiota in mice under a fatigued state, providing preliminary evidence for future nutrition-related mechanistic and intervention studies. Methods: Mice were adaptively fed for 4 days and then randomly divided into a normal control group (NC) and a fatigue model group (NM). Immune organ indices, serum IgG levels, thigh muscle ATP content, mitochondrial respiratory chain complex I–IV activities, and gut microbiota composition were assessed using enzyme-linked immunosorbent assay (ELISA), microplate assays, and 16S rRNA gene sequencing. Results: Compared with the NC, the NM showed a significantly reduced spleen index, serum IgG levels, mitochondrial respiratory chain complex I, III, and IV activities, along with reduced ATP content. Regarding gut microbiota, mice in the NM exhibited disordered intestinal villus arrangement, inflammatory cell infiltration in the crypts and muscular layers, and markedly reduced intestinal microbial activity as well as protease and sucrase activities. 16S rRNA sequencing revealed fewer ASVs in the NM, with enrichment of Lactobacillaceae, Limosilactobacillus, and Ligilactobacillus, whereas the NC was characterized by Borkfalkiaceae and Borkfalkia. Linear discriminant analysis effect size (LEfSe) analysis identified Lactobacillaceae, Firmicutes_D, and Lactobacillales as characteristic taxa of the NM. Kyoto Encyclopedia of Genes and Genomes (KEGG) prediction indicated that fatigue-associated microbial functions were mainly related to carbohydrate, amino acid, and lipid metabolism. Correlation and RDA analyses further suggested that alterations in gut microbiota structure were closely associated with mitochondrial energy-related indicators and immune-related parameters. Conclusions: Fatigue was associated with alterations in energy metabolism, immune function, and gut microecology in mice. The “gut microbiota–energy metabolism–immunity” framework may represent a potential association-based framework and provides biological information to support future nutrition-related intervention studies. Full article
Show Figures

Figure 1

21 pages, 38225 KB  
Article
New Insights into Diarrhea Caused by High-Fat Diet and Fatigue: Gut Microbiota Dysbiosis-Driven Bile Acid Metabolism Disorder
by Qin Liu, Huiyi Peng, Xuejiao Xie, Miao Jiang, Maijiao Peng and Zhoujin Tan
Nutrients 2026, 18(9), 1317; https://doi.org/10.3390/nu18091317 - 22 Apr 2026
Cited by 4 | Viewed by 1138
Abstract
Background: This study investigated the mechanisms underlying diarrhea induced by a high-fat diet (HFD) under a state of fatigue, focusing on gut microbiota dysbiosis, bile acid metabolic disturbance, and gut–liver injury. Methods: Mice were assigned to a normal control diet (NCD) group, a [...] Read more.
Background: This study investigated the mechanisms underlying diarrhea induced by a high-fat diet (HFD) under a state of fatigue, focusing on gut microbiota dysbiosis, bile acid metabolic disturbance, and gut–liver injury. Methods: Mice were assigned to a normal control diet (NCD) group, a HFD-induced diarrhea under fatigue (HFDM) group, and a HFD-induced diarrhea with aggravated dysbiosis (HFDMA) group. Histopathology, inflammatory factors, intestinal barrier-related proteins, small-intestinal microbiota, and colonic bile acid profiles were assessed, and correlation analyses were performed among gut microbiota, bile acids, and inflammatory factors. Results: Compared with the NCD group, both the HFDM and HFDMA groups showed diarrhea-like and fatigue-like phenotypes, histopathological injury in the small intestine and liver, increased tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) levels, and impaired intestinal barrier function. No significant differences in inflammatory factors were observed between the HFDM and HFDMA groups. Zonula occludens-1 (ZO-1) expression decreased in both model groups but reached statistical significance only in the HFDMA group, whereas Claudin-1 expression was significantly reduced in both groups. Gut microbiota analysis showed altered community structure, with downward trends in alpha diversity that did not reach statistical significance but clear separation trends in beta diversity. Proteobacteria and Streptococcus increased, whereas Ligilactobacillus decreased. Total bile acid levels did not differ significantly among groups; however, the ratio of secondary to primary bile acids was significantly reduced in both model groups, particularly in the HFDMA group, with decreases in representative secondary bile acids, including hyodeoxycholic acid (HDCA) and isolithocholic acid (isoLCA). Correlation analysis further supported close associations among gut microbial alteration, bile acid disturbance, and intestinal and hepatic inflammation. Conclusions: Gut microbiota dysbiosis may disrupt bile acid metabolism, impair intestinal barrier integrity, and promote intestinal and hepatic inflammatory responses, thereby contributing to diarrhea progression under fatigue and HFD conditions through the gut–liver axis. Full article
Show Figures

Figure 1

Review

Jump to: Research

42 pages, 6838 KB  
Review
Medicinal Plant Polysaccharides as Microbiota-Directed Modulators of Immunosenescence: Structural Determinants, Metabolite Reprogramming, and Host Immune Regulation
by Kailang Mu, Meihui He, Ruiqi Liao, Changliu Shao, Pingxuan Xie, Junli Xie, Yuchen Liu, Zhigang Ju, Ke Zhong, Yuan Yuan and Yuxin Pang
Nutrients 2026, 18(16), 2641; https://doi.org/10.3390/nu18162641 - 12 Aug 2026
Viewed by 362
Abstract
Immunosenescence is a major contributor to age-associated morbidity, yet microbiota-directed strategies capable of restoring immune homeostasis remain insufficiently validated. Medicinal plant polysaccharides (MPPs) are structurally diverse macromolecules that often resist host digestion and undergo microbial transformation in the colon, but their effects cannot [...] Read more.
Immunosenescence is a major contributor to age-associated morbidity, yet microbiota-directed strategies capable of restoring immune homeostasis remain insufficiently validated. Medicinal plant polysaccharides (MPPs) are structurally diverse macromolecules that often resist host digestion and undergo microbial transformation in the colon, but their effects cannot be interpreted as those of a homogeneous intervention class. In this structured narrative review, we critically synthesize evidence across structural carbohydrate biology, microbial ecology, metabolite signaling, and immune aging and propose a structure–microbiota–metabolite–immunity framework for evaluating how MPPs may influence immunosenescence. Monosaccharide composition, glycosidic linkages, molecular-weight distribution, branching, uronic acid content, chemical substitutions, and higher-order conformation can shape microbial carbohydrate-active enzyme activity, polysaccharide utilization, and ecological cross-feeding. The resulting changes in short-chain fatty acids, secondary bile acids, tryptophan-derived indoles, and other metabolites may affect epithelial barrier integrity, regulatory T-cell/T helper 17-cell (Treg/Th17) balance, macrophage polarization, nuclear factor-κB (NF-κB) signaling, NLR family pyrin domain-containing 3 (NLRP3) inflammasome activation, and systemic inflammatory tone. However, evidence from in vitro systems and young disease models primarily supports mechanistic plausibility and should not be treated as direct evidence of immunosenescence modification. Translation will require structurally defined preparations, causal validation in aging-relevant models, comparison with established fermentable fibers, identification of responder phenotypes, and adequately powered trials in older adults. Full article
Show Figures

Figure 1

25 pages, 807 KB  
Review
Across Kingdoms: The Bacteriome, Mycobiome, and Virome in Autoimmune Diseases: Mechanistic Insights, Therapeutic Perspectives, and the Emerging Role of COVID-19
by Edit Posta, Eva Gyarmati, Laszlo Majoros, Istvan Fekete, Istvan Varkonyi, Eva Zold and Zsolt Barta
Nutrients 2026, 18(12), 2032; https://doi.org/10.3390/nu18122032 - 22 Jun 2026
Viewed by 1387
Abstract
Autoimmune and immune-mediated inflammatory diseases (IMIDs) develop when genetically and environmentally susceptible hosts lose stable immune tolerance. The gut ecosystem is increasingly recognized as a biologically active interface in this process. Its bacterial, fungal, and viral components may shape mucosal and systemic immunity [...] Read more.
Autoimmune and immune-mediated inflammatory diseases (IMIDs) develop when genetically and environmentally susceptible hosts lose stable immune tolerance. The gut ecosystem is increasingly recognized as a biologically active interface in this process. Its bacterial, fungal, and viral components may shape mucosal and systemic immunity through antigenic stimulation, barrier regulation, and metabolite-dependent signaling, although the strength of evidence is uneven: bacteriome data are currently the most mature, whereas mycobiome, virome, and phageome findings remain more disease-specific and emerging. Dysbiosis may influence autoimmunity through overlapping routes, including epithelial barrier failure, altered short-chain fatty acid, bile acid, and tryptophan metabolism, molecular mimicry, and cross-kingdom microbial interactions. Nutrition is central to this network because dietary substrates determine microbial growth, metabolic output, epithelial integrity, and immune-cell differentiation. In this narrative review, we integrate evidence on disease-associated bacteriome, mycobiome, and virome patterns in systemic autoimmune diseases, with emphasis on rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s syndrome, systemic sclerosis, spondyloarthritis, vasculitides, and idiopathic inflammatory myopathies. COVID-19 is considered not as a proven causal driver of autoimmunity, but as an example of an environmental and infectious insult capable of perturbing microbiome–barrier–immune communication. Finally, we discuss diet-based and microbiome-targeted approaches, including probiotics, prebiotics, synbiotics, and postbiotics, as adjunctive strategies that may help restore microbial resilience and immune balance. A better understanding of the diet–microbiome–host immunity axis may support more personalized preventive and therapeutic concepts in autoimmune disease. Full article
Show Figures

Figure 1

29 pages, 2326 KB  
Review
Effects of Herbal and Natural Product Interventions on Gut Microbiota and Clinical Outcomes in Patients Receiving PPI-Containing Therapy: A Systematic Review and Meta-Analysis
by Ji Hye Hwang and You-Kyung Choi
Nutrients 2026, 18(11), 1792; https://doi.org/10.3390/nu18111792 - 2 Jun 2026
Viewed by 790
Abstract
Proton pump inhibitor (PPI)-containing regimens, including bismuth quadruple therapy, may perturb gut microbiota through combined exposure to acid suppression, antibiotics, bismuth, and underlying disease context. Herbal medicines and natural products have been proposed as adjunctive interventions to mitigate treatment-related microbiota perturbations; however, systematic [...] Read more.
Proton pump inhibitor (PPI)-containing regimens, including bismuth quadruple therapy, may perturb gut microbiota through combined exposure to acid suppression, antibiotics, bismuth, and underlying disease context. Herbal medicines and natural products have been proposed as adjunctive interventions to mitigate treatment-related microbiota perturbations; however, systematic synthesis of the clinical evidence remains limited. This systematic review and meta-analysis evaluated the effects of herbal and natural product interventions on gut microbiota and clinical outcomes in patients receiving PPI-containing therapy. Six databases (PubMed, EMBASE, Web of Science, Scopus, CENTRAL, and CNKI) were searched from their inception to March 2026. Risk of bias was assessed using RoB 2.0 and ROBINS-I. This review was prospectively registered in PROSPERO (CRD420261346672). Eighteen studies (17 randomized controlled trials, 1 observational study; n = 1984 participants) were included in the final analysis. Meta-analysis demonstrated significantly higher Helicobacter pylori eradication rates (pooled relative risk (RR) = 1.20, 95% confidence interval (CI) 1.14–1.27; I2 = 33%). Chinese-style total effective rate was also higher in the herbal groups (RR = 1.19, 95% CI 1.14–1.25; I2 = 0%), but this non-standardized outcome should be interpreted cautiously. Exploratory microbiome meta-analyses suggested higher post-treatment Bifidobacterium and Lactobacillus levels; however, substantial heterogeneity limited interpretability. Narrative synthesis revealed potential preservation of α-diversity and attenuation of pathobiont proliferation in herbal groups. Overall, herbal and natural product interventions may be associated with favorable clinical outcomes and potential microbiota-modulating effects in patients receiving PPI-containing therapy, but certainty remains limited due to methodological concerns, outcome indirectness, and heterogeneity. High-quality trials stratified by antibiotic exposure are warranted. Full article
Show Figures

Figure 1

Back to TopTop