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New Insights into Gut Microbiota and Immunity
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New Insights into Gut Microbiota and Immunity

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 April 2025 | Viewed by 9353

Special Issue Editor

Dr. Maria Pascual

E-Mail Website
Guest Editor
Department of Physiology, School of Medicine and Dentistry, University of Valencia, 15 Avda. Blasco Ibanez, 46010 Valencia, Spain
Interests: effects of ethanol on TLR4 immune response; extracellular vesicles; effect of binge drinking in adolescent brain; microbiome; inflammatory response; glial cells
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is the continuation of our previous Special Issues, "Gut Microbiota and Immunity" and "Gut Microbiota and Immunity 2.0". The human gut hosts a wide and diverse ecosystem of microorganisms, termed the microbiota or the novel name “holobiota”. The microbiota is involved in both health and disease, contributing to preventing illness by facilitating metabolism, the immune system, cancer resistance, endocrine signaling, and brain function. However, dysfunctions of the microbiota could lead to gut dysbiosis, leading to alterations in intestinal permeability and the immune system. Innate and adaptive immunity plays an important role in the containment and clearance of microbial pathogens, and new mechanisms have been discovered that can cause or influence systemic immunity alterations in different disorders, such as cancer and autoimmune or neurodegenerative diseases, among others. In this Special Issue, a particular emphasis will be given to the role of the microbiota–gut–brain axis to deepen our knowledge on the mechanisms of gut microbiota–brain communication, including immune signaling and neural–enteroendocrine pathways. We will also review important advances in techniques associated with microbial research, such as DNA sequencing, metabolomics, and proteomics combined with computation-based bioinformatics. Finally, this Special Issue of IJMS will also focus on advances in therapeutic applications, such as, for instance, the usefulness of microbial or chemobiotic applications as promising therapeutic choices to palliate immune-mediated diseases, neurodegenerative disorders, and other syndromes.

Dr. Maria Pascual
Guest Editor

Manuscript Submission Information

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Keywords

  • gut
  • microbiota
  • immune response
  • infectious disease
  • cancer
  • brain function
  • metabolism
  • endocrine signaling
  • pathological conditions
  • therapy

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Published Papers (6 papers)

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Research

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29 pages, 21147 KiB  
Article
Gut-Microbiota-Derived Butyric Acid Overload Contributes to Ileal Mucosal Barrier Damage in Late Phase of Chronic Unpredictable Mild Stress Mice
by Chen Wang, Mei Qiu, Shuo Wang, Jinjin Luo, Ling Huang, Qi Deng, Zhijia Fang, Lijun Sun and Ravi Gooneratne
Int. J. Mol. Sci. 2024, 25(23), 12998; https://doi.org/10.3390/ijms252312998 - 3 Dec 2024
Viewed by 735
Abstract
Intestinal mucosal barrier damage is regarded as the critical factor through which chronic unpredictable mild stress (CUMS) leads to a variety of physical and mental health problems. However, the exact mechanism by which CUMS induces intestinal mucosal barrier damage is unclear. In this [...] Read more.
Intestinal mucosal barrier damage is regarded as the critical factor through which chronic unpredictable mild stress (CUMS) leads to a variety of physical and mental health problems. However, the exact mechanism by which CUMS induces intestinal mucosal barrier damage is unclear. In this study, 14, 28, and 42 d CUMS model mice were established. The indicators related to ileal mucosal barrier damage (IMBD), the composition of the ileal microbiota and its amino acid (AA) and short-chain fatty acid (SCFA) metabolic functions, and free amino acid (FAA) and SCFA levels in the ileal lumen were measured before and after each stress period. The correlations between them are analyzed to investigate how CUMS induces intestinal mucosal barrier damage in male C57BL/6 mice. With the progression of CUMS, butyric acid (BA) levels decreased (14 and 28 d) and then increased (42 d), and IMBD progressively increased. In the late CUMS stage (42 d), the degree of IMBD is most severe and positively correlated with significantly increased BA levels (p < 0.05) in the ileal lumen and negatively correlated with significantly decreased FAAs, such as aspartic, glutamic, alanine, and glycine levels (p < 0.05). In the ileal lumen, the abundance of BA-producing bacteria (Muribaculaceae, Ruminococcus, and Butyricicoccus) and the gene abundance of specific AA degradation and BA production pathways and their related enzymes are significantly increased (p < 0.05). In addition, there is a significant decrease (p < 0.05) in the abundance of core bacteria (Prevotella, Lactobacillus, Turicibacter, Blautia, and Barnesiella) that rely on these specific AAs for growth and/or are sensitive to BA. These changes, in turn, promote further colonization of BA-producing bacteria, exacerbating the over-accumulation of BA in the ileal lumen. These results were validated by ileal microbiota in vitro culture experiments. In summary, in the late CUMS stages, IMBD is related to an excessive accumulation of BA caused by dysbiosis of the ileal microbiota and its overactive AA degradation. Full article
(This article belongs to the Special Issue New Insights into Gut Microbiota and Immunity)
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16 pages, 3844 KiB  
Article
Metagenomics Reveals Sex-Based Differences in Murine Fecal Microbiota Profiles Induced by Chronic Alcohol Consumption
by Manuel Domínguez-Pino, Susana Mellado, Carlos M. Cuesta, Rubén Grillo-Risco, Francisco García-García and María Pascual
Int. J. Mol. Sci. 2024, 25(23), 12534; https://doi.org/10.3390/ijms252312534 - 22 Nov 2024
Viewed by 646
Abstract
Chronic ethanol exposure induces an inflammatory response within the intestinal tract, compromising mucosal and epithelial integrity and leading to dysbiosis of the gut microbiome. However, the specific roles of the gut microbiota in mediating ethanol-induced effects, as well as their interactions with the [...] Read more.
Chronic ethanol exposure induces an inflammatory response within the intestinal tract, compromising mucosal and epithelial integrity and leading to dysbiosis of the gut microbiome. However, the specific roles of the gut microbiota in mediating ethanol-induced effects, as well as their interactions with the immune system, remain poorly characterized. This study aimed to evaluate sex-based differences in fecal microbiota profiles induced by chronic alcohol consumption and to assess whether TLR4 is involved in these effects. We analyzed the 16S rRNA gene sequencing of fecal samples from male and female wild-type (WT) and TLR4-knockout (TLR4-KO) mice with and without chronic ethanol exposure over a three-month period. Our findings provide evidence, for the first time, that male mice are more susceptible to the effects of ethanol on the fecal microbiota, since ethanol exposure induced greater alterations in the Gram-negative and -positive bacteria with immunogenic capacity in the WT male mice than in the female mice. We also demonstrate that the absence of immune receptor TLR4 leads to different microbiota in both sexes, showing anti-inflammatory and protective properties for intestinal barrier function and resulting in a phenotype more resistant to ethanol’s effects. These findings may open new avenues for understanding the relationship between gut microbiota profiles and inflammation in the digestive system induced by chronic alcohol consumption. Full article
(This article belongs to the Special Issue New Insights into Gut Microbiota and Immunity)
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19 pages, 5007 KiB  
Article
Microbial and Metabolic Gut Profiling across Seven Malignancies Identifies Fecal Faecalibacillus intestinalis and Formic Acid as Commonly Altered in Cancer Patients
by Maria Kulecka, Paweł Czarnowski, Aneta Bałabas, Maryla Turkot, Kamila Kruczkowska-Tarantowicz, Natalia Żeber-Lubecka, Michalina Dąbrowska, Ewa Paszkiewicz-Kozik, Jan Walewski, Iwona Ługowska, Hanna Koseła-Paterczyk, Piotr Rutkowski, Anna Kluska, Magdalena Piątkowska, Agnieszka Jagiełło-Gruszfeld, Michał Tenderenda, Cieszymierz Gawiński, Lucjan Wyrwicz, Magdalena Borucka, Maciej Krzakowski, Leszek Zając, Michał Kamiński, Michał Mikula and Jerzy Ostrowskiadd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2024, 25(15), 8026; https://doi.org/10.3390/ijms25158026 - 23 Jul 2024
Cited by 2 | Viewed by 2074
Abstract
The key association between gut dysbiosis and cancer is already known. Here, we used whole-genome shotgun sequencing (WGS) and gas chromatography/mass spectrometry (GC/MS) to conduct metagenomic and metabolomic analyses to identify common and distinct taxonomic configurations among 40, 45, 71, 34, 50, 60, [...] Read more.
The key association between gut dysbiosis and cancer is already known. Here, we used whole-genome shotgun sequencing (WGS) and gas chromatography/mass spectrometry (GC/MS) to conduct metagenomic and metabolomic analyses to identify common and distinct taxonomic configurations among 40, 45, 71, 34, 50, 60, and 40 patients with colorectal cancer, stomach cancer, breast cancer, lung cancer, melanoma, lymphoid neoplasms and acute myeloid leukemia (AML), respectively, and compared the data with those from sex- and age-matched healthy controls (HC). α-diversity differed only between the lymphoid neoplasm and AML groups and their respective HC, while β-diversity differed between all groups and their HC. Of 203 unique species, 179 and 24 were under- and over-represented, respectively, in the case groups compared with HC. Of these, Faecalibacillus intestinalis was under-represented in each of the seven groups studied, Anaerostipes hadrus was under-represented in all but the stomach cancer group, and 22 species were under-represented in the remaining five case groups. There was a marked reduction in the gut microbiome cancer index in all case groups except the AML group. Of the short-chain fatty acids and amino acids tested, the relative concentration of formic acid was significantly higher in each of the case groups than in HC, and the abundance of seven species of Faecalibacterium correlated negatively with most amino acids and formic acid, and positively with the levels of acetic, propanoic, and butanoic acid. We found more differences than similarities between the studied malignancy groups, with large variations in diversity, taxonomic/metabolomic profiles, and functional assignments. While the results obtained may demonstrate trends rather than objective differences that correlate with different types of malignancy, the newly developed gut microbiota cancer index did distinguish most of the cancer cases from HC. We believe that these data are a promising step forward in the search for new diagnostic and predictive tests to assess intestinal dysbiosis among cancer patients. Full article
(This article belongs to the Special Issue New Insights into Gut Microbiota and Immunity)
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13 pages, 1515 KiB  
Article
The Predictive Value of Gut Microbiota Composition for Sustained Immunogenicity following Two Doses of CoronaVac
by Ho-Yu Ng, Yunshi Liao, Ruiqi Zhang, Kwok-Hung Chan, Wai-Pan To, Chun-Him Hui, Wai-Kay Seto, Wai K. Leung, Ivan F. N. Hung, Tommy T. Y. Lam and Ka-Shing Cheung
Int. J. Mol. Sci. 2024, 25(5), 2583; https://doi.org/10.3390/ijms25052583 - 23 Feb 2024
Cited by 1 | Viewed by 1735
Abstract
CoronaVac immunogenicity decreases with time, and we aimed to investigate whether gut microbiota associate with longer-term immunogenicity of CoronaVac. This was a prospective cohort study recruiting two-dose CoronaVac recipients from three centres in Hong Kong. We collected blood samples at baseline and day [...] Read more.
CoronaVac immunogenicity decreases with time, and we aimed to investigate whether gut microbiota associate with longer-term immunogenicity of CoronaVac. This was a prospective cohort study recruiting two-dose CoronaVac recipients from three centres in Hong Kong. We collected blood samples at baseline and day 180 after the first dose and used chemiluminescence immunoassay to test for neutralizing antibodies (NAbs) against the receptor-binding domain (RBD) of wild-type SARS-CoV-2 virus. We performed shotgun metagenomic sequencing performed on baseline stool samples. The primary outcome was the NAb seroconversion rate (seropositivity defined as NAb ≥ 15AU/mL) at day 180. Linear discriminant analysis [LDA] effect size analysis was used to identify putative bacterial species and metabolic pathways. A univariate logistic regression model was used to derive the odds ratio (OR) of seropositivity with bacterial species. Of 119 CoronaVac recipients (median age: 53.4 years [IQR: 47.8–61.3]; male: 39 [32.8%]), only 8 (6.7%) remained seropositive at 6 months after vaccination. Bacteroides uniformis (log10LDA score = 4.39) and Bacteroides eggerthii (log10LDA score = 3.89) were significantly enriched in seropositive than seronegative participants. Seropositivity was associated with B. eggerthii (OR: 5.73; 95% CI: 1.32–29.55; p = 0.022) and B. uniformis with borderline significance (OR: 3.27; 95% CI: 0.73–14.72; p = 0.110). Additionally, B. uniformis was positively correlated with most enriched metabolic pathways in seropositive vaccinees, including the superpathway of adenosine nucleotide de novo biosynthesis I (log10LDA score = 2.88) and II (log10LDA score = 2.91), as well as pathways related to vitamin B biosynthesis, all of which are known to promote immune functions. In conclusion, certain gut bacterial species (B. eggerthii and B. uniformis) and metabolic pathways were associated with longer-term CoronaVac immunogenicity. Full article
(This article belongs to the Special Issue New Insights into Gut Microbiota and Immunity)
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15 pages, 2892 KiB  
Article
Effect of Low Protein Diets Supplemented with Sodium Butyrate, Medium-Chain Fatty Acids, or n-3 Polyunsaturated Fatty Acids on the Growth Performance, Immune Function, and Microbiome of Weaned Piglets
by Wenxue Li, Tianyi Lan, Qi Ding, Zhongxiang Ren, Zhiru Tang, Qingsong Tang, Xie Peng, Yetong Xu and Zhihong Sun
Int. J. Mol. Sci. 2023, 24(24), 17592; https://doi.org/10.3390/ijms242417592 - 18 Dec 2023
Cited by 3 | Viewed by 1620
Abstract
This study aimed to investigate the effects of low-protein (LP) diets supplemented with sodium butyrate (SB), medium-chain fatty acids (MCT), or n-3 polyunsaturated fatty acids (n-3 PUFA) on the growth performance, immune function, and the microbiome of weaned piglets. A total of 120 [...] Read more.
This study aimed to investigate the effects of low-protein (LP) diets supplemented with sodium butyrate (SB), medium-chain fatty acids (MCT), or n-3 polyunsaturated fatty acids (n-3 PUFA) on the growth performance, immune function, and the microbiome of weaned piglets. A total of 120 healthy weaned piglets ((Landrace × Large White × Duroc); 7.93 ± 0.7 kg initial body weight), were randomly divided into five groups. Each group consisted of six replications with four piglets per replication. Dietary treatments included control diet (CON); LP diet (LP); LP + 0.2% SB diet (LP + SB); LP + 0.2% MCT diet (LP + MCT); and LP + PUFA diet (LP + PUFA). The experimental period lasted for 4 weeks. Compared with the CON diet, LP, LP + SB, LP + MCT, and LP + PUFA diets decreased the final weight and average daily gain (ADG) of piglets (p < 0.05). There were lower (p < 0.05) concentrations of IL-8 and higher (p < 0.05) Glutathione peroxidase (GSH-Px) activity in the plasma of piglets fed with LP + SB, LP + MCT, and LP + PUFA diets than those fed with the LP diet. The piglets in the LP + SB and LP + PUFA groups had lower IKK-alpha (IKKa) mRNA expression in the colonic mucosa compared with those in the CON and LP groups (p < 0.05). The mRNA expression of TLR4 in the colonic mucosa of piglets in the LP + SB, LP + MCT, and LP + PUFA groups was decreased when compared with the CON and LP groups (p < 0.05). The LP + MCT diets increased the gene expression of nuclear factor erythroid 2-related factor 2 (Nrf2) in the colonic mucosa of piglets compared with CON, LP, and LP + SB diets (p < 0.05). The abundance of Erysipelotrichaceae in the colonic microbiome of piglets in the LP group was higher than that in the other four groups (p < 0.05). Collectively, this study showed that LP diets supplemented with SB, MCT, or n-3 PUFA reduced plasma inflammatory factor levels, increased plasma GSH-Px activity, and declined mRNA expression of TLR4 and IKKa in the colonic epithelium, whereas it reduced the abundance of Erysipelotrichaceae in the colon of piglets. Full article
(This article belongs to the Special Issue New Insights into Gut Microbiota and Immunity)
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Review

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35 pages, 1351 KiB  
Review
Prenatal Stress and Ethanol Exposure: Microbiota-Induced Immune Dysregulation and Psychiatric Risks
by Rosana Camarini, Priscila Marianno, Maylin Hanampa-Maquera, Samuel dos Santos Oliveira and Niels Olsen Saraiva Câmara
Int. J. Mol. Sci. 2024, 25(18), 9776; https://doi.org/10.3390/ijms25189776 - 10 Sep 2024
Viewed by 1672
Abstract
Changes in maternal gut microbiota due to stress and/or ethanol exposure can have lasting effects on offspring’s health, particularly regarding immunity, inflammation response, and susceptibility to psychiatric disorders. The literature search for this review was conducted using PubMed and Scopus, employing keywords and [...] Read more.
Changes in maternal gut microbiota due to stress and/or ethanol exposure can have lasting effects on offspring’s health, particularly regarding immunity, inflammation response, and susceptibility to psychiatric disorders. The literature search for this review was conducted using PubMed and Scopus, employing keywords and phrases related to maternal stress, ethanol exposure, gut microbiota, microbiome, gut–brain axis, diet, dysbiosis, progesterone, placenta, prenatal development, immunity, inflammation, and depression to identify relevant studies in both preclinical and human research. Only a limited number of reviews were included to support the arguments. The search encompassed studies from the 1990s to the present. This review begins by exploring the role of microbiota in modulating host health and disease. It then examines how disturbances in maternal microbiota can affect the offspring’s immune system. The analysis continues by investigating the interplay between stress and dysbiosis, focusing on how prenatal maternal stress influences both maternal and offspring microbiota and its implications for susceptibility to depression. The review also considers the impact of ethanol consumption on gut dysbiosis, with an emphasis on the effects of prenatal ethanol exposure on both maternal and offspring microbiota. Finally, it is suggested that maternal gut microbiota dysbiosis may be significantly exacerbated by the combined effects of stress and ethanol exposure, leading to immune system dysfunction and chronic inflammation, which could increase the risk of depression in the offspring. These interactions underscore the potential for novel mental health interventions that address the gut–brain axis, especially in relation to maternal and offspring health. Full article
(This article belongs to the Special Issue New Insights into Gut Microbiota and Immunity)
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