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Gut Microbiota in Disease and Health 3.0

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

Deadline for manuscript submissions: closed (20 October 2025) | Viewed by 13257

Special Issue Editors


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Guest Editor
1. Microbiota and Cardiovascular Risk Laboratory, Hospital Clínico San Carlos, IdISSC, Madrid, Spain
2. Center for Biomedical Research Network in Cardiovascular Diseases (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain
Interests: gut microbiota; cardiovascular disease; pollution health; biomedicine; platelet; hemostasis

E-Mail Website
Guest Editor
1. Microbiota and Cardiovascular Risk Laboratory, Hospital Clínico San Carlos, Physiology Department, Medical School, Complutense University, IdISSC, Madrid, Spain
2. Center for Biomedical Research Network in Cardiovascular Diseases (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain
Interests: cardiovascular disease; molecular biology; microbiota; atherosclerosis; heart failure; cell signaling
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Special Issue Information

Dear Colleagues,

This Special Issue is a continuation of our previous successful issue “Gut Microbiota in Disease and Health 2.0”.

The gut microbiota is a diverse microbial ecosystem that is dominated by bacteria but also includes populations of fungi, viruses, archaea, and protists. It seems to have coevolved with humans for a mutually beneficial coexistence, being essential in certain complementary metabolic activities that have not fully evolved in the human host. The advent of high-throughput next-generation sequencing platforms, the integration of multi-omics data, and bioinformatics development have accelerated the gaining of knowledge about gut microbial community composition, creating a tremendously shifting our knowledge of physiopathological processes. However, the functions of these communities and how they interact with the host are not fully understood. Since gut bacteria are physically separated from the intestinal epithelium by a mucus layer, without direct interactions between them, the aims of this Special Issue is to delineate the molecular mechanisms by which the gut microbiota affects host metabolism in a paracrine or endocrine manner. We also aim to focus on gut microbiota modulation to promote health and prevent disease. Several strategies have been explored to modulate gut microbiota, from dietary changes, prebiotics, probiotics, antibiotics, to more advanced interventions such as fecal transplantation, bacteriophages, or gene editing therapies. Deepening our knowledge of the molecular mechanisms of gut microbiota/host interactions and emerging modulation strategies offer new opportunities to understand and manipulate the gut microbiota for the benefit of human health.

Dr. Javier Modrego
Dr. Dulcenombre Gómez Garre
Guest Editors

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Keywords

  • microbiota
  • microbiome
  • gut metabolites
  • short-chain fatty acids
  • secondary bile acids
  • microRNA
  • microvesicles
  • cell signaling
  • prebiotics/probiotics
  • nutrition
  • fecal transplantation
  • bacteriophages
  • gene editing

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Published Papers (6 papers)

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Research

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16 pages, 1732 KB  
Article
Octenidine Lozenges Intended for Oral Administration Display In Vitro Activity Against Oropharyngeal Pathogens and Safety Toward Intestinal Microbiota
by Adam Junka, Malwina Brożyna, Paweł Krzyżek, Michał Tomczyk, Krzysztof Krasucki, Tomasz Matys, Tomasz Musiała, Marta Stafiniak and Andrzej Fal
Int. J. Mol. Sci. 2025, 26(20), 10045; https://doi.org/10.3390/ijms262010045 - 15 Oct 2025
Viewed by 150
Abstract
Pharyngitis is a leading cause of outpatient antibiotic use, despite its typically viral or self-limiting nature. Such unnecessary antibiotic therapies are not only the cause of increasing antibiotic resistance, but also significant changes in the human microbiota in the intestines and other locations, [...] Read more.
Pharyngitis is a leading cause of outpatient antibiotic use, despite its typically viral or self-limiting nature. Such unnecessary antibiotic therapies are not only the cause of increasing antibiotic resistance, but also significant changes in the human microbiota in the intestines and other locations, which translate into immune disorders and an increased risk of developing several chronic diseases. Orally administered octenidine-containing lozenges provide a topical alternative; however, their effects on the host microbiota of the oral cavity, throat, and intestine remain unclear. In this study, we evaluated the antimicrobial and antibiofilm in vitro activity of octenidine lozenges against 106 microbial strains, including pathogens and commensals from the oral cavity, pharynx, and large intestine. Minimal biocidal concentrations (MBCs) and minimal biofilm eradication concentrations (MBECs) were determined under physiologically relevant exposure times: 23 min for oral contact and 24 h for intestinal transit. ADME in silico analysis confirmed the lack of absorption of octenidine through the blood–brain barrier and the gastric intestinal mucosa. At concentrations achievable in saliva and the intestinal lumen, octenidine effectively eradicated in vitro all oropharyngeal pathogens while leaving intestinal commensals unaffected. Its impact on oral commensals resembled that of routine mechanical cleaning. These in vitro findings are of high translative value because they support the use of octenidine lozenges as a safe topical treatment for pharyngeal infections, “sore throat”, without adverse effects on the gut microbiota. Full article
(This article belongs to the Special Issue Gut Microbiota in Disease and Health 3.0)
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16 pages, 1748 KB  
Article
Evaluation and Modulation of Gut Microbiome Dysfunction in Chronically Critically Ill Patients: A Prospective Pilot Study
by Ekaterina Chernevskaya, Ekaterina Sorokina, Petr Polyakov, Kirill Gorshkov, Nadezda Kovaleva, Vladislav Zakharchenko and Natalia Beloborodova
Int. J. Mol. Sci. 2025, 26(19), 9778; https://doi.org/10.3390/ijms26199778 - 8 Oct 2025
Viewed by 414
Abstract
Assessing gut microbiota disturbances for subsequent modulation remains a challenge. This study aims to evaluate the safety and efficacy of a microbiota-oriented strategy in treating patients with chronic critical illness (CCI). This single-center prospective study included chronically critically ill patients, stratified into three [...] Read more.
Assessing gut microbiota disturbances for subsequent modulation remains a challenge. This study aims to evaluate the safety and efficacy of a microbiota-oriented strategy in treating patients with chronic critical illness (CCI). This single-center prospective study included chronically critically ill patients, stratified into three groups by severity of microbiota dysfunction. Three different microbiota modulation regimens including metabiotics, enteral, and anaerobic-safe systemic antibiotics were applied subsequently. Forty-three patients with chronic critical illness were included. Mild microbiota dysfunction was present in 49% patients, moderate in 19% and severe in 32%. Monitoring of biomarkers for 14 days confirmed the safety of reducing the pharmacological load in mild to moderate microbiota dysfunction. The microbiota-oriented strategy demonstrated improvements in neurological condition, a decrease in inflammation, and normalization of several hematological and biochemical parameters, without contributing to the activation of opportunistic microorganisms in the intestinal microbiota. The incidence of pneumonia in patients with CCI was reduced significantly during the 28-day observation period. The results of the pilot study suggest the potential benefits of a microbiota-oriented strategy in preventing nosocomial pneumonia in CCI patients. Full article
(This article belongs to the Special Issue Gut Microbiota in Disease and Health 3.0)
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24 pages, 4339 KB  
Article
Delayed Impact of Ionizing Radiation Depends on Sex: Integrative Metagenomics and Metabolomics Analysis of Rodent Colon Content
by Nabarun Chakraborty, Gregory Holmes-Hampton, Matthew Rusling, Vidya P. Kumar, Allison Hoke, Alexander B. Lawrence, Aarti Gautam, Sanchita P. Ghosh and Rasha Hammamieh
Int. J. Mol. Sci. 2025, 26(9), 4227; https://doi.org/10.3390/ijms26094227 - 29 Apr 2025
Cited by 1 | Viewed by 807
Abstract
There is an escalating need to comprehend the long-term impacts of nuclear radiation exposure since the permeation of ionizing radiation has been frequent in our current societal framework. A system evaluation of the microbes that reside inside a host’s colon could meet this [...] Read more.
There is an escalating need to comprehend the long-term impacts of nuclear radiation exposure since the permeation of ionizing radiation has been frequent in our current societal framework. A system evaluation of the microbes that reside inside a host’s colon could meet this knowledge gap since the microbes play major roles in a host’s response to stress. Indeed, our past study suggested that these microbes might break their symbiotic association with moribund hosts to form a pro-survival condition exclusive to themselves. In this study, we undertook metagenomics and metabolomics assays regarding the descending colon content (DCC) of adult mice. DCCs were collected 1 month and 6 months after 7 Gy or 7.5 Gy total body irradiation (TBI). The assessment of the metagenomic diversity profile in DCC found a significant sex bias caused by TBI. Six months after 7.5 Gy TBI, decreased Bacteroidetes were replaced by increased Firmicutes in males, and these alterations were reflected in the functional analysis. For instance, a larger number of networks linked to small chain fatty acid (SCFA) synthesis and metabolism were inhibited in males than in females. Additionally, bioenergy networks showed regression dynamics in females at 6 months post-TBI. Increased accumulation of glucose and pyruvate, which are typical precursors of beneficial SCFAs coupled with the activated networks linked to the production of reactive oxygen species, suggest a cross-sex energy-deprived state. Overall, there was a major chronic adverse implication in male mice that supported the previous literature in suggesting females are more radioresistant than males. The sex-biased chronic effects of TBI should be taken into consideration in designing the pertinent therapeutics. Full article
(This article belongs to the Special Issue Gut Microbiota in Disease and Health 3.0)
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13 pages, 566 KB  
Article
The Association of Short-Chain Fatty Acids with the Occurrence of Gastrointestinal Symptoms in Infants
by Małgorzata Szczuko, Gabriela Duliban, Arleta Drozd, Diana Sochaczewska, Kamila Pokorska-Niewiada and Maciej Ziętek
Int. J. Mol. Sci. 2024, 25(23), 12487; https://doi.org/10.3390/ijms252312487 - 21 Nov 2024
Cited by 1 | Viewed by 2220
Abstract
Short-chain fatty acids (SCFAs) are produced by the fermentation of undigested polysaccharides; they are a group of metabolites resulting from the activity of intestinal bacteria. The main SCFAs are acetic, butyric, propionic, valeric, and caproic acid, and their levels and proportions depend on [...] Read more.
Short-chain fatty acids (SCFAs) are produced by the fermentation of undigested polysaccharides; they are a group of metabolites resulting from the activity of intestinal bacteria. The main SCFAs are acetic, butyric, propionic, valeric, and caproic acid, and their levels and proportions depend on various factors. The aim of this study was to investigate the relationship between the concentration of SCFAs and the occurrence of specific gastrointestinal symptoms in infants. This study was conducted using faecal samples obtained at 1, 3, 6, and 12 months of age. The SCFA content was measured using gas chromatography. At 1 month, an association was found between butyric acid and flatulence. At 3 months, an association was found between butyric acid and flatulence/gas and between 3,4-methylovaleric acid and mucus in the stool. At 6 months, an association was found between butyric and valeric acids and flatulence. By 12 months, the gastrointestinal symptoms had decreased significantly. This study confirms that there is an association between SCFA levels and the presence of bloating, gas, mucus in the stool, and constipation in the gastrointestinal tract. Higher levels of butyric and valeric acids may lead to an increase in troublesome symptoms, such as flatulence and gas, in the first few months of life but are not associated with the occurrence of intestinal colic. The level of 3,4-methylovaleric acid is associated with the presence of allergies, whereas a decrease in acetic acid and an increase in isovaleric acid may exacerbate defecation problems in infants. Full article
(This article belongs to the Special Issue Gut Microbiota in Disease and Health 3.0)
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22 pages, 1813 KB  
Article
Identification of SIBO Subtypes along with Nutritional Status and Diet as Key Elements of SIBO Therapy
by Justyna Paulina Wielgosz-Grochowska, Nicole Domanski and Małgorzata Ewa Drywień
Int. J. Mol. Sci. 2024, 25(13), 7341; https://doi.org/10.3390/ijms25137341 - 4 Jul 2024
Cited by 6 | Viewed by 8490
Abstract
Small intestinal bacterial overgrowth (SIBO) is a pathology of the small intestine and may predispose individuals to various nutritional deficiencies. Little is known about whether specific subtypes of SIBO, such as the hydrogen-dominant (H+), methane-dominant (M+), or hydrogen/methane–dominant (H+/M+), impact nutritional status and [...] Read more.
Small intestinal bacterial overgrowth (SIBO) is a pathology of the small intestine and may predispose individuals to various nutritional deficiencies. Little is known about whether specific subtypes of SIBO, such as the hydrogen-dominant (H+), methane-dominant (M+), or hydrogen/methane–dominant (H+/M+), impact nutritional status and dietary intake in SIBO patients. The aim of this study was to investigate possible correlations between biochemical parameters, dietary nutrient intake, and distinct SIBO subtypes. This observational study included 67 patients who were newly diagnosed with SIBO. Biochemical parameters and diet were studied utilizing laboratory tests and food records, respectively. The H+/M+ group was associated with low serum vitamin D (p < 0.001), low serum ferritin (p = 0.001) and low fiber intake (p = 0.001). The M+ group was correlated with high serum folic acid (p = 0.002) and low intakes of fiber (p = 0.001) and lactose (p = 0.002). The H+ group was associated with low lactose intake (p = 0.027). These results suggest that the subtype of SIBO may have varying effects on dietary intake, leading to a range of biochemical deficiencies. Conversely, specific dietary patterns may predispose one to the development of a SIBO subtype. The assessment of nutritional status and diet, along with the diagnosis of SIBO subtypes, are believed to be key components of SIBO therapy. Full article
(This article belongs to the Special Issue Gut Microbiota in Disease and Health 3.0)
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Review

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34 pages, 2288 KB  
Review
Microbiome and Long COVID-19: Current Evidence and Insights
by Olga A. Caliman-Sturdza, Sevag Hamamah, Oana C. Iatcu, Andrei Lobiuc, Anca Bosancu and Mihai Covasa
Int. J. Mol. Sci. 2025, 26(20), 10120; https://doi.org/10.3390/ijms262010120 - 17 Oct 2025
Viewed by 298
Abstract
Long COVID, also referred to as post-acute sequelae of SARS-CoV-2 infection (PASC), is characterized by persistent multi-systemic symptoms such as fatigue, cognitive impairment, and respiratory dysfunction. Accumulating evidence indicates that gut and oral microbiota play an important role in its pathogenesis. Patients with [...] Read more.
Long COVID, also referred to as post-acute sequelae of SARS-CoV-2 infection (PASC), is characterized by persistent multi-systemic symptoms such as fatigue, cognitive impairment, and respiratory dysfunction. Accumulating evidence indicates that gut and oral microbiota play an important role in its pathogenesis. Patients with long COVID consistently exhibit reduced microbial diversity, depletion of beneficial short-chain fatty acid (SCFA)-producing species such as Faecalibacterium prausnitzii and Bifidobacterium spp. and enrichment of proinflammatory taxa including Ruminococcus gnavus, Bacteroides vulgatus, and Veillonella. These alterations may disrupt intestinal barrier integrity, sustain low-grade systemic inflammation, and influence host immune and neuroendocrine pathways through the gut–brain and gut–lung axes. Distinct microbial signatures have also been associated with symptom clusters, including neuropsychiatric, respiratory, and gastrointestinal manifestations. Proposed mechanisms linking dysbiosis to long COVID include impaired SCFA metabolism, tryptophan depletion, microbial translocation, and interactions with host immune and inflammatory responses, including autoantibody formation and viral antigen persistence. Preliminary interventional studies using probiotics, synbiotics, and fecal microbiota transplantation suggest that microbiome-targeted therapies may alleviate symptoms, although evidence remains limited and heterogeneous. This review synthesizes current literature on the role of gut and oral microbiota in long COVID, highlights emerging microbial biomarkers, and discusses therapeutic implications. While causality remains to be firmly established, restoring microbial balance represents a promising avenue for diagnosis, prevention, and management of long COVID. Full article
(This article belongs to the Special Issue Gut Microbiota in Disease and Health 3.0)
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