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Microorganisms
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Gut Microbiota in Disease, Second Edition
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Gut Microbiota in Disease, Second Edition

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Gut Microbiota".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 19835

Special Issue Editor

Dr. Francesca Romana Ponziani

E-Mail Website
Guest Editor
Internal Medicine and Gastroenterology—Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of the Sacred Heart, Rome, Italy
Interests: gut microbiota; liver disease; hepatocellular carcinoma; liver cirrhosis; nonalcoholic fatty liver disease
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is a continuation of our previous Special Issue, “Gut Microbiota in Disease”.

The gut microbiota is composed of trillions of microorganisms that reside in our digestive system and perform a number of essential functions for human health. In fact, it constitutes the variable part of our genetic equipement; can be influenced by multiple factors, including drugs or diet; and contributes to the metabolism of nutrients, bile acids, and xenobiotics, to the modulation of the host immune system and the systemic inflammatory state, and to the proper functioning of the intestinal barrier. Perturbations of the intestinal microbiota may underlie the pathogenesis of numerous disease processes not only in the digestive tract, but also in the whole organism. Complex alterations in the composition and function of the gut microbiome, collectively defined as dysbiosis, are a crucial point in the progression of pathologies, such as liver cirrhosis, immune-mediated diseases, and neurological disorders. Therefore, the modulation of the gut microbiome becomes fundamental to stop the progression of several diseases andto regulate the response to therapy in some specific contexts, such as in cancer patients who are treated with immunotherapy.

The aim of this Special Issue is to report the latest evidence on the role of the gut microbiome in influencing human health, particularly regarding its contribution in various disease processes, and how its modulation may affect the development and progression of diseases.

Dr. Francesca Romana Ponziani
Guest Editor

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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-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Microorganisms is an international peer-reviewed open access monthly journal published by MDPI.

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Keywords

  • gut microbiome
  • intestinal barrier
  • inflammation
  • immune system
  • antibiotics
  • cancer

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Published Papers (8 papers)

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Research

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13 pages, 315 KiB  
Article
The Archaeome’s Role in Colorectal Cancer: Unveiling the DPANN Group and Investigating Archaeal Functional Signatures
by Nour El Houda Mathlouthi, Imen Belguith, Mariem Yengui, Hamadou Oumarou Hama, Jean-Christophe Lagier, Leila Ammar Keskes, Ghiles Grine and Radhouane Gdoura
Microorganisms 2023, 11(11), 2742; https://doi.org/10.3390/microorganisms11112742 - 10 Nov 2023
Cited by 2 | Viewed by 2088
Abstract
Background and Aims: Gut microbial imbalances are linked to colorectal cancer (CRC), but archaea’s role remains underexplored. Here, using previously published metagenomic data from different populations including Austria, Germany, Italy, Japan, China, and India, we performed bioinformatic and statistical analysis to identify archaeal [...] Read more.
Background and Aims: Gut microbial imbalances are linked to colorectal cancer (CRC), but archaea’s role remains underexplored. Here, using previously published metagenomic data from different populations including Austria, Germany, Italy, Japan, China, and India, we performed bioinformatic and statistical analysis to identify archaeal taxonomic and functional signatures related to CRC. Methods: We analyzed published fecal metagenomic data from 390 subjects, comparing the archaeomes of CRC and healthy individuals. We conducted a biostatistical analysis to investigate the relationship between Candidatus Mancarchaeum acidiphilum (DPANN superphylum) and other archaeal species associated with CRC. Using the Prokka tool, we annotated the data focusing on archaeal genes, subsequently linking them to CRC and mapping them against UniprotKB and GO databases for specific archaeal gene functions. Results: Our analysis identified enrichment of methanogenic archaea in healthy subjects, with an exception for Methanobrevibacter smithii, which correlated with CRC. Notably, CRC showed a strong association with archaeal species, particularly Natrinema sp. J7-2, Ferroglobus placidus, and Candidatus Mancarchaeum acidiphilum. Furthermore, the DPANN archaeon exhibited a significant correlation with other CRC-associated archaea (p < 0.001). Functionally, we found a marked association between MvhB-type polyferredoxin and colorectal cancer. We also highlighted the association of archaeal proteins involved in the biosynthesis of leucine and the galactose metabolism process with the healthy phenotype. Conclusions: The archaeomes of CRC patients show identifiable alterations, including a decline in methanogens and an increase in Halobacteria species. MvhB-type polyferredoxin, linked with CRC and species like Candidatus Mancarchaeum acidiphilum, Natrinema sp. J7-2, and Ferroglobus placidus emerge as potential archaeal biomarkers. Archaeal proteins may also offer gut protection, underscoring archaea’s role in CRC dynamics. Full article
(This article belongs to the Special Issue Gut Microbiota in Disease, Second Edition)
17 pages, 7967 KiB  
Article
Effects of Hypoxemia by Acute High-Altitude Exposure on Human Intestinal Flora and Metabolism
by Ping Qi, Jin Lv, Liu-Hui Bai, Xiang-Dong Yan and Lei Zhang
Microorganisms 2023, 11(9), 2284; https://doi.org/10.3390/microorganisms11092284 - 11 Sep 2023
Cited by 4 | Viewed by 1550
Abstract
This study examined the effects of hypoxemia caused by acute high-altitude hypoxia (AHAH) exposure on the human intestinal flora and its metabolites. The changes in the intestinal flora, metabolism, and erythropoietin content in the AHAH population under altitude hypoxia conditions were comprehensively analyzed [...] Read more.
This study examined the effects of hypoxemia caused by acute high-altitude hypoxia (AHAH) exposure on the human intestinal flora and its metabolites. The changes in the intestinal flora, metabolism, and erythropoietin content in the AHAH population under altitude hypoxia conditions were comprehensively analyzed using 16S rRNA sequencing, metabonomics, and erythropoietin content. The results showed that compared with those in the control group (C group), the flora and metabolites in the hypoxemia group (D group) were altered. We found alterations in the flora according to the metabolic marker tyrosine through random forest and ROC analyses. Fecal and serum metabonomics analyses revealed that microbial metabolites could be absorbed into the blood and participate in human metabolism. Finally, a significant correlation between tyrosine and erythropoietin (EPO) content was found, which shows that human intestinal flora and its metabolites can help to confront altitude stress by regulating EPO levels. Our findings provide new insights into the adaptive mechanism and prevention of AHAH. Full article
(This article belongs to the Special Issue Gut Microbiota in Disease, Second Edition)
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21 pages, 4436 KiB  
Article
Resistance to Diet Induced Visceral Fat Accumulation in C57BL/6NTac Mice Is Associated with an Enriched Lactococcus in the Gut Microbiota and the Phenotype of Immune B Cells in Intestine and Adipose Tissue
by Samnhita Raychaudhuri, Md Shahinozzaman, Si Fan, Opeyemi Ogedengbe, Ujjwol Subedi and Diana N. Obanda
Microorganisms 2023, 11(9), 2153; https://doi.org/10.3390/microorganisms11092153 - 25 Aug 2023
Cited by 1 | Viewed by 1354
Abstract
Humans and rodents exhibit a divergent obesity phenotype where not all individuals exposed to a high calorie diet become obese. We hypothesized that in C57BL/6NTac mice, despite a shared genetic background and diet, variations in individual gut microbiota function, immune cell phenotype in [...] Read more.
Humans and rodents exhibit a divergent obesity phenotype where not all individuals exposed to a high calorie diet become obese. We hypothesized that in C57BL/6NTac mice, despite a shared genetic background and diet, variations in individual gut microbiota function, immune cell phenotype in the intestine and adipose determine predisposition to obesity. From a larger colony fed a high-fat (HF) diet (60% fat), we obtained twenty-four 18–22-week-old C57BL/6NTac mice. Twelve had responded to the diet, had higher body weight and were termed obese prone (OP). The other 12 had retained a lean frame and were termed obese resistant (OR). We singly housed them for three weeks, monitored food intake and determined insulin resistance, fat accumulation, and small intestinal and fecal gut microbial community membership and structure. From the lamina propria and adipose tissue, we determined the population of total and specific subsets of T and B cells. The OP mice with higher fat accumulation and insulin resistance harbored microbial communities with enhanced capacity for processing dietary sugars, lower alpha diversity, greater abundance of Lactobacilli and low abundance of Clostridia and Desulfobacterota. The OR with less fat accumulation retained insulin sensitivity and harbored microbial communities with enhanced capacity for processing and synthesizing amino acids and higher diversity and greater abundance of Lactococcus, Desulfobacterota and class Clostridia. The B cell phenotype in the lamina propria and mesenteric adipose tissue of OR mice was characterized by a higher population of IgA+ cells and B1b IgM+ cells, respectively, compared to the OP. We conclude that variable responses to the HF diet are associated with the function of individuals’ gut microbiota and immune responses in the lamina propria and adipose tissue. Full article
(This article belongs to the Special Issue Gut Microbiota in Disease, Second Edition)
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12 pages, 1766 KiB  
Article
Gastric Microbiota Gender Differences in Subjects with Healthy Stomachs and Autoimmune Atrophic Gastritis
by Giulia Pivetta, Ludovica Dottori, Federico Fontana, Sophia Cingolani, Irene Ligato, Emanuele Dilaghi, Christian Milani, Marco Ventura, Marina Borro, Gianluca Esposito, Bruno Annibale and Edith Lahner
Microorganisms 2023, 11(8), 1938; https://doi.org/10.3390/microorganisms11081938 - 29 Jul 2023
Cited by 4 | Viewed by 1346
Abstract
Gender differences and microbiota are gaining increasing attention. This study aimed to assess gender differences in gastric bacterial microbiota between subjects with healthy stomachs and those with autoimmune atrophic gastritis. This was a post hoc analysis of 52 subjects undergoing gastroscopy for dyspepsia [...] Read more.
Gender differences and microbiota are gaining increasing attention. This study aimed to assess gender differences in gastric bacterial microbiota between subjects with healthy stomachs and those with autoimmune atrophic gastritis. This was a post hoc analysis of 52 subjects undergoing gastroscopy for dyspepsia (57.7% healthy stomach, 42.3% autoimmune atrophic gastritis). Gastric biopsies were obtained for histopathology and genomic DNA extraction. Gastric microbiota were assessed by sequencing the hypervariable regions of the 16SrRNA gene. The bacterial profile at the phylum level was reported as being in relative abundance expressed as 16SrRNA OTUs (>0.5%) and biodiversity calculated as Shannon-diversity index-H. All data were stratified for the female and male gender. Results showed that women with healthy stomachs had a higher gastric bacterial abundance and less microbial diversity compared to men. Likely due to hypochlorhydria and the non-acid intragastric environment, autoimmune atrophic gastritis seems to reset gender differences in gastric bacterial abundance and reduce biodiversity in males, showing a greater extent of dysbiosis in terms of reduced biodiversity in men. Differences between gender on taxa frequency at the phylum and genus level in healthy subjects and autoimmune atrophic gastritis were observed. The impact of these findings on the gender-specific natural history of autoimmune atrophic gastritis remains to be elucidated; in any case, gender differences should deserve attention in gastric microbiota studies. Full article
(This article belongs to the Special Issue Gut Microbiota in Disease, Second Edition)
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Review

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29 pages, 1176 KiB  
Review
Microbiome in Cancer Development and Treatment
by Sona Ciernikova, Aneta Sevcikova, Beata Mladosievicova and Michal Mego
Microorganisms 2024, 12(1), 24; https://doi.org/10.3390/microorganisms12010024 - 22 Dec 2023
Cited by 1 | Viewed by 3781
Abstract
Targeting the microbiome, microbiota-derived metabolites, and related pathways represents a significant challenge in oncology. Microbiome analyses have confirmed the negative impact of cancer treatment on gut homeostasis, resulting in acute dysbiosis and severe complications, including massive inflammatory immune response, mucosal barrier disruption, and [...] Read more.
Targeting the microbiome, microbiota-derived metabolites, and related pathways represents a significant challenge in oncology. Microbiome analyses have confirmed the negative impact of cancer treatment on gut homeostasis, resulting in acute dysbiosis and severe complications, including massive inflammatory immune response, mucosal barrier disruption, and bacterial translocation across the gut epithelium. Moreover, recent studies revealed the relationship between an imbalance in the gut microbiome and treatment-related toxicity. In this review, we provide current insights into the role of the microbiome in tumor development and the impact of gut and tumor microbiomes on chemo- and immunotherapy efficacy, as well as treatment-induced late effects, including cognitive impairment and cardiotoxicity. As discussed, microbiota modulation via probiotic supplementation and fecal microbiota transplantation represents a new trend in cancer patient care, aiming to increase bacterial diversity, alleviate acute and long-term treatment-induced toxicity, and improve the response to various treatment modalities. However, a more detailed understanding of the complex relationship between the microbiome and host can significantly contribute to integrating a microbiome-based approach into clinical practice. Determination of causal correlations might lead to the identification of clinically relevant diagnostic and prognostic microbial biomarkers. Notably, restoration of intestinal homeostasis could contribute to optimizing treatment efficacy and improving cancer patient outcomes. Full article
(This article belongs to the Special Issue Gut Microbiota in Disease, Second Edition)
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14 pages, 794 KiB  
Review
The Low-FODMAP Diet, IBS, and BCFAs: Exploring the Positive, Negative, and Less Desirable Aspects—A Literature Review
by Maroulla D. Nikolaki, Arezina N. Kasti, Konstantinos Katsas, Konstantinos Petsis, Sophia Lambrinou, Vasiliki Patsalidou, Sophia Stamatopoulou, Katerina Karlatira, John Kapolos, Konstantinos Papadimitriou and Konstantinos Triantafyllou
Microorganisms 2023, 11(10), 2387; https://doi.org/10.3390/microorganisms11102387 - 25 Sep 2023
Cited by 3 | Viewed by 2669
Abstract
The literature about the association of branched short-chain fatty acids (BCFAs) and irritable bowel syndrome (IBS) is limited. BCFAs, the bacterial products of the catabolism of branched-chain amino acids, are proposed as markers for colonic protein fermentation. IBS is a gastrointestinal disorder characterized [...] Read more.
The literature about the association of branched short-chain fatty acids (BCFAs) and irritable bowel syndrome (IBS) is limited. BCFAs, the bacterial products of the catabolism of branched-chain amino acids, are proposed as markers for colonic protein fermentation. IBS is a gastrointestinal disorder characterized by low-grade inflammation and intestinal dysbiosis. The low-FODMAP diet (LFD) has increasingly been applied as first-line therapy for managing IBS symptoms, although it decreases the production of short-chain fatty acids (SCFA), well known for their anti-inflammatory action. In parallel, high protein consumption increases BCFAs. Protein fermentation alters the colonic microbiome through nitrogenous metabolites production, known for their detrimental effects on the intestinal barrier promoting inflammation. Purpose: This review aims to explore the role of BCFAs on gut inflammation in patients with IBS and the impact of LFD in BCFAs production. Methods: A literature search was carried out using a combination of terms in scientific databases. Results: The included studies have contradictory findings about how BCFAs affect the intestinal health of IBS patients. Conclusions: Although evidence suggests that BCFAs may play a protective role in gut inflammation, other metabolites of protein fermentation are associated with gut inflammation. Further research is needed in order to clarify how diet protein composition and, consequently, the BCFAs are implicated in IBS pathogenesis or in symptoms management with LFD+. Full article
(This article belongs to the Special Issue Gut Microbiota in Disease, Second Edition)
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28 pages, 1722 KiB  
Review
Probiotic-Derived Bioactive Compounds in Colorectal Cancer Treatment
by Christina Thoda and Maria Touraki
Microorganisms 2023, 11(8), 1898; https://doi.org/10.3390/microorganisms11081898 - 27 Jul 2023
Cited by 6 | Viewed by 4752
Abstract
Colorectal cancer (CRC) is a multifactorial disease with increased morbidity and mortality rates globally. Despite advanced chemotherapeutic approaches for the treatment of CRC, low survival rates due to the regular occurrence of drug resistance and deleterious side effects render the need for alternative [...] Read more.
Colorectal cancer (CRC) is a multifactorial disease with increased morbidity and mortality rates globally. Despite advanced chemotherapeutic approaches for the treatment of CRC, low survival rates due to the regular occurrence of drug resistance and deleterious side effects render the need for alternative anticancer agents imperative. Accumulating evidence supports that gut microbiota imbalance precedes the establishment of carcinogenesis, subsequently contributing to cancer progression and response to anticancer therapy. Manipulation of the gut microbiota composition via the administration of probiotic-derived bioactive compounds has gradually attained the interest of scientific communities as a novel therapeutic strategy for CRC. These compounds encompass miscellaneous metabolic secreted products of probiotics, including bacteriocins, short-chain fatty acids (SCFAs), lactate, exopolysaccharides (EPSs), biosurfactants, and bacterial peptides, with profound anti-inflammatory and antiproliferative properties. This review provides a classification of postbiotic types and a comprehensive summary of the current state of research on their biological role against CRC. It also describes how their intricate interaction with the gut microbiota regulates the proper function of the intestinal barrier, thus eliminating gut dysbiosis and CRC development. Finally, it discusses the future perspectives in precision-medicine approaches as well as the challenges of their synthesis and optimization of administration in clinical studies. Full article
(This article belongs to the Special Issue Gut Microbiota in Disease, Second Edition)
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Other

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18 pages, 1687 KiB  
Systematic Review
The Role of Bifidobacterium in Liver Diseases: A Systematic Review of Next-Generation Sequencing Studies
by Gabriel Henrique Hizo and Pabulo Henrique Rampelotto
Microorganisms 2023, 11(12), 2999; https://doi.org/10.3390/microorganisms11122999 - 17 Dec 2023
Cited by 5 | Viewed by 1753
Abstract
The physiopathology of liver diseases is complex and can be caused by various factors. Bifidobacterium is a bacterial genus commonly found in the human gut microbiome and has been shown to influence the development of different stages of liver diseases significantly. This study [...] Read more.
The physiopathology of liver diseases is complex and can be caused by various factors. Bifidobacterium is a bacterial genus commonly found in the human gut microbiome and has been shown to influence the development of different stages of liver diseases significantly. This study investigated the relationship between the Bifidobacterium genus and liver injury. In this work, we performed a systematic review in major databases using the key terms “Bifidobacterium”, “ALD”, “NAFLD”, “NASH”, “cirrhosis”, and “HCC” to achieve our purpose. In total, 31 articles were selected for analysis. In particular, we focused on studies that used next-generation sequencing (NGS) technologies. The studies focused on assessing Bifidobacterium levels in the diseases and interventional aimed at examining the therapeutic potential of Bifidobacterium in the mentioned conditions. Overall, the abundance of Bifidobacterium was reduced in hepatic pathologies. Low levels of Bifidobacterium were associated with harmful biochemical and physiological parameters, as well as an adverse clinical outcome. However, interventional studies using different drugs and treatments were able to increase the abundance of the genus and improve clinical outcomes. These results strongly support the hypothesis that changes in the abundance of Bifidobacterium significantly influence both the pathophysiology of hepatic diseases and the related clinical outcomes. In addition, our critical assessment of the NGS methods and related statistical analyses employed in each study highlights concerns with the methods used to define the differential abundance of Bifidobacterium, including potential biases and the omission of relevant information. Full article
(This article belongs to the Special Issue Gut Microbiota in Disease, Second Edition)
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