Dear Colleagues,

The human microbiota has gained increasing attention as a possible player contributing to the acquisition and maintenance good of health in humans in addition to disease development. Indeed, these microbial communities, living in equilibrium with the human host, are involved in different physiological functions, including immune system development, tolerance acquisition and mucosal permeability establishment. Accordingly, microbial dysbiosis has been highlighted in several diseases that are not limited to gastrointestinal conditions but extended to other organs that are influenced by local resident microbiota and/or by gut microbiota. These accumulating data are providing novel clues regarding disease pathogenesis and may open the way to the use of microbial signatures as novel biomarkers for diseases monitoring and diagnosis as well as novel targets to develop specific therapies. Nevertheless, most of the current knowledge is based on observational studies: there is a need to move to a more mechanistic approach to unravel the role of the microbial dysbiosis in specific diseases. Technological advances, involving both molecular strategies and bioinformatic tools, will be crucial to further improve metagenomic studies and our comprehension of microbial involvement in human well-being.

In this scenario, Genes has decided to dedicate a Special Issue to the role of the human microbiota in health and disease status that will focus on the most recent advancement in this field and support harmonization and improvement of the outcomes in this important field.

The intent of this Special Issue is to specifically highlight the most recent advances in metagenomic studies reporting not only microbial imbalance in specific diseases but also highlighting the molecular mechanisms linking microbes to the development of various pathologies. Research and review articles on these aspects are encouraged. We invite you to take part in this Special Issue with a scientific contribution. The manuscripts will, as always, be subjected to examination by specialized reviewers to guarantee their scientific acceptability.

Dr. Valeria D’Argenio
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 100 words) can be sent to the Editorial Office for announcement on this website.

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. Genes is an international peer-reviewed open access monthly 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 2400 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.

• microbiota
• metagenomics
• microbiota-related diseases
• microbial dysbiosis
• microbiota manipulation

Title 1: Intestinal microbiota and inflammatory mediators differentiate IgE mediated and non-mediated cases of cow's milk protein at diagnosis

Title 2: Meta-analysis of Multi-functional Biomarkers for Discovery and Predictive Modeling of Colorectal Adenoma and Carcinoma

Abstract: Background: Despite the effectiveness of colonoscopy for reducing colorectal cancer (CRC) mortality, poor screening compliance ranks CRC as the second most deadly malignancy. There is a need to develop a preventative, non-invasive, fecal microbiota diagnostic test for early detection of both pre-cancerous adenomas and carcinomas to reduce mortality. Methods: We conducted a clinical meta-analysis of published deep metagenomic stool sequence datasets including 1,705 subjects from 8 countries, including 703 healthy controls, 196 precancerous colorectal adenoma (CRA), 48 advanced precancerous colorectal adenoma (CRAA) and 758 CRC cases diagnosed by colonoscopy. We analyzed these data through a novel automated machine learning workflow using a two-stage feature importance ranking and ensemble modeling method to identify and select highly predictive taxonomic and functional biomarkers. Results: Machine learning modeling of selected features differentiated the metagenomic profiles of healthy patients from CRA, CRAA and CRC cases with an average area under the curve (AUC) for external holdout testing=0.84 (sensitivity=0.82; specificity=0.71) for CRC; AUC=0.96 (sensitivity=0.78; specificity=0.98) for CRAA; AUC=0.90 (sensitivity=0.72, specificity=0.90) for CRA. Conclusions: Inclusion of gene features improved model performance compared to those generated with taxonomy alone. The predictive features identified for each disease class were largely distinct and represented differing proportions of taxonomic and gene features. Our results emphasize the promise of a non-invasive test of early detection of colorectal adenomas and carcinomas.
Highlights: AI applied of Bid Data Metagenomics Microbiome Colon Cancer Diagnosis