Research

16 pages, 3842 KiB

Open AccessArticle

Performance of a Shotgun Prediction Model for Colorectal Cancer When Using 16S rRNA Sequencing Data

by Elies Ramon, Mireia Obón-Santacana, Olfat Khannous-Lleiffe, Ester Saus, Toni Gabaldón, Elisabet Guinó, David Bars-Cortina, Gemma Ibáñez-Sanz, Lorena Rodríguez-Alonso, Alfredo Mata, Ana García-Rodríguez and Victor Moreno

Int. J. Mol. Sci. 2024, 25(2), 1181; https://doi.org/10.3390/ijms25021181 - 18 Jan 2024

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Abstract

Colorectal cancer (CRC), the third most common cancer globally, has shown links to disturbed gut microbiota. While significant efforts have been made to establish a microbial signature indicative of CRC using shotgun metagenomic sequencing, the challenge lies in validating this signature with 16S [...] Read more.

Colorectal cancer (CRC), the third most common cancer globally, has shown links to disturbed gut microbiota. While significant efforts have been made to establish a microbial signature indicative of CRC using shotgun metagenomic sequencing, the challenge lies in validating this signature with 16S ribosomal RNA (16S) gene sequencing. The primary obstacle is reconciling the differing outputs of these two methodologies, which often lead to divergent statistical models and conclusions. In this study, we introduce an algorithm designed to bridge this gap by mapping shotgun-derived taxa to their 16S counterparts. This mapping enables us to assess the predictive performance of a shotgun-based microbiome signature using 16S data. Our results demonstrate a reduction in performance when applying the 16S-mapped taxa in the shotgun prediction model, though it retains statistical significance. This suggests that while an exact match between shotgun and 16S data may not yet be feasible, our approach provides a viable method for comparative analysis and validation in the context of CRC-associated microbiome research. Full article

(This article belongs to the Special Issue Microbiota and Cancer 3.0)

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19 pages, 1640 KiB

Open AccessArticle

Gut Microbiota, Metabolome, and Body Composition Signatures of Response to Therapy in Patients with Advanced Melanoma

by Giulia Vandoni, Federica D'Amico, Marco Fabbrini, Luigi Mariani, Sabina Sieri, Amanda Casirati, Lorenza Di Guardo, Michele Del Vecchio, Andrea Anichini, Roberta Mortarini, Francesco Sgambelluri, Giuseppe Celano, Nadia Serale, Maria De Angelis, Patrizia Brigidi, Cecilia Gavazzi and Silvia Turroni

Int. J. Mol. Sci. 2023, 24(14), 11611; https://doi.org/10.3390/ijms241411611 - 18 Jul 2023

Cited by 2 | Viewed by 1577

Abstract

Despite the recent breakthroughs in targeted and immunotherapy for melanoma, the overall survival rate remains low. In recent years, considerable attention has been paid to the gut microbiota and other modifiable patient factors (e.g., diet and body composition), though their role in influencing [...] Read more.

Despite the recent breakthroughs in targeted and immunotherapy for melanoma, the overall survival rate remains low. In recent years, considerable attention has been paid to the gut microbiota and other modifiable patient factors (e.g., diet and body composition), though their role in influencing therapeutic responses has yet to be defined. Here, we characterized a cohort of 31 patients with unresectable IIIC-IV-stage cutaneous melanoma prior to initiation of targeted or first-line immunotherapy via the following methods: (i) fecal microbiome and metabolome via 16S rRNA amplicon sequencing and gas chromatography/mass spectrometry, respectively, and (ii) anthropometry, body composition, nutritional status, physical activity, biochemical parameters, and immunoprofiling. According to our data, patients subsequently classified as responders were obese (i.e., with high body mass index and high levels of total, visceral, subcutaneous, and intramuscular adipose tissue), non-sarcopenic, and enriched in certain fecal taxa (e.g., Phascolarctobacterium) and metabolites (e.g., anethole), which were potentially endowed with immunostimulatory and oncoprotective activities. On the other hand, non-response was associated with increased proportions of Streptococcus, Actinomyces, Veillonella, Dorea, Fusobacterium, higher neutrophil levels (and a higher neutrophil-to-lymphocyte ratio), and higher fecal levels of butyric acid and its esters, which also correlated with decreased survival. This exploratory study provides an integrated list of potential early prognostic biomarkers that could improve the clinical management of patients with advanced melanoma, in particular by guiding the design of adjuvant therapeutic strategies to improve treatment response and support long-term health improvement. Full article

(This article belongs to the Special Issue Microbiota and Cancer 3.0)

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13 pages, 2059 KiB

Open AccessArticle

Vaginal and Cervical Microbiota Composition in Patients with Endometrial Cancer

by Bartłomiej Barczyński, Karolina Frąszczak, Ewelina Grywalska, Jan Kotarski and Izabela Korona-Głowniak

Int. J. Mol. Sci. 2023, 24(9), 8266; https://doi.org/10.3390/ijms24098266 - 05 May 2023

Cited by 4 | Viewed by 1995

Abstract

According to recent data, changes in the vaginal microbiota could affect the risk of gynaecological cancers. Women suffering from endometrial cancer present significant changes in cervicovaginal microbiota composition. The objective of our study was to characterize the cervicovaginal microbiota of women undergoing hysterectomy [...] Read more.

According to recent data, changes in the vaginal microbiota could affect the risk of gynaecological cancers. Women suffering from endometrial cancer present significant changes in cervicovaginal microbiota composition. The objective of our study was to characterize the cervicovaginal microbiota of women undergoing hysterectomy due to benign disease, atypical hyperplasia, and endometrial cancer; The study included 96 patients, who undergone surgical treatment due to benign uterine disease, precancerous endometrial lesion, and endometrial cancer. Quantitative and qualitative real-time PCR analysis of DNA isolated from vaginal fornix and endocervical canal samples was performed to detect the 19 most commonly identified microorganisms, including different Lactobacillus spp., Atopobium, Bifidobacterium, Chlamydia, and Gardnerella; At least one of the tested microorganisms was identified in 88.5% of vaginal and 83.3% of cervical samples. Lactobacillus iners was significantly more frequent in patients with benign condition, whereas Dialister pneumosintes and Mobiluncus curtisii was more frequent in cancer patients; Mobiluncus curtisi and Dialister pneumosintes, which were identified as significantly more common in endometrial cancer vaginal samples, may be considered as potential endometrial cancer co-factors which promote/stimulate carcinogenesis. However, the exact mechanism of such activity remains unexplained and requires further investigations. Full article

(This article belongs to the Special Issue Microbiota and Cancer 3.0)

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Review

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17 pages, 823 KiB

Open AccessReview

Microbiota–Gastric Cancer Interactions and the Potential Influence of Nutritional Therapies

by Pauline Raoul, Valeria Maccauro, Marco Cintoni, Emidio Scarpellini, Gianluca Ianiro, Antonio Gasbarrini, Maria Cristina Mele and Emanuele Rinninella

Int. J. Mol. Sci. 2024, 25(3), 1679; https://doi.org/10.3390/ijms25031679 - 30 Jan 2024

Viewed by 1138

Abstract

Gastric cancer (GC) is one of the most common causes of cancer deaths, and GC treatments represent a large area of research. Although initially regarded as a sterile organ and unsuitable for microbial communities, the discovery of Helicobacter pylori made us realize that some [...] Read more.

Gastric cancer (GC) is one of the most common causes of cancer deaths, and GC treatments represent a large area of research. Although initially regarded as a sterile organ and unsuitable for microbial communities, the discovery of Helicobacter pylori made us realize that some microbes can colonize the stomach. In recent years, growing interest in gastric bacteria has expanded to the gut microbiota and, more recently, to the oral microbiota. Indeed, the oral–gastric–gut microbiota axis may play a crucial role in maintaining homeostasis, while changes in microbiota composition in GC patients can influence clinical outcomes. On the one hand, the microbiota and its metabolites may significantly influence the progression of GC, while anti-GC treatments such as gastrectomy and chemotherapy may significantly impact the oral–gastric–gut microbiota axis of GC patients. In this context, the role of nutritional therapies, including diet, prebiotics, and probiotics, in treating GC should not be underestimated. Wit this review, we aim to highlight the main role of the gastric, oral, and gut microbiota in GC onset and progression, representing potential future biomarkers for early GC detection and a target for efficient nutritional therapies during the course of GC. Full article

(This article belongs to the Special Issue Microbiota and Cancer 3.0)

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20 pages, 1555 KiB

Open AccessReview

Exploring the Role of the Gut and Intratumoral Microbiomes in Tumor Progression and Metastasis

by Aneta Sevcikova, Beata Mladosievicova, Michal Mego and Sona Ciernikova

Int. J. Mol. Sci. 2023, 24(24), 17199; https://doi.org/10.3390/ijms242417199 - 06 Dec 2023

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Abstract

Cancer cell dissemination involves invasion, migration, resistance to stressors in the circulation, extravasation, colonization, and other functions responsible for macroscopic metastases. By enhancing invasiveness, motility, and intravasation, the epithelial-to-mesenchymal transition (EMT) process promotes the generation of circulating tumor cells and their collective migration. [...] Read more.

Cancer cell dissemination involves invasion, migration, resistance to stressors in the circulation, extravasation, colonization, and other functions responsible for macroscopic metastases. By enhancing invasiveness, motility, and intravasation, the epithelial-to-mesenchymal transition (EMT) process promotes the generation of circulating tumor cells and their collective migration. Preclinical and clinical studies have documented intensive crosstalk between the gut microbiome, host organism, and immune system. According to the findings, polymorphic microbes might play diverse roles in tumorigenesis, cancer progression, and therapy response. Microbial imbalances and changes in the levels of bacterial metabolites and toxins promote cancer progression via EMT and angiogenesis. In contrast, a favorable microbial composition, together with microbiota-derived metabolites, such as short-chain fatty acids (SCFAs), can attenuate the processes of tumor initiation, disease progression, and the formation of distant metastases. In this review, we highlight the role of the intratumoral and gut microbiomes in cancer cell invasion, migration, and metastatic ability and outline the potential options for microbiota modulation. As shown in murine models, probiotics inhibited tumor development, reduced tumor volume, and suppressed angiogenesis and metastasis. Moreover, modulation of an unfavorable microbiome might improve efficacy and reduce treatment-related toxicities, bringing clinical benefit to patients with metastatic cancer. Full article

(This article belongs to the Special Issue Microbiota and Cancer 3.0)

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Graphical abstract

29 pages, 2409 KiB

Open AccessReview

How Can the Microbiome Induce Carcinogenesis and Modulate Drug Resistance in Cancer Therapy?

by Inês Mendes and Nuno Vale

Int. J. Mol. Sci. 2023, 24(14), 11855; https://doi.org/10.3390/ijms241411855 - 24 Jul 2023

Cited by 3 | Viewed by 2152

Abstract

Over the years, cancer has been affecting the lives of many people globally and it has become one of the most studied diseases. Despite the efforts to understand the cell mechanisms behind this complex disease, not every patient seems to respond to targeted [...] Read more.

Over the years, cancer has been affecting the lives of many people globally and it has become one of the most studied diseases. Despite the efforts to understand the cell mechanisms behind this complex disease, not every patient seems to respond to targeted therapies or immunotherapies. Drug resistance in cancer is one of the limiting factors contributing to unsuccessful therapies; therefore, understanding how cancer cells acquire this resistance is essential to help cure individuals affected by cancer. Recently, the altered microbiome was observed to be an important hallmark of cancer and therefore it represents a promising topic of cancer research. Our review aims to provide a global perspective of some cancer hallmarks, for instance how genetic and epigenetic modifications may be caused by an altered human microbiome. We also provide information on how an altered human microbiome can lead to cancer development as well as how the microbiome can influence drug resistance and ultimately targeted therapies. This may be useful to develop alternatives for cancer treatment, i.e., future personalized medicine that can help in cases where traditional cancer treatment is unsuccessful. Full article

(This article belongs to the Special Issue Microbiota and Cancer 3.0)

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12 pages, 658 KiB

Open AccessReview

Biotherapy Using Probiotics as Therapeutic Agents to Restore the Gut Microbiota to Relieve Gastrointestinal Tract Inflammation, IBD, IBS and Prevent Induction of Cancer

by Divakar Dahiya and Poonam Singh Nigam

Int. J. Mol. Sci. 2023, 24(6), 5748; https://doi.org/10.3390/ijms24065748 - 17 Mar 2023

Cited by 20 | Viewed by 3537

Abstract

The gut microbiota is composed of several microbial strains with diverse and variable compositions in both healthy and sick people. An undisturbed gut microbiota needs to be sustained in order to perform all physiological, metabolic, and immune functions in a normal way to [...] Read more.

The gut microbiota is composed of several microbial strains with diverse and variable compositions in both healthy and sick people. An undisturbed gut microbiota needs to be sustained in order to perform all physiological, metabolic, and immune functions in a normal way to prevent the development of diseases. This article has reviewed the published information on the issue of disruption of the balance of the gut microbiota. This disruption could be for many reasons, such as microbial infection in the gastrointestinal tract, food poisoning, diarrhoea, chemotherapy, malnutrition, lifestyle, and ageing. If this disruption is not restored to normal, it might cause dysbiosis. Eventually, a gut microbiota interrupted by dysbiosis might initiate several health issues, such as inflammation of the gastrointestinal tract, the induction of cancer, and the progression of a variety of diseases such as irritable bowel syndrome and inflammatory bowel disease. This review concluded that biotherapy is a natural way of using probiotic products, whether in form of food, beverages, or supplements, to restore the gut microbiota disrupted by dysbiosis. Metabolites secreted by the ingested probiotics help to relieve gastrointestinal tract inflammation and can avoid the induction of cancer. Full article

(This article belongs to the Special Issue Microbiota and Cancer 3.0)

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Other

Jump to: Research, Review

11 pages, 1876 KiB

Open AccessHypothesis

Ovarian Microbiota, Ovarian Cancer and the Underestimated Role of HPV

by Massimiliano Cazzaniga, Marco Cardinali, Francesco Di Pierro and Alexander Bertuccioli

Int. J. Mol. Sci. 2022, 23(24), 16019; https://doi.org/10.3390/ijms232416019 - 16 Dec 2022

Cited by 3 | Viewed by 2021

Abstract

In recent years, many studies have highlighted the possible close correlation between human diseases and definite patterns of microbial organisms colonizing various organs. Even at sites traditionally considered sterile, such as the upper female reproductive tract (FRT), it is now well-recognized as hosting [...] Read more.

In recent years, many studies have highlighted the possible close correlation between human diseases and definite patterns of microbial organisms colonizing various organs. Even at sites traditionally considered sterile, such as the upper female reproductive tract (FRT), it is now well-recognized as hosting a low biomass of different bacterial phyla. Additionally, the data from recent studies highlight a possible link between lower and upper FRT dysbiosis with a potential predisposition to cervical and ovarian cancer. Acinetobacter, chlamydia, increased mycoplasma, and lactobacillary scarcity in the upper FRT have all been linked to a predisposition to ovarian cancer. Additionally, a high-diversity vaginal community state type (CST) is linked to the presence and persistence of high-risk human papillomavirus (HPV), resulting in decreased cellular p53 activity and a reduction in the immune activity of T lymphocytes, resulting in cervical and ovarian cancer predisposition. While these findings are still far from being clarified in all aspects, in patients with multiple risk factors for ovarian cancer, a Lactobacillus crispatus treatment with a product with a proven ability to restore a favorable CST should be considered as an add-on therapy. Full article

(This article belongs to the Special Issue Microbiota and Cancer 3.0)

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