Gut Microbiota and Cancer

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16 pages, 3790 KiB

Open AccessArticle

Biomarkers of Immunotherapy Response in Patients with Non-Small-Cell Lung Cancer: Microbiota Composition, Short-Chain Fatty Acids, and Intestinal Permeability

by Alba Moratiel-Pellitero, María Zapata-García, Marta Gascón-Ruiz, Andrea Sesma, Elisa Quílez, Ariel Ramirez-Labrada, Luis Martínez-Lostao, María Pilar Domingo, Patricia Esteban, Alfonso Yubero, Raquel Barbero-Herranz, Ana Moreno-Blanco, José Ramón Paño, Rodrigo Lastra, Julián Pardo, Dolores Isla, Rosa del Campo and Eva Gálvez

Cancers 2024, 16(6), 1144; https://doi.org/10.3390/cancers16061144 - 13 Mar 2024

Viewed by 696

Abstract

Immune checkpoint inhibitors have been proposed as the standard treatment for different stages of non-small-cell lung cancer in multiple indications. Not all patients benefit from these treatments, however, and certain patients develop immune-related adverse events. Although the search for predictors of response to these drugs is a major field of research, these issues have yet to be resolved. It has been postulated that microbiota could play a relevant role in conditioning the response to cancer treatments; however, the human factor of intestinal permeability also needs to be considered as it is closely related to the regulation of host–microbiota interaction. In this article, we analyzed the possible relationship between the response to immune checkpoint inhibitors and the onset of immune-related adverse events, gut microbiota status, and intestinal membrane permeability. In a pioneering step, we also measured short-chain fatty acid content in feces. Although the correlation analyses failed to identify predictive biomarkers, even when all variables were integrated, our patients’ microbial gut ecosystems were rich and diverse, and the intestinal barrier’s integrity was preserved. These results add new knowledge on the composition of microbiota and its correlation with barrier permeability and short-chain fatty acids and suggest that more studies are required before these potential biomarkers can be incorporated into the clinical management of patients via immune checkpoint inhibitor treatment. Full article

(This article belongs to the Topic Gut Microbiota and Cancer)

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20 pages, 3018 KiB

Open AccessArticle

Changes in Intestinal Flora and Serum Metabolites Pre- and Post-Antitumor Drug Therapy in Patients with Non-Small Cell Lung Cancer

by Zhenyu Tian, Yan’e Liu, Dan Zhu, Baoshan Cao and Ming Cui

J. Clin. Med. 2024, 13(2), 529; https://doi.org/10.3390/jcm13020529 - 17 Jan 2024

Viewed by 995

Abstract

Objective: this study aimed to identify the relationships between gut microbiota, metabolism, and non-small cell lung cancer (NSCLC) treatment outcomes, which are presently unclear. Methods: in this single-center prospective cohort study, we investigated changes in the gut microbiota and serum metabolite profile in 60 patients with NSCLC after four cycles of anticancer therapy. Results: The microbial landscape of the gut exhibited a surge in Proteobacteria and Verrucomicrobiota populations, alongside a decline in Firmicutes, Actinobacteriota, and Bacteroidota. Furthermore, a significant shift in the prevalence of certain bacterial genera was noted, with an increase in Escherichia/Shigella and Klebsiella, contrasted by a reduction in Bifidobacterium. Metabolomic analysis uncovered significant changes in lipid abundances, with certain metabolic pathways markedly altered post-treatment. Correlation assessments identified strong links between certain gut microbial genera and serum metabolite concentrations. Despite these findings, a subgroup analysis delineating patient responses to therapy revealed no significant shifts in the gut microbiome’s composition after four cycles of treatment. Conclusions: This study emphasizes the critical role of gut microbiota changes in NSCLC patients during anticancer treatment. These insights pave the way for managing treatment complications and inform future research to improve patient care by understanding and addressing these microbiota changes. Full article

(This article belongs to the Topic Gut Microbiota and Cancer)

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22 pages, 849 KiB

Open AccessReview

The Gut Microbiome from a Biomarker to a Novel Therapeutic Strategy for Immunotherapy Response in Patients with Lung Cancer

by Sreya Duttagupta, Taiki Hakozaki, Bertrand Routy and Meriem Messaoudene

Curr. Oncol. 2023, 30(11), 9406-9427; https://doi.org/10.3390/curroncol30110681 - 24 Oct 2023

Cited by 1 | Viewed by 2552

Abstract

The gastrointestinal microbiome has been shown to play a key role in determining the responses to cancer immunotherapy, including immune checkpoint inhibitor (ICI) therapy and CAR-T. In patients with non-small cell lung cancer (NSCLC), increasing evidence suggests that a microbiome composition signature is associated with clinical response to ICIs as well as with the development of immune-related adverse events. In support of this, antibiotic (ATB)-related dysbiosis has been consistently linked with the deleterious impact of ICI response, shortening the overall survival (OS) among patients on ATBs prior to ICI initiation. In parallel, several preclinical experiments have unravelled various strategies using probiotics, prebiotics, diet, and fecal microbiota transplantation as new therapeutic tools to beneficially shift the microbiome and enhance ICI efficacy. These approaches are currently being evaluated in clinical trials and have achieved encouraging preliminary results. In this article, we reviewed the recent studies on the gut microbiome as a potential biomarker and an adjuvant therapy to ICIs in NSCLC patients. Full article

(This article belongs to the Topic Gut Microbiota and Cancer)

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19 pages, 6402 KiB

Open AccessArticle

Mucosal Microbiome in Patients with Early Bowel Polyps: Inferences from Short-Read and Long-Read 16S rRNA Sequencing

by Zoe Welham, Jun Li, Alexander F. Engel and Mark P. Molloy

Cancers 2023, 15(20), 5045; https://doi.org/10.3390/cancers15205045 - 19 Oct 2023

Viewed by 1116

Abstract

Numerous studies have correlated dysbiosis in stool microbiota with colorectal cancer (CRC); however, fewer studies have investigated the mucosal microbiome in pre-cancerous bowel polyps. The short-read sequencing of variable regions in the 16S rRNA gene has commonly been used to infer bacterial taxonomy, and this has led, in part, to inconsistent findings between studies. Here, we examined mucosal microbiota from patients who presented with one or more polyps, compared to patients with no polyps, at the time of colonoscopy. We evaluated the results obtained using both short-read and PacBio long-read 16S rRNA sequencing. Neither sequencing technology identified significant differences in microbial diversity measures between patients with or without bowel polyps. Differential abundance measures showed that amplicon sequence variants (ASVs) associated with Ruminococcus gnavus and Escherichia coli were elevated in mucosa from polyp patients, while ASVs associated with Parabacteroides merdae, Veillonella nakazawae, and Sutterella wadsworthensis were relatively decreased. Only R. gnavus was consistently identified using both sequencing technologies as being altered between patients with polyps compared to patients without polyps, suggesting differences in technologies and bioinformatics processing impact study findings. Several of the differentially abundant bacteria identified using either sequencing technology are associated with inflammatory bowel diseases despite these patients being excluded from the current study, which suggests that early bowel neoplasia may be associated with a local inflammatory niche. Full article

(This article belongs to the Topic Gut Microbiota and Cancer)

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8 pages, 3901 KiB

Open AccessCase Report

Two Cases of Durable and Deep Responses to Immune Checkpoint Inhibition-Refractory Metastatic Melanoma after Addition of Camu Camu Prebiotic

by Steph A. Pang, Arielle Elkrief, Mariana Pilon Capella and Wilson H. Miller, Jr.

Curr. Oncol. 2023, 30(9), 7852-7859; https://doi.org/10.3390/curroncol30090570 - 25 Aug 2023

Viewed by 2291

Abstract

Camu camu (CC) is a prebiotic that selectively stimulates growth and activity of beneficial gut microbiota. Work in murine models demonstrated that castalagin, the active compound in CC, preferentially binds to beneficial gut microbiome bacteria, promoting a stronger CD8+T cell anti-cancer response. We present two patients with metastatic melanoma whose cancer progressed on immune checkpoint inhibitors (ICIs) and developed clinically significant immune-related adverse events (irAEs). They were rechallenged with ICIs in combination with CC. The first patient is a 71-year-old woman with metastatic melanoma, whose ICI treatment was complicated by immune-related pneumonitis and colitis. Upon progression on maintenance nivolumab, CC was added to nivolumab, leading to a near complete response (CR). The second patient is a 90-year-old man with recurrent unresectable melanoma, treated with nivolumab, complicated by immune-related rash and diabetes. He developed new subcutaneous calf lesions and a metastatic popliteal lymph node. CC was added to nivolumab. One month later, the patient experienced a CR. Both patients have been on nivolumab and CC with durable responses for more than a year, with minimal irAEs. These two cases suggest that CC may modulate the microbiome, synergizing with ICIs to produce deep, durable responses with minimal irAEs. Full article

(This article belongs to the Topic Gut Microbiota and Cancer)

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17 pages, 1234 KiB

Open AccessReview

Evaluation of the Oesophagogastric Cancer-Associated Microbiome: A Systematic Review and Quality Assessment

by Bhamini Vadhwana, Munir Tarazi, Piers R. Boshier and George B. Hanna

Cancers 2023, 15(10), 2668; https://doi.org/10.3390/cancers15102668 - 09 May 2023

Viewed by 1641

Abstract

Objective. Oesophagogastric cancer is the fifth most common cancer worldwide, with poor survival outcomes. The role of bacteria in the pathogenesis of oesophagogastric cancer remains poorly understood. Design. A systematic search identified studies assessing the oesophagogastric cancer microbiome. The primary outcome was to identify bacterial enrichment specific to oesophagogastric cancer. Secondary outcomes included appraisal of the methodology, diagnostic performance of cancer bacteria and the relationship between oral and tissue microbiome. Results. A total of 9295 articles were identified, and 87 studies were selected for analysis. Five genera were enriched in gastric cancer: Lactobacillus, Streptococcus, Prevotella, Fusobacterium and Veillonella. No clear trends were observed in oesophageal adenocarcinoma. Streptococcus, Prevotella and Fusobacterium were abundant in oesophageal squamous cell carcinoma. Functional analysis supports the role of immune cells, localised inflammation and cancer-specific pathways mediating carcinogenesis. STORMS reporting assessment identified experimental deficiencies, considering batch effects and sources of contamination prevalent in low-biomass samples. Conclusions. Functional analysis of cancer pathways can infer tumorigenesis within the cancer–microbe–immune axis. There is evidence that study design, experimental protocols and analytical techniques could be improved to achieve more accurate and representative results. Whole-genome sequencing is recommended to identify key metabolic and functional capabilities of candidate bacteria biomarkers. Full article

(This article belongs to the Topic Gut Microbiota and Cancer)

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10 pages, 1905 KiB

Open AccessCommunication

Antibiotics Significantly Decrease the Survival of Head and Neck Carcinoma Patients with Immunotherapy: A Real-World Analysis of More Than 3000 Cases

by Saskia Preissner, Max Heiland, Robert Preissner, Markus Wirth and Barbara Wollenberg

Cancers 2023, 15(8), 2342; https://doi.org/10.3390/cancers15082342 - 18 Apr 2023

Cited by 1 | Viewed by 1663

Abstract

Objective: The human gut microbiome is strongly influenced by the administration of drugs, namely antibiotics. We hypothesized that the effectiveness of immunotherapy with pembrolizumab in oral squamous cell carcinoma patients is decreased by the administration of antibiotics three months before and after immunotherapy. Methods: We retrieved data from patients diagnosed with head and neck squamous cell carcinoma (HNSCC) (International Classification of Diseases [ICD]-10 codes C00-C14) and receiving immunotherapy with pembrolizumab from the TriNetX network. Two cohorts were built: patients in cohort I did not receive any antibiotics within three months before or up to three months after immunotherapy, while patients in cohort II were administered antibiotics at least once within three months before or after immunotherapy. To exclude confounders, we matched cohorts 1:1 for age, sex, secondary lymph node metastases, nicotine dependence, the insertion of feeding devices, body mass index (BMI) and severe sepsis. After defining the primary outcome as “death”, a Kaplan–Meier analysis was performed, and the risk ratio (RR), odds ratio (OR) and hazard ratio (HR) were calculated. Results: A total of 3651 patients were enrolled, and after matching, each cohort consisted of 1362 patients. Among cohorts I and II, 346 and 511 patients were deceased within one year (risk of death = 25.5 and 38.3%, respectively), whereby the risk difference was significant (p = 0.000; log-rank test). The RR was 0.68 (95% confidence interval: 0.60–0.76), OR was 0.57 (0.48–0.67) and HR was 0.58 (0.51–0.67). Conclusions: Our hypothesis was confirmed: administering antibiotics significantly decreases the drug effectiveness of immunotherapy. We hypothesize that this finding is associated with antibiotic-related changes in the gut microbiome. Prospective clinical studies on the gut microbiome in cancer patients are necessary to understand the complex ecosystem of microbiota during immunotherapy. Trial Registration: Due to the retrospective nature of the study, no registration was necessary. Full article

(This article belongs to the Topic Gut Microbiota and Cancer)

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11 pages, 1555 KiB

Open AccessArticle

Selective Decontamination of the Digestive Tract in Pancreatic Head Resections—A Propensity Score-Matched Analysis

by Olga Radulova-Mauersberger, Florian Oehme, Alexandra Doerell, Laura Frohneberg, Sebastian Hempel, Jürgen Weitz, Thilo Welsch, Marius Distler and Christian Teske

J. Clin. Med. 2023, 12(1), 250; https://doi.org/10.3390/jcm12010250 - 29 Dec 2022

Cited by 1 | Viewed by 1634

Abstract

(1) Background: The postoperative morbidity rate after pancreatic head resection remains high, partly due to infectious complications. The primary aim of this study was to analyze the influence of selective decontamination of the digestive tract (SDD) on the postoperative infection rate after pancreatic surgery. (2) Methods: From January 2019, the standard of care for patients undergoing pancreatic head resections at the Department for Visceral, Thoracic, and Vascular Surgery, University Hospital Dresden was the preoperative oral administration of SDD. The influence of SDD was evaluated for patients operated on between January 2019 and June 2020 in comparison to a propensity score-matched cohort, extracted from an existing database including all pancreatic resections from 2012 to 2018. The primary endpoint of the study was the shift of the bacterial load on the intraoperative bile swab test. The secondary endpoint was the association of SDD with postoperative complications. (3) Results: In total, 200 patients either with SDD (n = 100; 50%) or without SDD (non-SDD, n = 100; 50%) were analyzed. In the patient group without a preoperative biliary stent, 44% (n = 11) of the non-SDD group displayed positive bacterial results, whereas that was the case for only 21.7% (n = 10) in the SDD group (p = 0.05). Particularly, Enterobacter species (spp.) were reduced from 41.2% (n = 14) (non-SDD group) to 23.5% (n = 12) (SDD group) (p = 0.08), and Citrobacter spp. were reduced by 13.7% (p = 0.09) from the non-SDD to the SDD cohort. In patients with a preoperative biliary stent, the Gram-negative Enterobacter spp. were significantly reduced from 52.2% (n = 12) in the non-SDD group to 26.8% (n = 11) in the SDD group (p = 0.04). Similarly, Citrobacter spp. decreased by 20.6% from 30.4% (n = 7) to 9.8% (n = 4) in the non-SDD compared to the SDD group (p = 0.04). In general, deep fluid collection and abscesses occurred more frequently in the non-SDD group (36%; n = 36 vs. 27%; n = 27; p = 0.17). (4) Conclusions: Adoption of SDD before pancreatic head surgery may reduce the bacterial load in bile fluid. SDD administration does not significantly affect the postoperative infectious complication rate after pancreatic head resections. Full article

(This article belongs to the Topic Gut Microbiota and Cancer)

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Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Cancers cancers	5.2	7.4	2009	17.9 Days	CHF 2900	Submit
Current Oncology curroncol	2.6	2.6	1994	18 Days	CHF 2200	Submit
Diseases diseases	3.7	-	2013	18.8 Days	CHF 1800	Submit
Journal of Clinical Medicine jcm	3.9	5.4	2012	17.9 Days	CHF 2600	Submit
Vaccines vaccines	7.8	7.0	2013	19.2 Days	CHF 2700	Submit

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