Microbiome in Neuroblastoma: A Virgin Island in the World of Onco-Microbiome

Abstract

The composition of the gut and/or tumor microbiome has been intricately involved in the onset of carcinogenesis, tumor progression, therapy response, and patient outcomes in diverse solid cancers. The microbiome type, composition, and their metabolome have been functionally implicated in the multifarious cellular processes, transformation, proliferation, tumor immune evasion, cellular migration, etc. Despite such compelling evidence on the role of microbiome interactions in cancer, the realization of their role in neuroblastoma (NB), the deadly extracranial tumor in infants is few and fragmentary. This review comprehends the composition, diversity, and significance of microbiota in human health. Further, this review discusses the microbiota composition, their mode of action, and their signaling flow through and cellular processes in diverse cancers including NB. Precisely, this study for the first time has realized the functional relevance and clinical significance of the gut and tumor microbiome for NB. Interestingly, large cohort clinical and preclinical in vivo models of NB realized the following: gut microbiota predicts the risk for NB; postnatal (and or not maternal transmission) microbiome rearrangements; gut microbial effect on NB pathogenesis; tumor-altering gut microbial composition; microbial composition predicts treatment outcomes in NB; prebiotic remedies for stabilizing NB-associated microbial rearrangements; microbial composition in tumor-infiltrating microbiota predicts NB outcomes.

Keywords: dysbiosis; gut microbiota; microbiome; neuroblastoma; pediatric cancer.

Figure 1

Visual Representation of the Human Microbiome Across Body Sites. Human-associated microbial communities exhibit remarkable spatial diversity, with distinct bacterial populations colonizing specific anatomical sites. The lung microbiome, though less dense, primarily contains Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. The oral microbiome, the second largest microbial community, mainly includes Firmicutes, Proteobacteria, Bacteroidetes, Actinobacteria, and Fusobacteria. The human gut microbiome is primarily composed of six dominant phyla—Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, Verrucomicrobia, and Fusobacteria—with Firmicutes and Bacteroidetes being the most abundant. The skin microbiome harbors site-specific microbes from Cyanobacteria, Proteobacteria, Actinobacteria, Bacteroidetes, and Firmicutes.

Figure 2

Interaction of Microbial Pathogens with Cancer Cells. This schematic illustration depicts various microbial pathogens, including viruses, bacteria, and fungi, that may interact with cancer cells. The viral pathogens include Epstein–Barr Virus, Respiratory Syncytial Virus, Ebola virus, and Rift Valley Fever Virus, which may influence the tumor microenvironment through immune modulation and oncogenic properties. The bacterial pathogens consist of F. nucleatum, Veillonella, Staphylococcus epidermidis, Bacillus subtilis, Micrococcus, H. pylori, Escherichia coli, Salmonella, and Bifidobacteria, Peptostreptococcus, Cutibacterium acnes, Akkermansia muciniphila, Staphylococcus aureus, Prevotella, which may contribute to tumor progression and inflammation, or possess probiotic and therapeutic roles. The fungal pathogens, including Aspergillus, C.neoformans, Candida albicans, and Malassezia, can alter immune responses and affect tumor dynamics. These microbial interactions with cancer cells may have significant implications in tumor development, immune evasion, and microbiome-based therapeutic strategies.

Figure 3

Illustrations depict the following: (a) Gut microbiome predicts the risk for NB; (b) Postnatal (and not maternal transmission) programming of microbiome in NB patients; (c) Function of gut microbe on NB pathogenesis; (d) Presence of NB alters gut microbiome composition; (e) Microbial composition predicts treatment outcome in NB (murine model); (f) Prebiotic treatment mitigate NB-induced microbial mayhem; (g) Microbial composition in TME predicts NB outcome.