Challenges in the production and use of probiotics as therapeuticals in cancer treatment or prevention.
TL;DR: A review of the developments in the area of cancer prevention and treatment, intimately related to advances in the knowledge of the microbiome role in its genesis and therapy is presented in this paper.
Abstract: Probiotics were defined as microbial strains that confer health benefits to their consumers. The concept has evolved during the last twenty years, and today metabolites produced by the strains, known as postbiotics, and even dead cells, known as paraprobiotics are closely associated to them. The isolation of commensal strains from human microbiome has led to the development of next generation probiotics. This review aims to present an overview of the developments in the area of cancer prevention and treatment, intimately related to advances in the knowledge of the microbiome role in its genesis and therapy. Strain identification and characterization, production processes, delivery strategies and clinical evaluation are crucial to translate results into the market with solid scientific support. Examples of recent tools in isolation, strain typification, quality control and development of new probiotic strains are described. Probiotics market and regulation were originally developed in the food sector, but these new strategies will impact the pharmaceutical and health sectors, requiring new considerations in regulatory frameworks.
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TL;DR: The overall data suggest the bio-therapeutic potential of the identified vaginal probiotics against cervical cancer-associated pathogens is higher than previously suggested.
1 citations
TL;DR: The review increases the understanding of the health improvements of mineral-enriched postbiotics, including antioxidant functions, highlighting their perspective on microbial therapy to prevent and threaten gut-related diseases.
Abstract: Postbiotics are non-viable probiotic preparations that confer a health benefit on the host. In the last years, scientific literature has proved that postbiotics have health-promoting features and technological advantages compared to probiotics, augmenting their full potential application in the food and pharmaceutical industries. The current work comprehensively summarizes the benefits and potential applications of postbiotics and essential mineral-enriched biomass and proposes a new strategy for microbial therapy—mineral-enriched postbiotics. We hypothesize and critically review the relationship between micronutrients (calcium, magnesium, iron, zinc, selenium) and postbiotics with gut microbiota, which has been barely explored yet, and how the new approach could be involved in the gut microbiome modulation to prevent and treat gut dysbiosis. Additionally, the bioactive molecules and minerals from postbiotics could influence the host mineral status, directly or through gut microbiota, which increases the mineral bioavailability. The review increases our understanding of the health improvements of mineral-enriched postbiotics, including antioxidant functions, highlighting their perspective on microbial therapy to prevent and threaten gut-related diseases.
1 citations
TL;DR: In this article , a cell proliferation assay and scanning electron microscopy were used to detect changes in the viability of SW480, Caco-2, and HCT-116 colorectal cancer cells treated with plantaricin BM-1.
Abstract: Plantaricin BM-1 is a class IIa bacteriocin produced by Lactobacillus plantarum BM-1 that has significant antimicrobial activity against food-borne bacteria. In this study, a cell proliferation assay and scanning electron microscopy were used to detect changes in the viability of SW480, Caco-2, and HCT-116 colorectal cancer cells treated with plantaricin BM-1. We found that plantaricin BM-1 significantly reduced the viability of all colorectal cancer cell lines tested, especially that of the SW480 cells. Scanning electron microscopy showed that plantaricin BM-1 treatment reduced the number of microvilli and slightly collapsed the morphology of SW480 cells. Fluorescence microscopy and flow cytometry demonstrated that plantaricin BM-1 induced apoptosis of SW480 cells in a concentration-dependent manner. Western blotting further showed that plantaricin BM-1-induced apoptosis of SW480 cells was mediated by the caspase pathway. Finally, transcriptomic analysis showed that 69 genes were differentially expressed after plantaricin BM-1 treatment (p < 0.05), of which 65 were downregulated and four were upregulated. The Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that expression levels of genes involved in the TNF, NF-κB, and MAPK signaling pathways, as well as functional categories such as microRNAs in cancer and transcriptional misregulation in cancer, were affected in SW480 cells following the treatment with plantaricin BM-1. In conclusion, plantaricin BM-1 induced death in SW480 cells via the caspase-dependent apoptosis pathway. Our study provides important information for further development of plantaricin BM-1 for potential applications in anti-colorectal cancer.
01 Jan 2023
01 Jan 2023
TL;DR: In this paper , the authors summarize the involvement of intestinal microbiota in GI cancer development, the potential mechanism of actions of probiotics/prebiotics, and related preclinical and clinical studies in the prevention and treatment of GI cancers to highlight their potential therapeutic values.
Abstract: Gastrointestinal (GI) cancers are major public health problems as they are one of the most common types of cancer worldwide. Despite recent treatment advancements due to a better understanding of the molecular mechanisms of GI cancer tumorigenesis, a high mortality rate still occurs, especially in the metastatic stage of GI cancers. Modulating intestinal microbiota with probiotics and prebiotics becomes a novel strategy for the prevention and treatment of GI cancers as intestinal microbiota has been shown to play a key role in GI cancer development. The literature has provided ample evidence that probiotics could help to prevent or treat GI cancers by slowing down the progression or acting as adjunctive therapy to cancer treatment. In this chapter, we summarize the involvement of intestinal microbiota in GI cancer development, the potential mechanism of actions of probiotics/prebiotics, and related preclinical and clinical studies in the prevention and treatment of GI cancers to highlight their potential therapeutic values.
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TL;DR: An expert panel was convened in October 2013 by the International Scientific Association for Probiotics and Prebiotics (ISAPP) to discuss the field of probiotics and the appropriate use and scope of the term probiotic.
Abstract: An expert panel was convened in October 2013 by the International Scientific Association for Probiotics and Prebiotics (ISAPP) to discuss the field of probiotics. It is now 13 years since the definition of probiotics and 12 years after guidelines were published for regulators, scientists and industry by the Food and Agriculture Organization of the United Nations and the WHO (FAO/WHO). The FAO/WHO definition of a probiotic--"live microorganisms which when administered in adequate amounts confer a health benefit on the host"--was reinforced as relevant and sufficiently accommodating for current and anticipated applications. However, inconsistencies between the FAO/WHO Expert Consultation Report and the FAO/WHO Guidelines were clarified to take into account advances in science and applications. A more precise use of the term 'probiotic' will be useful to guide clinicians and consumers in differentiating the diverse products on the market. This document represents the conclusions of the ISAPP consensus meeting on the appropriate use and scope of the term probiotic.
5,114 citations
TL;DR: Interaction of VeA with at least four methyltransferase proteins indicates a molecular hub function for VeA that questions: Is there a VeA supercomplex or is VeA part of a highly dynamic cellular control network with many different partners?
Abstract: Fungal secondary metabolism has become an important research topic with great biomedical and biotechnological value. In the postgenomic era, understanding the diversity and the molecular control of secondary metabolites are two challenging tasks addressed by the research community. Discovery of the LaeA methyltransferase 10 years ago opened up a new horizon on the control of secondary metabolite research when it was found that expression of many secondary metabolite gene clusters is controlled by LaeA. While the molecular function of LaeA remains an enigma, discovery of the velvet family proteins as interaction partners further extended the role of the LaeA beyond secondary metabolism. The heterotrimeric VelB-VeA-LaeA complex plays important roles in development, sporulation, secondary metabolism and pathogenicity. Recently, three other methyltransferases have been found to associate with the velvet complex, the LaeA-like methyltransferase F (LlmF) and the methyltransferase heterodimers VipC-VapB. Interaction of VeA with at least four methyltransferase proteins indicates a molecular hub function for VeA that questions: Is there a VeA supercomplex or is VeA part of a highly dynamic cellular control network with many different partners?
2,234 citations
TL;DR: A first systematic analysis of microbiota changes in the ileum and colon using multiple diets and investigating both fecal and mucosal samples demonstrates correlations between the microbiota and dysfunctions of gut, adipose tissue, and liver, independent of a specific disease-inducing diet.
Abstract: Development of non-alcoholic fatty liver disease (NAFLD) is linked to obesity, adipose tissue inflammation, and gut dysfunction, all of which depend on diet. So far, studies have mainly focused on diet-related fecal microbiota changes, but other compartments may be more informative on host health. We present a first systematic analysis of microbiota changes in the ileum and colon using multiple diets and investigating both fecal and mucosal samples. Ldlr−/−.Leiden mice received one of three different energy-dense (ED)-diets (n = 15/group) for 15 weeks. All of the ED diets induced obesity and metabolic risk factors, altered short-chain fatty acids (SCFA), and increased gut permeability and NAFLD to various extents. ED diets reduced the diversity of high-abundant bacteria and increased the diversity of low-abundant bacteria in all of the gut compartments. The ED groups showed highly variable, partially overlapping microbiota compositions that differed significantly from chow. Correlation analyses demonstrated that (1) specific groups of bacteria correlate with metabolic risk factors, organ dysfunction, and NAFLD endpoints, (2) colon mucosa had greater predictive value than other compartments, (3) correlating bacteria differed per compartment, and (4) some bacteria correlated with plasma SCFA levels. In conclusion, this comprehensive microbiota analysis demonstrates correlations between the microbiota and dysfunctions of gut, adipose tissue, and liver, independent of a specific disease-inducing diet.
1,097 citations
TL;DR: In this article, a co-regulation between TDC and AGDI pathways in E. faecalis has been investigated and a positive correlation between putrescine biosynthesis and the tyrosine concentration was found.
Abstract: Enterococci are considered mainly responsible for the undesirable accumulation of the biogenic amines (BA) tyramine and putrescine in cheeses. The biosynthesis of tyramine and putrescine has been described as a species trait in Enterococcus faecalis. Tyramine is formed by the decarboxylation of the amino acid tyrosine, by the tyrosine decarboxylase (TDC) route encoded in the tdc cluster. Putrescine is formed from agmatine by the agmatine deiminase (AGDI) pathway encoded in the agdi cluster. These biosynthesis routes have been independently studied, tyrosine and agmatine transcriptionally regulate the tdc and agdi clusters. The objective of the present work is to study the possible co-regulation among TDC and AGDI pathways in E. faecalis. In the presence of agmatine, a positive correlation between putrescine biosynthesis and the tyrosine concentration was found. Transcriptome studies showed that tyrosine induces the transcription of putrescine biosynthesis genes and up-regulates pathways involved in cell growth. The tyrosine modulation over AGDI route was not observed in the mutant Δtdc strain. Fluorescence analyses using gfp as reporter protein revealed PaguB (the promoter of agdi catabolic genes) was induced by tyrosine in the wild-type but not in the mutant strain, confirming that tdc cluster was involved in the tyrosine induction of putrescine biosynthesis. This study also suggests that AguR (the transcriptional regulator of agdi) was implicated in interaction among the two clusters.
838 citations
TL;DR: Novel therapies derived from microbiome studies such as fecal microbiota transplantation, probiotic and prebiotics to target associated diseases have been reviewed to introduce the idea of how certain disease symptoms can be ameliorated through dysbiosis correction, thus revealing a new scientific approach toward disease treatment.
Abstract: Interest toward the human microbiome, particularly gut microbiome has flourished in recent decades owing to the rapidly advancing sequence-based screening and humanized gnotobiotic model in interrogating the dynamic operations of commensal microbiota. Although this field is still at a very preliminary stage, whereby the functional properties of the complex gut microbiome remain less understood, several promising findings have been documented and exhibit great potential toward revolutionizing disease etiology and medical treatments. In this review, the interactions between gut microbiota and the host have been focused on, to provide an overview of the role of gut microbiota and their unique metabolites in conferring host protection against invading pathogen, regulation of diverse host physiological functions including metabolism, development and homeostasis of immunity and the nervous system. We elaborate on how gut microbial imbalance (dysbiosis) may lead to dysfunction of host machineries, thereby contributing to pathogenesis and/or progression toward a broad spectrum of diseases. Some of the most notable diseases namely Clostridium difficile infection (infectious disease), inflammatory bowel disease (intestinal immune-mediated disease), celiac disease (multisystemic autoimmune disorder), obesity (metabolic disease), colorectal cancer, and autism spectrum disorder (neuropsychiatric disorder) have been discussed and delineated along with recent findings. Novel therapies derived from microbiome studies such as fecal microbiota transplantation, probiotic and prebiotics to target associated diseases have been reviewed to introduce the idea of how certain disease symptoms can be ameliorated through dysbiosis correction, thus revealing a new scientific approach toward disease treatment. Toward the end of this review, several research gaps and limitations have been described along with suggested future studies to overcome the current research lacunae. Despite the ongoing debate on whether gut microbiome plays a role in the above-mentioned diseases, we have in this review, gathered evidence showing a potentially far more complex link beyond the unidirectional cause-and-effect relationship between them.
629 citations