Probiotics in Anticancer Immunity

The mammalian gut is inhabited by more than 100 billion symbiotic microorganisms. The microbial colony residing in the host is recognised as microbiota. One of the critical functions of microbiota is to prevent the intestine against exogenous and harmful pathogen colonization mediated by various mechanistic pathways involving direct competition for limited nutrients and regulation of host immunity. Cancer accounts for one of the leading causes of mortality arising from multifactorial abnormalities. The interconnection of microbiota with various pathological conditions including cancer is recently being researched extensively for analysing tumor induction, progression, inhibition and diagnosis. The diversified microbial colony inhabiting the human gut possesses a vast and distinct metabolic repertoire complementary to the mammalian enzyme activity in the liver as well as gut mucosa which facilitates processes essential for host digestion. Gut microbiota is often considered the critical contributor to defining the biochemical profile of diet thus impacting the health and disease of the hosts. This chapter mainly focuses on understanding the complex microbial interaction with cancer either negatively or positively which may help to conceive novel precautionary and therapeutic strategies to fight cancer.

Gut microbiota plays a significant role in human physiology which includes metabolism, nutrition uptake and immune responses. The imbalance of gut microbiota leads to various disorders or diseases like inflammatory bowel disease, infectious diseases, cancer and obesity. Cancer is one of the major health problems worldwide. Moreover, colorectal cancer (CRC) is the most common cancer in humans which is considered the fourth leading health problem worldwide. The role of probiotics in the regulation of CRC includes enhancement of immune barrier function, intestinal immune state, inhibition of enzymatic activity, cell proliferation and apoptosis, redox homeostasis, and modifying the composition of intestinal microbiota. It can be treated using chemotherapy, radiotherapy, or surgical eradication. However, these treatments may cause the demolition of the intestinal mucosal barrier system as well as dysfunction of the immune system in cancer patients. Hence, biotherapeutic drugs are used along with probiotics and their metabolites viz. polysaccharides, short-chain fatty acids, and inhibitory compounds like proteins and other substances to treat cancer. Lactobacillus rhamnosus GG (LGG) is a widely used probiotic strain in oncology. Also, it has been proven to exert beneficial effects on cancer patients after anticancer therapy. Therapeutic potential of the gut microbiome in cancer treatment via the administration of probiotic supplementations is being investigated using several clinical studies. Probiotic-incorporated biotheraupetic drugs are considered an alternative medicine for various types of cancer. The effectiveness of biotheraupetic drugs mainly depends on the dosage of probiotic strain and their exposure time. However, the mechanism behind the role of probiotics in cancer immunity is unclear so far. The present work summarizes the action of probiotics in anticancer immunity.

Cancer, a condition caused by unregulated cell proliferation, has elevated the global mortality rate that was rising on a daily basis. The treatments for cancer have numerous adverse effects on patients’ lives. To enhance this treatment, probiotics and their metabolites (postbiotics) play an important role in the prevention and treatment of cancer. The mechanisms behind probiotic anti-tumor and/or anti-cancer actions are not yet comprehended. Numerous studies demonstrate that probiotics are useful in cancer prevention and treatment. The majority of which are involved in balancing microbiota, producing essential compounds containing beneficial effects and anti-tumor and cancer activity, preventing pathogen infection, modulating the host immunity, reducing inflammation, and in alleviating the severity of some risk factors. Few studies advise that they should not be used, emphasizing the risk of infection to patients. This chapter provides an overview of skin cancer, skin microbiome, gut microbiome, and its implications in skin cancer, as well as probiotic and postbiotic therapeutic approaches. 

Probiotics are live microorganisms, which confer a health benefit to the host after administering them in adequate amounts. Health benefits of probiotics include antimicrobial activity and gastrointestinal infections, effectiveness against diarrhoea and Helicobacter pylori infection, improvement in lactose metabolism, reduction in serum cholesterol, inflammatory bowel disease, immune system stimulation, antimutagenic properties, and anti-carcinogenic properties. Since probiotics exhibit a positive health impact, many researchers pay attention to the role of probiotics in the enhancement of the immunological response of the host and also in colon cancer prevention and treatment. Probiotic strains, either live or dead cells, belong to the genera Lactobacillus and Bifidobacterium, which are typically evaluated for their immunomodulatory effect on the immune system. These strains can improve the immunological response both in vitro and in vivo. Many mechanisms of probiotics in the prevention and treatment of colon cancer have been proposed. Several studies demonstrate that probiotics and synbiotics exert an anti-carcinogenic effect on colon cancer cells (in vitro) as well as in clinical trials (in vivo). These studies illustrate that probiotics and synbiotics are applied as adjunctive or alternative therapeutic agents for colon cancer management.

Colorectal cancer (CRC) is the third most common cancer, originating in the colon and rectal region, leading to abnormal growth in the colon or rectal region. The gut microbiota plays a critical role in the maintenance of gut homeostasis, and dysbiosis in the gut microbiota has been associated with CRC pathogenesis. Probiotics can manipulate the gut microbiota, which can be effective in CRC treatment. Additionally, probiotics, through the modulation of host immune response, inhibition of tumor growth, reduction of microbial infection, inhibition of cancerogenic compounds, and regulation of apoptosis, can become a novel therapeutic option for the prevention and treatment of CRC. Therefore, this chapter mainly focuses on the mechanisms of probiotics-based anticancer immunity in CRC, so the existing knowledge could help in developing a safe and effective treatment for CRC.

 A growing number of evidence is available in support of the advantageous role of a balanced intestinal microbiota in the progression and manifestation of malignant tumors, not only in the gastrointestinal tract but in other distant tissues as well, with the most potential role in breast carcinoma. Breast cancer involves a complex interplay of several factors, such as familial history, use of hormonal replacement therapy, dietary habits, lifestyle, environment, clinical features, genetics and epigenetics. Recently, a positive correlation between a patient’s breast microbiome and cancer has beocme a novel potential risk factor. In the present chapter, we tried to discuss the role of microbiome as a potential breast cancer risk factor and tried to investigate the literature focussing on the proposed mechanisms behind the interaction of microbiome, human genetic makeup involved in the onset of breast carcinogenesis and determining the effect of transformed breast, milk and gut microbiome on the physiological status of both normal and malignant breast. We also tried to shed light on the resistance to chemotherapeutic treatment among individuals with altered microbiomes with an emphasis on the role of the microbiome in developing and maintaining inflammation, epigenetic alterations and estrogen metabolism. Interestingly, bacterial species are indispensable modulatory agents of widely used chemotherapeutic/ immunotherapeutic regiments. But the exact role of commensal bacteria in immunity, formation of neoplasia and response to treatment needs much more research because most of the available knowledge is based on animal model studies and needs its translation to humans which requires great precision and has various hurdles too. Therefore, we tried to give a comprehensive overview of current knowledge in terms of breast cancer therapeutics and suggest integrating probiotic bacteria and/or modulation of the intestinal microbiota to be used as immune adjuvants, targeting to enhance the effectiveness of conventional anti-tumor treatments and cancer immunotherapies as well.

Stomach cancer is a global health challenge due to its increasing prevalence. The intestinal microbiota of humans plays a vital role in producing short-chain fatty acids, developing resistance towards pathogenic microbes, nutrient absorption, modulation in immunological response, metabolism, synthesis of vitamins, and gut immune system development. Many diseases or disorders, including cancers, obesity, psychiatric illnesses, rheumatoid arthritis, and inflammatory bowel syndrome, are associated with an imbalance of microbiotas. Earlier reports suggest that probiotics via the oral route act as a functional food and suppress cancer development. Further, some probiotics are clinically effective in reducing post-operative inflammation in cancer patients. Probiotics primarily display inhibitory effects against H. pylori infections in the digestive tract. The combination of probiotics with antibiotics has effectively eradicated H. pylori infections. Besides, probiotics reduce the pro-carcinogens metabolism, they also diminish the growth of pathogens and improve the consistency of the intestinal barrier. Moreover, compounds produced by the microorganisms are reported to interact unswervingly with cancer cells and affect their survival. The therapeutic efficacy and adverse side-effects of the strategies used for stomach cancer prevention could be improved by using probiotics either as adjuvant or neo-adjuvant as the safety concern of the commercially used strains has been verified. The underlying mechanism describing microbiota's effect on oncogenic activation, carcinogenic metabolite production, DNA damage, inhibition of tumour immunity, and chronic inflammation induction still needs a more detailed investigation. In addition, doubleblind, placebo-controlled, randomized, and well-designed clinical studies are required to understand the efficacy and mode of action to reduce the death rate and stomach cancer burden. In depth studies are essential to set probiotics as an eccentric strategy for stomach cancer prevention and treatment.

One of the most dreaded outcomes of chronic liver illness is hepatocellular carcinoma (HCC), and it is the most prevalent primary liver cancer. The gut-liver axis has been shown to play a key role in the emergence of chronic liver disorders, including HCC, in recent experimental and clinical studies. The altered gut microbiota is becoming well recognised as an important factor in the progression of chronic liver disorders, such as HCC. Probiotics administration has been proposed as a new, safe and cost-effective strategy for preventing or treating HCC. Probiotics' ability to bind carcinogens, regulation of gut microbiota, improvement of intestinal barrier integrity, and immunomodulation are the mechanisms by which they exert anticancer benefits. This chapter discusses the alterations in gut microbiota linked to HCC and the implications of probiotics and prebiotics for anticancer mechanisms towards HCC.

In the recent past, many investigations have been directed toward finding the possible relationship between probiotic preventive-therapeutic effects and different cancers. Among different cancers, human papillomavirus (HPV)-induced cancer is the third most frequent cancer among women, resulting in being the second cause of death worldwide. Current treatments, such as chemotherapy and radiotherapy, have been shown to have some limitations, and the available effective cervical vaccines are costly, particularly in developing countries. Therefore, the researchers seek alternatives, such as natural components, as a new approach to treating and cure HPVinduced cancer. Among several natural components, probiotics have increasingly gained more attention due to the probiotic-associated immunomodulation and therapeutic efficacy shown in several studies, as well as their lower risk for human health. In this chapter, we have reviewed the association between probiotics and cervical cancer and discussed how probiotics could exert their effects to suppress or even inhibit the growth of cervical tumors, preclinically or clinically. The different aspects of probiotic application have been precisely studied to assess the potential of probiotics in improving or treating HPV-induced cancer. In addition, the effects of probiotics on immune responses have been described.

Among various death-causing diseases, the morbidity and mortality related to cancer are the highest, with millions of new malignancies added to the tally every year and predicted to increase at a higher rate by 2030. Lung cancer is continued to be the leading cause of cancer death worldwide, with a share of 11.6% of all cancers. Since the start of the millennium, there has been a continuous effort to provide the benefits of probiotics in the management and treatment of cancer, particularly lung cancer. Probiotics are defined as “live microorganisms which, when administered in adequate amounts, confer health benefits on the host”. These include specific strains of bacteria and fungi. Bacterial strains belonging to Lactobacillus and Bifidobacterium have demonstrated promising results in the prevention, attenuation, and treatment of the progression of lung cancer. The present chapter focuses on the types and aetiology of lung cancer and the role and mechanism of action of probiotics in providing immunity against lung cancer.

 Every day we are used to hearing about cancer and its effects. Head and neck cancer is one of the types of cancer which is leading to mortality. Treatment of cancer is crucial to lead a happy and healthy life. Till today several medical strategies, such as radiotherapy, chemotherapy, etc., have come forward to eradicate cancer, but along with these approaches, probiotics are also taking part to dissolve this problem. In simple words, probiotics are microorganisms that are present in fermented foods like yogurt, cheese, creams, fermented milk, etc., which, when administered to the host, provide health benefits. Some familiar probiotics are Lactobacillus bulgaricus, L. casei and Streptococcus thermophilus, which are involved in cancer treatment. Much evidence has proven its health benefits. This chapter focuses on how probiotics act on cancer cells with an introduction to head and neck cancer, thereby triggering our interest to probe into further research on treating cancer using probiotics.