Maya Raman

Potential of probiotics, prebiotics and synbiotics for management of colorectal cancer.

Colorectal Cancer (CRC) is the second leading cause of cancer-related mortality and is the fourth most common malignant neoplasm in USA. Escaping apoptosis and cell mutation are the prime hallmarks of cancer. It is apparent that balancing the network between DNA damage and DNA repair is critical in preventing carcinogenesis. One-third of cancers might be prevented by nutritious healthy diet, maintaining healthy weight and physical activity. In this review, an attempt is made to abridge the role of carcinogen in colorectal cancer establishment and prognosis, where special attention has been paid to food-borne mutagens and functional role of beneficial human gut microbiome in evading cancer. Further the significance of tailor-made prebiotics, probiotics and synbiotics in cancer management by bio-antimutagenic and desmutagenic activity has been elaborated. Probiotic bacteria are live microorganisms that, when administered in adequate amounts, confer a healthy benefit on the host. Prebiotics are a selectively fermentable non-digestible oligosaccharide or ingredient that brings specific changes, both in the composition and/or activity of the gastrointestinal microflora, conferring health benefits. Synbiotics are a combination of probiotic bacteria and the growth promoting prebiotic ingredients that purport “synergism.”

Probiotics, prebiotics and colorectal cancer prevention.

Colorectal cancer (CRC), the third major cause of mortality among various cancer types in United States, has been increasing in developing countries due to varying diet and dietary habits and occupational hazards. Recent evidences showed that composition of gut microbiota could be associated with the development of CRC and other gut dysbiosis. Modulation of gut microbiota by probiotics and prebiotics, either alone or in combination could positively influence the cross-talk between immune system and microbiota, would be beneficial in preventing inflammation and CRC. In this review, role of probiotics and prebiotics in the prevention of CRC has been discussed. Various epidemiological and experimental studies, specifically gut microbiome research has effectively improved the understanding about the role of probiotics and microbial treatment as anticarcinogenic agents. A few human studies support the beneficial effect of probiotics and prebiotics; hence, comprehensive understanding is urgent to realize the clinical applications of probiotics and prebiotics in CRC prevention.

Transport of anionic azo dyes from aqueous solution to gemini surfactant-modified wheat bran: Synchrotron infrared, molecular interaction and adsorption studies

From the view of economic efficiency and technology sustainability, biomass adsorbent has a high potential for pollution control. In the present study, the performance of gemini 12-2-12 surfactant-modified wheat bran (MWB) for the removal of anionic azo dyes from aqueous solution was investigated. A new insight was gained into the modification mechanism through synchrotron-assisted infrared analysis and molecular interaction simulation. The equilibrium and kinetic studies for the adsorption of Acid Red 18 (AR-18), Acid Orange 7 (AO-7) and Acid Black 1 (AB-1) on MWB were conducted. The Langmuir model well fit the adsorption isotherm data. The adsorption kinetics could be described by the pseudo-second-order and intra-particle diffusion models. The results of thermodynamic studies indicated the adsorption of AR-18 and AB-1 onto MWB was endothermic and spontaneous, while the adsorption of AO-7 was exothermic. The optimum pH for the adsorption of anionic azo dyes on MWB was 3. The adsorbed amount of anionic azo dyes onto MWB decreased when NaCl concentration increased from 0 to 0.4molL-1. The potential of modified wheat bran as a suitable adsorbent for the removal of dyes from wastewater was presented in this study. The results can help understand the migration patterns of organic pollutants at wheat bran-water interface.

Biocompatible ι-carrageenan-γ-maghemite nanocomposite for biomedical applications – synthesis, characterization and in vitro anticancer efficacy

BackgroundCarrageenans are naturally occurring hydrophilic, polyanionic polysaccharide bioploymers with wide application in pharmaceutical industries for controlled drug delivery. Magnetic nanoparticles with their exceptional properties enable them to be an ideal candidate for the production of functional nanostructures, thus facilitating them for biomedical applications. The development of novel nanocomposite by coupling the synergistic effects of the sulfated polysaccharide (iota carrageenan) and a magnetic nanoparticle (maghemite) may offer new interesting applications in drug delivery and cancer therapy. The nanocomposite was characterized by ultraviolet–visible spectroscopy, high resolution scanning electron microscopy, dynamic light scattering analysis, Fourier transform infrared spectroscopy and powder XRD to highlight the possible interaction between the two components. Biocompatibility and the anticancer efficacy of the nanocomposite were assayed and analysed in vitro.ResultsResults suggested that iota carrageenans have electrostatically entrapped the maghemite nanoparticles in their sulfate groups. Biocompatibility of the nanocomposite (at different concentrations) against normal cell lines (HEK-293 and L6) was confirmed by MTT assay. Hoechst 33342 and 7-AAD staining studies under fluorescent microscopy revealed that the nanocomposite is able to induce appoptosis as the mode of cell death in human colon cancer cell line (HCT116). Cell apoptosis here is induced by following the ROS-mediated mitochondrial pathway, combined with downregulation of the expression levels of mRNA of XIAP and PARP-1 and upregulation of caspase3, Bcl-2 and Bcl-xL.ConclusionsThis novel nanocomposite is biocompatible with potential properties to serve in magnet aided targeted drug delivery and cancer therapy.

Cyclic β-(1→3) (1→6) glucan/carrageenan hydrogels for wound healing applications

In the present study, cyclic β-(1→3) (1→6)glucan/carrageenan hydrogels (CBG/Car) were prepared and their in vivo wound healing potential in rats and their ability to encapsulate a hydrophobic drug, ciprofloxacin, were studied. CBG increased the porosity of the hydrogels and hence enhanced the cell attachment and proliferation. It also enhanced drug loading, aided sustained release and exhibited good antibacterial activity. The presence of CBG in the hydrogel enhanced the wound healing ability both in vitro in cells as well as in vivo in rats. Full-thickness excision wounds in rats treated with the hydrogel healed faster when compared to the control. These results as well as the inherent immunomodulating properties of CBG suggest that the CBG/Car hydrogels have the potential to be developed as a novel wound dressing material.

Probiotics and Colorectal Cancer

Probiotics are living microbes that when taken in an adequate amount confers a health benefit to the host. Predominant probiotic microorganisms include Lactobacillus spp, Bifidobacterium spp., and Enterococcus spp. The yeast, Saccharomyces boulardii, and other bacterial species like Bacillus and Clostridium butyricum have been studied extensively. Several mechanisms have been proposed for probiosis, mainly attributed to their abilities to strengthen the intestinal barrier, to modulate the host immune system, and to produce antimicrobial compounds. The main therapeutic and health benefits of probiotics include prevention of diarrhea, hypercholesterolemia, and inflammatory bowel disease and improvement in lactose utilization and mineral absorption, anti-Helicobacter pylori activity, and anticancerous activity (ACA). The ACA of probiotic is mainly accredited to the (1) inactivation of cancerogenic compounds, (2) lowering of intestinal pH, (3) modulation and enhancement of the host’s innate immunity through the secretion of anti-inflammatory molecules, (4) alteration of the intestinal microflora, (5) antiproliferative effects via regulation of apoptosis and cell differentiation, and (6) inhibition of tyrosine kinase signaling pathways. Faecalibacterium prausnitzii anti-inflammatory commensal could be used as a potential probiotic against colitis and CRC.

Short-Chain Fatty Acids

Short-chain fatty acids are formed in the colon as a result of microbial fermentation (Bifidobacterium and Lactobacillus) of undigested bioactive carbohydrates, including prebiotics and dietary fiber, and their significant role in orchestrating colon carcinogenesis is of current interest among researchers. Acetate, propionate, and butyrate are the major by-products of SCFA formation. Propionate and butyrate are extensively involved in the cell differentiation, growth arrest, and apoptosis of cancer cells. The anticancer effects of acetate, propionate, and butyrate (molar ratio of approximately 3:1:1) is supported immensely by epidemiological, in vitro and in vivo, studies. The role of lactate has also been considered by several researchers. Diet and dietary habits alter the composition of the gut microflora. An inverse relationship between dietary fiber intake and the incidence of human colon cancer has been observed. Prebiotics and dietary fibers curtail the risk of colon cancer through diverse mechanisms. The interplay between propionate and butyrate, and gastrointestinal epithelial cells (colonocytes) in reducing colon carcinogenesis is a current topic of interest for many researchers. About 70–90 % butyrate is metabolized by the colonocytes. SCFA also modulate colonic and intracellular pH, cell volume, ion transport and regulate cell proliferation, differentiation, and gene expression. Propionate inhibits cell growth and activates apoptosis in colorectal carcinoma cells. Butyrate inhibits histone deacetylase resulting in histone hyperacetylation and growth inhibition in the colonic epithelial cells. This link between histone hyperacetylation, hyperacetylation-induced transcriptional regulation and growth inhibition has been considered as the foremost factors in preventing colon cancer. However, “butyrate paradox,” another concept, has not been confirmed till date. The function of SCFA in the suppression of inflammation and immunomodulation is discussed.

Bioactive Carbohydrate: Prebiotics and Colorectal Cancer

Prebiotics are defined as the indigestible food components that are selectively fermented by the intestinal microbes and promote changes in the gut environment, gut microbial community structure, and their metabolism. Prebiotics have been reported to avert colorectal cancer development by altering the composition and activity of the gut microflora. Administration of prebiotics has been reported to reduce colon cancer and its biomarkers. Oligosaccharides such as inulin, fructo-oligosaccharide, galacto-oligosaccharide, lactulose, soy-oligosaccharide, xylo-oligosaccharide, lactitol, resistant starch, etc., are some of the commercially available prebiotics. Short-chain fructo-oligosaccharides thwart colon carcinogenesis possibly by modulating the colonic ecosystem. Galacto-oligosaccharides, lactulose, and fructo-oligosaccharides are observed to increase the intestinal concentration of lactate, stool frequency, and weight; and decrease fecal concentration of secondary bile acids, fecal pH, and nitroreductase and β-glucuronidase activities, thus preventing colon carcinogenesis. Lactulose is reported to reduce the proliferation and occurrence of adenoma. Resistant starch prevents cancer by modulating gene expression and DNA methylation. Prebiotics undergo fermentation by gut microbes leading to the formation of short-chain fatty acids and enhance the immunity of the host. Butyrate has been observed to have direct effects in preventing colon cancer. Prebiotics are observed to modulate the colonic gut environment and aid in the growth and development of Bifidobacteria spp.

Probiotics and Bioactive Carbohydrates in Colon Cancer Management

The gastrointestinal (GI) system is an important part of the human body involved in digestion. Animals and humans, live in harmony with microbes and establish a symbiotic relationship with them. The human microbiota contains as many as 10 14 bacterial cells, which is ten-fold higher than the number of human cells present in our body. With the development of highthroughput sequencing technique, it is possible to study the gut microbiota and its role in health and disease. It performs a number of essential protective, structural and metabolic functions for host health, including food processing, digestion of complex host-indigestible polysaccharides, pathogen displacement, and synthesis of vitamins. The gut microbiota may exert benefi cial functions beyond the gut such as controlling obesity, gastrointestinal disorders, infl ammatory bowel disease, and irritable bowel syndrome. Also, the altered microbiota has been linked to neuropsychological disorders (depression). The gut microbiota has also been implicated in the development of colorectal cancer (CRC). CRC is one of the major health problems in the world, and the risk factors associated with it are genetic as well as environmental. It evolves through a stepwise accumulation of genetic and epigenetic alterations, leading to the transformation of normal colonic mucosa into invasive cancer. In this chapter, the role of the gut microbiota in health and disease, CRC and its types, prevalence and mechanism are briefl y discussed.

Synbiotics and Colorectal Cancer

Synbiotics are defined as the combination of appropriate probiotics and prebiotics, where the latter form the substrate for the growth and development of selective indigenous or introduce beneficial bacteria in the colon. The prebiotics commonly in use are inulin, fructo-oligosaccharide, galacto-oligosaccharide, lactose, etc., and the probiotics investigated include Bifidobacterium and Lactobacillus spp. Prebiotics form the food for the growth of probiotics. The mechanism of action of synbiotics is a collective effort of pro- and prebiotics. Administration of synbiotics could prevent the initiation or early stage of cancer and also treat the existing tumors. Synbiotic interventions bring about significant alterations in the composition of the colonic microbiome leading to the altered metabolic activity of the organ. It reduces the exposure of cytotoxic agents, including mutagens and carcinogens, to the intestinal lining; decreases cell proliferation in the colonic tissue; and develops mucosal structure. It is reported that administration of synbiotics results in noteworthy changes in the fecal flora, with an increase in Bifidobacterium and Lactobacillus and a reduction in the harmful pathogens such as Clostridium perfringens. These also inhibit the fecal water to cause necrosis in the colonic cells and improve epithelial barrier functions. Synbiotics are also reported to show immunomodulatory effects.