Patients with inflammatory bowel disease have a significantly increased risk of developing CRC, while long-term aspirin treatment is associated with a significantly decreased risk of CRC. The mechanisms by which chronic inflammation promotes tumor development often involve the immune system. For example, the IL6/STAT pathway discussed earlier is also implicated in cancer formation. Overexpression of IL6 leads to excess STAT3 transcription, causing unwanted cell proliferation not only in T cells but also in the intestinal epithelium. Another inflammatory cytokine of note is TNF α. While the intestinal bacteria can promote inflammation, they may also affect the likelihood of CRC more directly. Once the intestinal mucus layer is thinned, and direct bacterial-epithelial cell interactions occur, certain bacterial strains promote tumor development. E. coli strains bearing the pks island are of particular interest. This genetic locus codes for the secondary metabolite colibactin, along with the enzymes necessary for its production. Colibactin has been shown to crosslink with DNA, producing double-stranded breaks. Furthermore, pks+ E. coli strains have been shown to be prevalent in CRC patients. In one study, big round plant pot nearly two-thirds of CRC patients had pks+ E. coli strains in their intestinal bacteria. In the same study, pks+ E. coli also existed in about 20 percent of healthy individuals.
Colibactin, however, is a reactive and short-lived protein, requiringclose contact with epithelial cells to cause DNA damage. A healthy mucosal barrier keeps colibactin at a distance and reduces the chance of affecting the intestinal epithelium. Evidence for the pathogenic relationship between diets, Fusobacterium nucleatum, and CRC has been emerging. The F. nucleatum levels have been shown to be higher in CRC than in adjacent normal mucosa. Utilizing the molecular pathological epidemiology paradigm and methods, a recent study has shown the association of fiber-rich diets with decreased risk of F. nucleatum-detectable CRC, but not that of F. nucleatum-undetectable CRC. Experimental evidence supports a carcinogenic role of F. nucleatum, as well as its role in modifying therapeutic outcomes. The amount of F. nucleatum in CRC tissue has been associated with proximal tumor location, CpG island methylator phenotype , microsatellite instability , low-level CD3+ T cell infiltrate, high-level macrophage infiltration, and unfavorable patient survival. The amount of F. nucleatum in average increased in CRC from rectum to cecum, supporting the colorectal continuum model. Future studies should examine the role of diets, microbiota, and CRC in detailed tumor locations. Dietary prevention of CRC, then, has two intertwined aims: to reduce inflammation and to promote a healthy intestinal microbiota. As already discussed, preclinical evidence implies that dietary bio-active compounds, particularly anthocyanins, can reduce symptoms of lowgrade chronic inflammation as well as oxidative stress. It can also aid in balancing the intestinal microbiota by promoting the growth of beneficial bacteria and by reducing the populations of pro-inflammatory bacteria.
Clinical trials have had mixed results, but anthocyanins and some polyphenols have shown to counteract against CRC actively. More research, however, is necessary for conclusive results. How, then, are individuals to consume enough bio-active compounds to have an effect on health? Some answers may be found in the food consumption practices of cultures with historically low CRC incidence. Parts of India, for example, have had some of the lowest CRC incidence rates in the world; however, this status has been changing. In recent decades, increasing urbanization and similar factors have led to progressively Westernized diet patterns and lifestyle. CRC incidence rates are similarly rising, lending weight to the hypothesis that the traditional Indian diet may help prevent CRC. Furthermore, Indian immigrants to Western countries have a much higher incidence of CRC compared to Indians in India. Typical components of traditional Indian meals include a broad variety of flavors, as promoted in Ayurvedic medicine, and a variety of other foods. Both are facilitated by using a thali platter to serve the meal. The traditional American main meal includes an entree , one or more carbohydrates , and one or more vegetables. This basic structure can potentially be adapted with inspiration from thali meals by reducing the size of the main dish and serving more vegetables, legumes, pulses, herbs, and spices to accompany it. The inclusion of multiple colors in a meal is desirable, because certain bio-active compounds, particularly anthocyanins are also pigments. Blue, purple, and red-purple colors in plant foods indicate high anthocyanin content. Purple-pigmented potatoes can be prepared in the same way as traditional white potatoes, but the anthocyanin content is significantly higher in the pigmented varieties.
Purple sweet potatoes also contain more anthocyanins than the more common orange varieties and can be easily substituted for them. Other vegetables with red or purple cultivars include carrots, cauliflower, and cabbage. Different colors can indicate the presence of other bio-active compounds, such as orange , yellow , and red/pink . Thus, healthy bio-active compound consumption may be increased by selecting colorful vegetables. Another way to increase consumption of bio-active compounds is to increase their presence in available foods. The content of bio-active compounds in plant foods is highly influenced by genetics. The agricultural industry could greatly impact health by adopting food plant cultivars that produce bio-active compounds in larger amounts than is currently common. New cultivars may need to be developed that retain desirable characteristics such as large size, pest resistance, reduced spoilage, etc., but also have high bio-active content at the time of consumption. bio-active compounds, with some exceptions, tend to deteriorate during storage. Even when compounds have not deteriorated, storage may reduce the anti-inflammatory/antioxidant activity of bio-active compounds to affect health. A second systemic change that would promote increased bio-active compound consumption involves reworking how fruits and vegetables are currently stored and processed, as well as reducing the average storage time and adapting processing to optimize the amount of bio-active compounds. Presently, “nutritional adequacy” does not consider many of the bio-active compounds discussed in this paper. Further clinical studies are needed to support and elucidate the role of bio-active compounds in the prevention and treatment of disease.Recent research provides preclinical evidence that phytochemicals, especially anthocyanins, promote gut microbial health, reduce inflammation, and lower the risk of colorectal cancer. Clinical evidence is sparse but indicates that anthocyanins and other bio-active compounds do have an effect on colon cancer. Both are consistent with low cancer rates in India, where both traditional diet and Ayurvedic medicine promote consumption of many classes of phytochemicals. Long-term, diet-based randomized clinical trials are both difficult to conduct and prohibitively expensive. However, given the strong evidence from basic studies, observational data, and randomized clinical studies with short-term surrogate outcomes, steps should still be taken to improve the consumption of bio-active compounds, particularly in countries which contain a large proportion of CRC patients. Eating a wide variety of plant foods has no ill effects, and is indeed a commonly recommended part of a healthy lifestyle. Increasing bio-active intake among Westerners will require modifications in both individual eating habits and food system practices.Survival of humans will depend on increased agricultural productivity. Agricultural productivity is not only more yield per area, but also higher nutritional content, round plant pot less dependence on fertilizers, and more resilience against environmental hazards. All of these traits impinge upon plant metabolism. Plants carry out a myriad of metabolic reactions that are intricately connected into complex networks. To understand and engineer plant metabolism, it is important that metabolic complements of plant genomes are accurately and consistently annotated across species. To provide the research community with comprehensive information about plant small-molecule metabolism, we previously introduced the Plant Metabolic Network , a plant-specific online resource of metabolic databases .
PMN consists of PlantCyc, a database of all experimentally-supported information found in the literature from any plant species, as well as 22 single-species databases with a mix of experimentally-supported and computationally-predicted information, which allow researchers to explore each species’ unique metabolism. Here we describe the substantial expansion of PMN in both quantity and quality, which includes 126 single-species databases. We demonstrate the utility of the PMN resource by applying recently published omics data to gain insights into plant physiology and cellular level metabolism. Additionally, we systematically compare 126 species in the context of metabolism to identify metabolic domains and pathways that distinguish plant families. Finally, we present new website tools for viewing and analyzing metabolic data including a CoExpression Viewer and subcellular boundaries for metabolic pathways.PMN is a compendium of databases for plant metabolism with a substantial amount of experimentally supported information. The latest release contains 126 databases of organism-specific genome-scale information of small-molecule metabolism alongside the pan-plant reference database PlantCyc . Together, these databases include 1,280 pathways, of which 1,163 have direct experimental evidence of presence in at least one plant species. In addition, PMN 15 includes 1,167,691 proteins encoding metabolic enzymes and transporters where 3,436 have direct experimental evidence for at least one assigned enzymatic function. There are 9,129 reactions , and 7,316 compounds. Compared to the PMN 10 release described in Schläpfer et al. , PMN 15 increases the number of species 4.7-fold and proteins 8-fold, and adds 2,929 more reactions, 2,178 more compounds, 66 more pathways, and 3,229 more references . Data in the PMN databases are represented using structured ontologies consisting of hierarchical classes to which pathways and compounds are assigned by PMN curators, which makes statistical enrichment analyses possible. The pathway and compound ontology classes, alongside the phylogeny of the included species, illustrate the breadth of metabolic information and species included in the database . Prominent specialized metabolism classes such as terpenoids and phenylpropanoids are highly represented in the databases. This large volume of metabolic information makes PMN a unique resource for plant metabolism. The reference database, PlantCyc, is a comprehensive plant metabolic pathway database. PlantCyc 15.0.1 contains experimentally supported metabolic information from 515 species. Most of the data come from a few model and crop species . For example, Arabidopsis thaliana contributes to 43.4% of experimentally supported enzyme information in PlantCyc, followed by 7.46% from Chlamydomonas reinhardtii and 3.37% from Zea mays. Compared to other metabolic pathway databases such as KEGG and Plant Reactome , PlantCychas substantially higher numbers of experimentally supported reaction and pathway data . PlantCyc 15 includes 3,077 experimentally validated reactions with at least one curated enzyme and 1,163 curated pathways . Plant Reactome includes 1,887 and 320 curated reactions and pathways, with 677 reactions and 266 pathways predicted to occur in A. thaliana , while KEGG includes 543 experimentallysupported pathways as of February, 2021, with 136 occurring in A. thaliana. Data on the number of reactions in KEGG that were experimentally validated were not available at the time of publication. The reference information in PlantCyc is incorporated into MetaCyc, which also includes experimentally supported metabolic information from non-plant organisms and is used to predict species-specific pathway databases . In addition to the reference database PlantCyc, PMN 15 contains 126 organism-specific metabolism databases . These databases range widely in the plant lineage including several green algae and nonvascular plants. The majority of the plants are angiosperms with the Poaceae family most highly represented with 25 organisms. There are also 8 pairs of wild and domesticated plants, including rice, wheat, tomato, switchgrass, millet, rose, cabbage, and banana, alongside their wild relatives . Finally, PMN 15 includes 6 medicinal plants : Camptotheca acuminata, Cannabis sativa, Catharanthus roseus, Ginkgo biloba, Salvia miltiorrhiza, and Senna tora. The newest addition to the list of the medicinal plants is Senna tora, which is a rich source for anthraquinones and whose recent genome sequencing and metabolic complement annotation helped discover the first plant gene encoding a type III polyketide synthase catalyzing the first committed step in anthraquinone biosynthesis . This rich collection of species-specific metabolic pathway databases enables a wide range of analyses and comparisons. To promote interoperability and cross-referencing with other databases, PMN databases contain links to several compound databases such as ChEBI , PubChem , and KNApSAcK . PubChem containins over 270 millionchemical entries as of March 2021, and 95% of PMN compounds link to it. ChEBI release 197 has 58,829 entries and serves as a primary source of compound structural information during curation into PMN databases. Within PMN, 65% of compounds link to ChEBI. Examining 50 randomly chosen compounds that are not mapped to ChEBI suggest that the majority of the remaining 35% compounds do not yet exist in ChEBI . KNApSAcK links are comparatively rare, as only 1.7% of compounds have had a KNApSAcK link added by curators.