population and providing the substance for microbial fermentation [215–218]. The two most abundant butyrate‐producing Firmicutes in the human colon are E. rectale/Roseburia spp. and F. prausnitzii. E. rectale/Roseburia spp. belongs to the Clostridium coccoides (or Clostridial cluster XIVa) cluster, and F. prausnitzii belongs to the C. leptum (or Clostridial cluster IV) cluster [219–222].
The SCFA butyrate can prevent gut tissue inflammation and suppress cancer cell motility by deactivating Akt/ERK signaling pathway of histone deacetylase in colorectal cancer and lymphoma cancer [223]. Butyrate also exerts its anticancer activity by interfering with the mitochondrial and exogenous apoptotic pathways through regulating oncogenic signaling molecules through microRNAs and methylation [224, 225]. On top of generating butyrate, these bacteria can produce other metabolites such as lactic acid and formic acid that can further exert anticancer activities [226].
Cruciferous plant–rich diet was also found to help in the prevention of colorectal cancer. Cruciferous vegetables are enriched with glucosinolates, a precursor to the anticancer agent isothiocyanates. These glucosinolates require to be catalyzed by the enzyme myrosinase to form its isothiocyanate derivatives. A study showed that cruciferous‐rich and fruit‐rich diet enriches certain groups of Actinobacteria, Firmicutes, and Bacteroides that have weak myrosinase‐like properties [227]. Other approaches to augment the myrosinase activity were achieved using engineered microbes such as E. coli Nissle 1917 [228]. Other means of dietary regulation also reduce the risk of developing cancer by the displacement of pathogens associated with cancer pathogenesis. Colon cancer patients were found to have an enriched population of Fusobacterium nucleatum compared to healthy test subjects detected in both colorectal biopsies and patient stool samples [229–233]. F. nucleatum from the phyla Fusobacteria is a Gram‐negative non‐spore‐forming bacilli that is strictly anaerobic and is usually found in the mouth, playing a role in various diseases such as periodontitis, appendicitis, gingivitis and invasive infections in the other organs. Studies showed that F. nucleatum exerts the cancer pathogenesis through the interaction of three biomolecules located on the surface of the microbe: lipopolysaccharide (LPS), adhesin A (FadA), and fusobacterium autotransporter protein 2 (Fap2) [234]. Fiber‐enriched and low‐fat diet can reduce the risk of F. nucleatum‐positive colorectal cancer through the displacement of the pathogen from the gut; however, the dietary change does not show any significant improvements in F. nucleatum‐negative cancer patients [235]. These studies suggest the role of diet pattern in displacing F. nucleatum, thus negating the risk of colorectal cancer development, showing the relationship between diet, microbiome, and cancer pathogenesis.
1.3.4 Psychological Disease
Increasing studies on the brain–gut–microbiome (BGM) axis describe the bidirectional interactions between the central nervous system, gastrointestinal tract, and gut microbiota [236, 237]. Increasing evidence has proposed that this axis contributes largely to pathologies of some psychological diseases, such as autism spectrum disorder (ASD) [237, 238], Parkinson's disease (PD), and Alzheimer's disease (AD) [239, 240]. This section will discuss the dietary effects on ASD and neurodegenerative diseases.
1.3.4.1 Autism Spectrum Disorder
ASD is a neurodevelopment disorder that influences the social behavior and communication of afflicted individuals throughout their lifetime [241, 242], where ASD severity is linked to the intestinal microbiota and gastrointestinal symptoms [238, 243]. Studies on isolated fecal bacteria from ASD patients revealed microbial dysbiosis resulting in the enrichment of Clostridium, Lactobacillus, and Desulfovibrio species; and decreased Bacteroidetes/Firmicutes ratio [244–247]. Carbohydrate‐degrading bacteria from the Prevotella, Coprococcus, and unclassified Veillonellaceae genera showed lower abundance than healthy people [248]. Despite this observation, the fluctuations of specific bacterial species from different studies are inconsistent, thus proving a challenge to determine the role of bacteria dysbiosis in the pathogenesis of ASD [238]. Clinical research using specialized diet to alleviate ASD symptoms has been studied to perturb these microbiota populations. Gluten‐ and casein‐free (GFCF) diet is currently widely prescribed to children with ASD, designed to reduce leaky gut‐causing proteins and facilitate symptom remission [249]. However, there are some inconsistencies in treatment in some small clinical trials [250–252]. Alternatively, the ketogenic diet was found to improve ASD symptoms both in an animal model and small‐sized clinical experiment despite potentially causing ketosis. This is due to the ketogenic diet to compensate the lower Firmicutes to Bacteroidetes ratio and increase A. muciniphila in mice of ASD [253]. While showing much success in mice, the detailed mechanism linking in a ketogenic diet, gut microbiota, and ASD remains unclear due to the lack of appropriate animal models that mimics the human BGM [254]. In addition to altering dietary composition, probiotics, such as Lactobacillus and Bifidobacterium, have been found to improve ASD behavior while treating the ASD‐linked gastrointestinal symptoms [255, 256].
1.3.4.2 Neurodegenerative Diseases
Neurodegenerative diseases such as Parkinson's disease (PD) and Alzheimer's disease (AD) were found to be exacerbated by the disruption in gut microbiota, contributing to the pathogenesis of neurodegenerative disorders via the BGM [239, 257]. PD patients were reported to observe an increase in genus Lactobacillus, Bifidobacterium, and Akkermansia (pro‐inflammatory, mucin‐degrading Gram‐negative bacteria) population, and a decrease in the Faecalibacterium, Coprococcus, Blautia, Prevotella, and other microbes of the Prevotellaceae family (the bacteria responsible to SCFA production) [258, 259]. Dietary supplementation of specific probiotics, such as Lactobacillus and Bifidobacterium, was found to treat neurodegenerative symptoms in clinical trials and mice [260–262]. Phytochemicals, such as caffeine from ingested coffee and tea, were found to have an inverse relation, lowering the risk of developing PD. [263] It was also shown that caffeine confers neuroprotective properties in PD‐induced mice models [264, 265]. Similar to ASD, a ketogenic diet was identified to improve symptoms of PD and AD both in animal models and clinical trials [266–270]. These results indicate the role of diet in regulating the microbiota population involved in preventing neurodegenerative disease.
1.3.5 Metabolic Disorder
Metabolic disorders are caused by the dysbiosis of intestinal microbiota, resulting in changes in the host's ability to digest certain types of foods. This leads to various disease metabolic disorders such as obesity, diabetes, and non‐alcoholic fatty liver disease (NAFLD). In this chapter, we will discuss these metabolic disorders and their link to diet and the microbiome.
1.3.5.1 Obesity
The gut microbiota composition affects the host's ability to digest different types of food, thereby causing the host to metabolize the nutrients from the food itself. In 2004, a group determined that the gut microbiota regulates lipid storage in the human body [271]. Later in 2006, they found significant differences between the relative abundance of Bacteroidetes and Firmicutes in the GI tract of obese and lean mice. The study also reported that FMT of samples from obese mice to germ‐free mice resulted in the development of obesity pre‐symptoms [131]. The same research group further studied the GI microbiota from monozygotic and dizygotic twins with different weight groups (lean and obese) and discovered large variations in the gut microbiota despite having similar genetic makeup [45]. The research team then conducted FMT of microbiota from the identical twins into germ‐free mice. Groups provided with FMT from lean donors maintained normal weight, while groups treated with FMT from obese donors gained a significant amount of weight throughout the study [272].
The role of gut microbes in regulating fat storage in their human host is mainly attributed to the ability of these microbes to ferment complex polysaccharides that
