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 the host generally cannot absorb from the diet [273]. Microbes such as B. thetaiotaomicron have been shown to induce the expression of monosaccharide transporters in mice [274], where the polysaccharides are hydrolyzed into monosaccharides and SCFAs for easy absorption by the host intestinal cells. The increase of sugar uptake is then converted to lipids in the liver, triggering intestinal microbes to facilitate host expression fat metabolism gene Fiaf resulting in the accumulation of excessive fat [275]. Other studies have shown that orally introduced probiotics in mice fed with a high‐fat diet prevent the perturbation of intestinal mucosal permeability and limit energy absorption. These oral probiotics exert such bioactivity by reducing plasma LPS and cytokines and promote the gut secretion of glucagon‐like peptide‐1 (GLP‐1) and glucagon‐like peptide‐2 (GLP‐2) involved in maintaining the intestinal mucosal barrier [276].
1.3.5.2 Diabetes
Diabetes is a metabolic disorder that results in an increased sugar serum level, often resulting from the deficiency of insulin secretion or insulin insensitivity. Studies have shown that bacterial abundance in the gut has a strong correlation to the onset of diabetes. This has been shown in type II diabetes (T2D) patients that showed increased Firmicutes abundances with a proportional decrease in Bacteroidetes abundance. Long‐term observation of T2D patients undergoing weight loss showed a recovery of Bacteroidetes abundance and depletion of Firmicutes population [131]. It was discovered that the ratio of GI Firmicutes/Bacteroides affects the body metabolism, where patients with higher ratio were shown to be more susceptible to inflammatory responses, increased BMI, and a higher risk of developing insulin resistance that may lead to type 2 diabetes [271, 275, 277]. Certain studies indicated that orally administered prebiotics helps lower the ratio in hyperphagic, obese, and hyperglycemic mice model (ob/ob), which caused an increase in the number of L‐cells [278]. The increase of L‐cells raises the plasma levels of GLP‐1, triggering glucagon expression, resulting in leaner mice compared to the untreated groups.
1.3.5.3