[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 Non‐alcoholic Fatty Liver Disease (NAFLD)
NAFLD is a metabolic disorder that results from the build‐up of liver fat in patients without a history of impaired liver function from heavy drinking, viral infections, or other liver diseases [279, 280]. NAFLD is the most common liver disease globally, with the number of patients increasing annually. Studies have found that the prevalence of NAFLD is linked to gut microbiota, where patients with liver failure often observe microbial overgrowth of small intestinal and are used as an indicator to determine the liver failure severity [281]. As discussed earlier, the ratio of Firmicutes/Bacteroides affects the host insulin resistance. On top of that, the ratio affects increasing endogenous ethanol production and inducing choline deficiency in the host increasing the risk of NAFLD development [282]. Ethanol produced by the microbiota increases intestinal mucosal permeability that coupled with choline deficiency, triggers the toll‐like receptors, which stimulate hepatocytes to produce plentiful cytokines involved in NAFLD pathogenesis [283].
Prebiotics and lactulose are commonly used to treat NAFLD enriching the Bifidobacterium abundance. Other prebiotics from the inulin‐type fructose fed to NAFLD animal models were shown to reduce the development of hepatic steatosis. These oligofructoses reduce fatty acid synthesis, promote weight loss by regulating intestinal polypeptides, reducing inflammation and proinflammatory cytokines, improving blood sugar regulation, and regulating intestinal microbiota [281, 284].
1.4 Challenges and Opportunities
1.4.1 Limitations in the Field
While we have observed great strides in microbiome research, there are many more aspects that would need further investigation. Currently, most studies focus on the effects of the single nutrient and its role in modulating microbiota. However, human dietary habits are complex, where synergistic effects of nutrients might need to be further investigated. Further, a larger cohort of long‐term human microbiome studies would be needed to map and predict the shift in the microbiome. This would include the role of dietary and socio‐economic impacts on the human host [96]. Additionally, further studies linking diet and daily activities would be needed. Studies suggest higher gut Shannon index in individuals who regularly exercise and practice good dietary habits compared to sedentary individuals [285]. Thus, further research would be merited to understand better the role of microbiome, diet, and human health.
1.4.2 Current Microbiome Project Supporting Infrastructures
The US NIH initiated the research on the human microbiome that triggered a global effort in this field. In 2008, the International Human Microbiome Consortium (IHMC) was established to set up globally accepted policies and coordinate international microbiome initiatives, including those in the EU, US, China, Japan, Singapore, Australia, and Canada. Table 1.5 shows the current supporting agencies in different countries.
Table 1.5 Infrastructures supporting microbiome research.
| Countries | Supporting agencies |
|---|---|
| Australia | Commonwealth Scientific, Industrial Research Organisation, National Health and Medical Research Council |
| Canada | Canadian Institutes of Health Research, Genome Canada |
| Europe | European Commission |
| France | Institut National de la Recherche Agronomique |
| Gambia | Medical Research Council |
| Germany | European Molecular Biology Laboratory |
| Ireland | Teagasc Moorepark Food Research Centre, University College Cork |
| Japan | Japan Science & Technology Agency, JST, Ministry of Education, Cultures, Sports, Sciences and Technology, MEXT |
| Kazakhstan | Nazarbayev University |
| Korea | National Research Foundation, Korea Research Institute of Bioscience and Biotechnology (KRIBB) |
| United States of America | National Institutes of Health (NIH) |
| China | Institute of Microbiology, Chinese Academy of Sciences |
1.4.2.1 International and Local Initiatives
The established infrastructures kickstarted various local and global initiatives to accelerate microbiome research. These include databases and research platforms founded by universities, research institutions, and major corporations. These initiatives study diverse research work, focusing on particular human societal niches. Listed below are some of such initiatives.
HMP [286]: The first‐phase HMP (HMP‐1) (2008–2013) is a concerted global effort that investigates samples of donors and studying the microbiome of 15–18 sites of the human body. These microbial taxonomic profiles and metagenomic sequences, described in the form of abundance, lay the foundations for the HMP‐2.
HMP‐2: The second phase of the HMP, also known
