Principles in Microbiome Engineering. Группа авторов

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 as the integrated HMP (iHMP), uses the Data Analysis and Coordination Center (DACC) platform to facilitate rapid data retrieval of metagenomic sequence and other data types of the human microbiome and human genetics.

       METAgenomics of the Human Intestinal Tract (MetaHIT): MetaHIT (2008–2012) is a European Union initiative that links 15 institutes from 8 countries, providing a multi‐disciplinary and extensive catalogue of microbiome resilience potential in the human body [287]. MetaHIT was succeeded by the Horizon2020 (2014–2020) that advances research in microbiome nutrition and host health.

       The Microsetta Initiative (TMI): TMI consolidates the global efforts of profiling the microbiome of collected human samples from across the globe, including educational outreach of microbiome sciences [288]. TMI is the human microbiome research wing of the Earth Microbiome Project.

       Million Microbiome of Humans Project (MMHP): Launched at the 14th International Conference on Genomics (ICG‐14) in 2019 [289], the MMHP is global cooperation between scientists from China, Sweden, Denmark, France, Latvia, and other countries studying microbial metagenomics research. This project aims to sequence and profiles the microbiome of one million samples isolated from the human body, to ultimately construct a complete human body microbiome map and build the world's largest human microbiome database using MGI's DNBSEQ™ metagenomic sequencing [290].

       Bioinformatic initiatives: The most prominent bioinformatic initiative is the DACC [291] that plays a crucial role in iHMP. The Global Catalogue of Metagenomics (gcMeta) is another bioinformatics platform that archives microbiome data while facilitating data standardization and analysis [55].

      Various governments and their affiliated health institutes have initiated many national‐level microbiome projects to encourage microbiome research. In Ireland, the government‐funded Metagenomics of the Elderly programme (ElderMet) investigates the relationship between diet, gut bacteria, and health status in the elderly [292]. The Canadian Institutes of Health Research (CIHR) launched the Canadian Microbiome Initiative (CMI) in 2014 aiming to analyze and characterize the microorganisms that colonize the human body in an effort to harness the microbiome for treatment of chronic disease [293]. In 2017, the second phase of CMI was launched, aiming to develop effective preventative and therapeutic interventions through