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Rob Knight and Jing-Yuan Fu Elaborate On Microbiome Research Trends at the 7th Asia Microbiome Conference(AMC)

by Aurora Mau
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The Institute of Biological Chemistry (IBC), Academia Sinica, National Taiwan University Hospital (NTUH), and BIOTOOLS hosted the 7th annual Asia Microbiome Conference (AMC) on January 7th, 2023, at Academia Sinica, Taiwan. With over 400 hundred domestic and foreign microbiome experts participating in this grand event, it fully demonstrates Taiwan’s rich microbiology research capabilities. Also, it shows the international trend of attaching importance to microorganisms as biological therapeutic products or cross-species microbial diversity research.

the 7th annual Asia Microbiome Conference
The 7th Asia Microbiome Conference (AMC)

Professor Knight’s Microbiome Research with Big Data

Professor Rob Knight from the University of California San Diego (UCSD) gave the Keynote speech, “Scaling microbiome studies to address global problems.” As a co-founder of multiple significant microbiome research programs, including the Earth Microbiome Project and American Gut Project, Professor Knight first elaborated on the relationship between the microbiome and human health. Even though more than 99% of human genes are from microbiomes, the importance of microbiomes is often neglected. To increase the speed of analyzing microbiome data, professor Knight’s lab has successfully developed Qiita, allowing researchers to perform microbiome multi-omics comparisons, accelerating the accumulation of microbiome data.

the 7th annual Asia Microbiome Conference, Professor Rob Knight from the University of California San Diego (UCSD)
Professor Rob Knight from the University of California San Diego (UCSD)

Professor Knight also shared the lab’s effort to analyze genomics in wastewater on the UCSD campus during the COVID-19 pandemic. Not only could they detect at least 85% of COVID-19 cases, but they could also discover the COVID-19 virus variants beforehand, allowing the surrounding society to control the pandemic better. 

With the explosive growth of total genome data (also known as metagenomics) from the natural environment, professor Knight joined the Greengene research project to improve sequencing accuracy. With full-length 16S rRNA sequencing and shotgun metagenomic Taxonomic, they can establish a more accurate classification standard for microbiomes.

In addition, professor Knight pointed out that, so far, advanced countries dominate the majority of microbiome research. Therefore, breaking the geographical limitations of microbiome research is necessary to expand the scope of genetic databases and applications.

Microbiome Translation Study in Colorectal Cancer

Following up, professor Jun Yu from the Chinese University of Hong Kong talked about the relationship between microbiome and cancer, particularly in colorectal cancer (CRC).

An accumulation of research papers demonstrates certain microbiome roles in the oncologic mechanism of CRC, including the animal model’s gut microbiota malfunction caused by P. anaerobius, and Fusobacterium nucleatum’s regulation on the expression of E-cadherin protein, leading to the increased risk of tumor proliferation and metastasis. Furthermore, research has shown that smoking increases the risk of having CRC by affecting the gut microbiome and its metabolism.

Professor Jun Yu from the Chinese University of Hong Kong
Professor Jun Yu from the Chinese University of Hong Kong

Professor Yu then talked about how the microbiome could act as another treatment strategy to improve the efficacy of cancer immunotherapy, demonstrating the potential of personalized microbiome therapy in treating cancer. It is known that some microbial species would lead to bad outcomes of immunotherapy in treating melanoma. However, combining fecal microbiota transplantation (FMT) with immunotherapy can increase the response of CD8+ T cells, along with the efficacy of anti-PD1 treatment, thus lowering the risk of tumor recurrence. Apart from that, probiotics z also showed its anti-tumor function in CRC by increasing the immune regulation of IFN-γ.

Additionally, microbiota composition also plays a key role in the efficacy of some common drugs. When treating patients with Lysinibacillus sphaericus, Professor Yu pointed out that physicians should be cautious with the Asprin dosage since Lysinibacillus sphaericus affects the chemopreventive in Asprin.

Professor Yu further mentioned that a non-invasive microbial biomarker test is perfect for early cancer diagnosis. The M3CRC test kit, developed by the Chinese University of Hong Kong, is now available in Hong Kong and other countries.

Related Article: Leveraging Synthetic Biology, Microbiome-based Therapies Open Up Possibilities for Clinical Applications

Addressing Unmet Medical Needs for NASH with Microbiome Therapy

The treatment options for nonalcoholic steatohepatitis, also known as NASH, often involve diet control, lifestyle modification, and weight loss surgery. However, with no medical treatment approved by the U.S. FDA, the unmet medical needs for NASH are still massive.

Dr. Ming-Shiang Wu, the dean of the National Taiwan University Hospital
Dr. Ming-Shiang Wu, the dean of the National Taiwan University Hospital

Dr. Ming-Shiang Wu, the National Taiwan University Hospital dean, shared how microbiome research has brought new insights into NASH treatment. By treating animal models with FMT after weight loss surgery, the gut microbiota could help to lower glycogen and lipid concentrations. Dr. Wu also shared some examples of probiotic species, including Akkermansia muciniphila, Odoribacter splanchnicus, along with some harmful microbiomes that are known to accelerate the progression of NASH, such as Catenibacterium mitsuokai and Ruminococcus torques

When combining microbiome treatment with NASH nutrition therapy or exercise, the chemical LT-17, extracted from ginger oil or fermented soybeans, has been demonstrated to regulate liver metabolism. The clinical trial of LT-17 is currently ongoing. In addition, combining FMT with aerobic exercise also showed positive results in improving NASH.

The 7th Asia Microbiome Conference (AMC)
From left to right, Dr. Ming-Shiang Wu, Prof. Rob Knight, Prof. Jun Yu, and Hsin-Chih Lai from Chang Gung University

At the end of the morning session, three speakers joined the panel discussion. Professor Yu first shared how she started researching the relationship between microbiome and cancer; professor Knight then talked about the importance of building a microbiome database. Dr. Wu shared his experience treating NASH patients as a physician and how he improved the patients’ disease progression by finding a breakthrough in diet control and lifestyle modification.

Microbiome Research in Human and Non-human Studies

At the microbiome in the human study session, Dr. Yao-Jong Yang addressed the gut-skin axis and the relationship between infants’ gut microbiota imbalance and skin diseases, particularly atopic dermatitis. Dr. Yang pointed out that early-life gut microbiota dysbiosis with a decrease of Lactobacillus at week four and Bifidobacterium at week 16 may serve as a biomarker to predict the occurrence of infantile colic and atopic dermatitis in infants, respectively. 

Professor Hsueh-Fen Juan from National Taiwan University introduced the study regarding small-RNA sequencing on the gut microbiome. Aside from the previous method to identify bacteria expression profiles, such as RNA-seq and whole genome sequencing (WGS), professor Juan’s research team evaluated bacterial abundance in 32 types of cancer by using The Cancer Genome Atlas (TCGA) miRNA sequencing data, complementing previously published databases. 

Professor Wei-Kai Wu further addressed the research on gut microbiota and its link with chronic metabolic diseases, including type II diabetes, cardiovascular disease (CVD), non-alcoholic fatty liver disease, and sarcopenia. Professor Wu’s research suggests that the oral carnitine challenge test (OCCT) may be used to provide personalized dietary recommendations.

Dr. Wei-Kai Wu from National Taiwan University Hospital and Dr. Yao-Jong Yang from National Cheng Kung University Hospital
Dr. Wei-Kai Wu from National Taiwan University Hospital and Dr. Yao-Jong Yang from National Cheng Kung University Hospital

At the microbiome in the non-human study session, professor Chieh-Chen Huang from National Chung Hsing University introduced his lab’s effort to discover the mechanism of the reverse TCA cycle since it may form at the beginning of the biological metabolism network. Professor Huang shared that his lab’s finding demonstrated the possibility of KOR  (alfa-ketoglutarate oxidoreductase), the key enzyme from reverse TCA machinery, harboring E. coli could act as a cell factory for the extraterrestrial colonization that could produce organic compounds. 

Professor Chih-Hao Hsieh from National Taiwan University shared his research team’s work in developing a novel method, “multiview distance regularized S-map” (MDR S-map), to construct time-varying interaction networks using the series observation data alone. Professor Hsieh pointed out that this new method can help identify important species from the interaction network and reveal mechanisms governing the dynamic stability of a bacterial community.

At the end of the non-human study session, professor Isheng Jason Tsai from Academia Sinica talked about the ecological genomics of Saccharomyces cerevisiae. Taiwan is part of this yeast’s geographic birthplace, where the most divergent natural lineage was discovered. With a WGS of 121 isolates, his research team found nine distinct yeast lineages diverged from Asian lineages during the Pleistocene. Professor Tsai concluded that S. cerevisiae has rich natural diversity sheltered from human influences, making it a powerful model system in microbial ecology.

Isheng Jason Tsai from Academia Sinica, Professor Chih-Hao Hsieh from National Taiwan University, and professor Chieh-Chen Huang from National Chung Hsing University
Isheng Jason Tsai from Academia Sinica, Professor Chih-Hao Hsieh from National Taiwan University, and professor Chieh-Chen Huang from National Chung Hsing University

Related Article: GeneOnline’s Pick: Top 10 New FDA-approved Drugs in 2022

Decoding Microbial Variation in Human Health

At the end of the AMC, professor Jing-Yuan Fu from University Medical Centre Groningen in the Netherlands introduced the results accumulated in 20 years from the biggest microbiome biobank research program worldwide, the LifeLines cohort study.

the 7th annual Asia Microbiome Conference, Professor Jing-Yuan Fu from University Medical Centre Groningen, the Netherlands
Professor Jing-Yuan Fu from University Medical Centre Groningen, the Netherlands

Starting in 2006, researchers from the LifeLines program have studied microbiota in over 160,000 European people for nearly 20 years. By collecting subjects’ blood, feces, and DNA samples and performing multi-omics analysis on the microbiota, the program has accumulated over 2,000 phenotypes of genetic data. Professor Fu pointed out that researchers can characterize the genetic landscape of the gut microbiome from LifeLines databases, including microbial structural variations (SVs), single nucleotide polymorphisms (SNPs), and the presence and absence of genes. Besides, financial status and environmental exposure factors also play crucial roles in individuals’ gut microbiota composition.

Professor Fu concluded that, when it comes to the effect of microbial variation on human health, researchers should include all the factors, including species, genetic variation, environmental exposures, and especially the genetic variation in microbiota. Therefore, we can get a whole picture of how microbial affect human health.

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