I am deeply grateful to Professor Cheng-Yen Kao from the Institute of Microbiology and Immunology at National Yang Ming Chiao Tung University. Five years ago, I reached out to him via email to express my strong interest in conducting probiotic-related research in his lab. He kindly agreed to an interview and soon after welcomed me into his laboratory to carry out experimental work for science competitions.
During my time there, I had the opportunity to participate in a variety of microbiology-related experiments and projects, including a three-year large-scale industry-academic collaboration focused on microbial strain development, as well as a study on probiotic alternatives to antibiotics in treating vaginal infections.
After three years of experimental training, Professor Kao approved my participation in a graduate research team working on the related researches of next-generation probiotics isolated from the human body. I collaborated with PhD students on a series of functional and characterization experiments, and I also contributed to the writing of related academic papers.
The human gut microbiome is integral to digestion, overall health, and metabolic disorder imbalances. Recent advancements in fecal microbiota transplantation (FMT) have highlighted the therapeutic promise of restoring healthy gut microbiota in populations with high incidences of diseases.
Focusing on fecal DNA samples from healthy Asian individuals, this study examines the potential of novel Akkermansia strains, specifically Akkermansia muciniphila (Z62) and Akkermansia massiliensis (IR119), as next-generation probiotics for mitigating metabolic syndrome.
The investigation of short-chain fatty acids (SCFAs), which are produced and play a crucial role in regulating metabolic processes. SCFAs such as butyrate, acetate, and propionate are essential for energy provision to colon cells and exerting anti-inflammatory effects.
The methodology involves selecting two Akkermansia strains, analyzing them through 16S rRNA and WGS, evaluating their growth and survival rates under acidic and bile-salt conditions, alongside their cell adhesion capabilities.
The study focuses on the production of key short-chain fatty acids (SCFAs) and tryptophan derivatives by bacteria in regulating metabolic processes, as well as their anti-inflammatory effects on colon cells.
Through in vitro assays, both strains exhibited survival in acidic/bile-rich conditions, though Z62 demonstrated superior adhesion to Caco-2 cells, suggesting a higher colonization potential. Metabolomic analysis revealed both strains produce SCFAs, including propionic and acetic acids, and indole metabolites, such as indole-3-propionic acid and indole-3-acetic acid, which are known to influence lipid metabolism and insulin sensitivity. In adipocyte cell models, IR119 significantly reduced lipid accumulation, while Z62 increased lipid presence. Furthermore, IR119 reduced pro- inflammatory cytokine levels, including IL-6 and TNF-α, suggesting potential for inflammation mitigation.
The future potential of IR119 as a therapeutic probiotic is extraordinary in addressing complex metabolic and inflammatory diseases, which open new avenues for managing chronic inflammatory conditions like type 2 diabetes and cardiovascular disease. Future clinical trials could refine IR119’s efficacy, positioning it as a leading probiotic in preventive and therapeutic contexts.
Next-generation probiotics (NGPs), also known as second-generation probiotics, refer to newly identified, scientifically engineered, or clinically targeted strains of microbes that go beyond traditional probiotic species like Lactobacillus and Bifidobacterium. These strains are selected or modified for specific therapeutic purposes and are often part of the human gut microbiome, but have not been traditionally used in food or supplements.
I conducted microbiological research investigating the role of novel Akkermansia massiliensis strains in regulating lipid metabolism via secretion of short-chain fatty acids (SCFAs), aiming to develop next-generation probiotics that contribute to metabolic health sustainability.
Often isolated from healthy human microbiota (not dairy or fermented foods)
Designed to address specific diseases or metabolic pathways
Supported by metagenomic, metabolomic, and clinical research
Some are being developed as Live Biotherapeutic Products (LBPs) for FDA approval
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| Strain | Source | Key Function |
|---|---|---|
| Akkermansia muciniphila | Human gut mucosa | Improves gut barrier, regulates metabolism, linked to obesity and diabetes prevention |
| Faecalibacterium prausnitzii | Human colon | Strong anti-inflammatory effects, reduced in IBD patients |
| Clostridium butyricum | Soil and gut | Produces butyrate, supports immune balance, used in Asia |
| Bacteroides fragilis (non-toxigenic) | Gut | Immune regulation via polysaccharide A, used in preclinical cancer models |
| Eubacterium hallii | Gut | Converts lactate to butyrate, supports energy balance |