Microbiota-based therapy and health promotion focusing on lactate metabolism

Shir-Ly Huang (黃雪莉)*1, Shi-Min Zhang (張世旻)1, Ngoc Yen Tran1,

Jia-He Hung (洪嘉和)2

Institute of Microbiology and Immunology1,

School of Medicine2,
National Yang Ming Chiao Tung University, Taipei, Taiwan

Over the past two decades, the human microbiota were found to have important
roles in health maintenance. Veillonella spp. are obligately anaerobic, Gram-negative
bacteria found in the human oral cavity and gut. They belong to Bacillota and
Veillonellaceae. Recent studies have indicated that gut Veillonella promote human
homeostasis by utilizing lactate as main carbon source and producing beneficial
metabolites. The health promoting metabolites include propionate, acetate,
tryptophan-derivatives and NO2-/NO. The gut lumen is a dynamic environment with
fluctuating nutrient levels, so the microbes exhibit shifting growth rates with
significant gene expression. Current knowledge of Veillonella lactate metabolism has
focused on log phase growth. However, most of the time the gut microbes are in the
stationary phase. The global gene expression was demonstrated that V. dispar
reprograms during growth phases on lactate to explain the metabolites production
during stationary phase. The relationship between mucin-binding probiotics and
Veillonella species were systemically paired and demonstrated some pairs are mutual.
The physical interaction of the two types of bacteria was observed. V. dispar produced
about threefold higher levels of acetate and propionate, in the co-culture with
lactobacilli. Our interbacterial studies, combining traditional and next generation
probiotics, provide a better understanding of human health-promoting mechanism. As
the lactic acidosis causing neural toxicity, inflammation and promoting cancer
metastasis, our cross-feeding lactate-utilizing bacterial strategy can be applied as
potential microbiota-based therapies.