Entry 18
Probiotic science page
Produces lactase to improve lactose digestion and supports gut barrier function as a yogurt starter.
Overview
Streptococcus thermophilus is a Gram-positive, heat-loving lactic acid bacterium. Together with Lactobacillus delbrueckii subsp. bulgaricus, it makes up the classic yogurt starter culture [1]. The complete genome (1.82 Mb) was sequenced in 2004. This gave a foundation for comparing genomes to study dairy adaptation [1]. Two strains are of particular research interest. MN-ZLW-002 has been studied for gut-brain axis effects, bile acid metabolism, and blocking fat cell formation [2–4]. TH-4 has been studied for boosting folate content in fermented foods [5]. S. thermophilus belongs to the genus Streptococcus. It was not affected by the 2020 Lactobacillus reclassification. An ESPGHAN position paper covers the use of probiotics, including S. thermophilus-containing products, in preterm infants [6].
Mechanism
Gut-brain axis (MN-ZLW-002): Both live and heat-killed forms of MN-ZLW-002 improved cognitive problems in APP/PS1 Alzheimer’s model mice. Spatial memory improved most [2]. Live MN-ZLW-002 directly changed the gut microbiome and raised serum IL-1β and IL-6. Heat-killed MN-ZLW-002 raised propionic acid in the colon and boosted antioxidant capacity in the hippocampus [2]. High doses reduced astrogliosis (overgrowth of support cells) in the hippocampus [2]. These findings show that live and heat-killed forms trigger different pathways along the gut-brain axis [2].
Bile acid metabolism (MN-ZLW-002): In mice fed a high-fat diet, oral MN-ZLW-002 raised the relative amounts of Ruminococcaceae, Lachnospiraceae, and Streptococcaceae. It also improved blood glucose, liver cholesterol buildup, and serum IL-10 [3]. The strain tuned the gut microbiome by adjusting the mix of bile acids in the stool. It counteracted the shift toward an obese-type bile acid pattern caused by the high-fat diet [3].
Anti-adipogenesis (MN-ZLW-002): MN-ZLW-002 spurred RAW264.7 macrophages to produce IL-6 and TNF-α. This triggered phosphorylation of p38, p44/42 MAPK (ERK), and NF-κB [4]. Conditioned medium from these macrophage co-cultures blocked 3T3-L1 pre-fat cells from turning into mature fat cells. This shows an indirect anti-fat-cell mechanism through macrophage activation [4]. When heat-killed MN-ZLW-002 was treated with RNase, cytokine production dropped. This suggests that bacterial RNA helps trigger the immune signal [4].
Folate production (TH-4): TH-4 produces folate in fermented soy products. Folate content rises after fermentation [5]. Growing TH-4 together with passion fruit by-product and fructooligosaccharides boosted folate production. But TH-4 viability fell during storage [5].
Health Benefits
Alzheimer’s model (MN-ZLW-002, animal): Live and heat-killed MN-ZLW-002 improved cognitive problems in APP/PS1 mice. The effect came through gut-brain axis changes [2]. (Evidence level: animal model)
Metabolic health (MN-ZLW-002, animal): MN-ZLW-002 improved blood glucose, liver cholesterol, and bile acid makeup in mice fed a high-fat diet [3]. (Evidence level: animal model)
Anti-adipogenesis (MN-ZLW-002, in vitro): MN-ZLW-002 blocked pre-fat cells from maturing. It did this by activating macrophages through MAPK and NF-κB signaling [4]. (Evidence level: in vitro)
Folate bio-enrichment (TH-4, in vitro): TH-4 raised folate content in fermented soy products. Folate bio-accessibility was confirmed under simulated gut conditions [5]. (Evidence level: in vitro)
Preterm infant probiotics (position paper): An ESPGHAN position paper evaluates the evidence for probiotic use in preterm infants. This includes S. thermophilus-containing products [6]. (Evidence level: clinical practice guideline)
> Note: Strain-specific human RCTs for MN-ZLW-002 and TH-4 are not available in the current literature. Evidence is limited to animal models, in vitro studies, and a position paper on probiotic use in preterm infants. Clinical translation requires further investigation.
Biology
Genome: 1.82 Mb. The genome of S. thermophilus LMG 18311 (sequenced by Bolotin et al.) revealed a compact genome adapted to milk. It has limited ability to make its own nutrients and carries a single urease operon [1].
Thermophilic adaptation: Grows best at 37–42°C. It has a cooperative metabolism with L. bulgaricus in yogurt [1].
Gut-brain modulation: Live and heat-killed forms use different mechanisms. Live bacteria change the microbiome and systemic cytokines. Heat-killed bacteria boost short-chain fatty acid production and antioxidant capacity in the central nervous system [2].
Immunostimulatory RNA: Bacterial RNA helps activate macrophages. RNase treatment removed this effect [4].
Taxonomy: S. thermophilus belongs to the genus Streptococcus (family Streptococcaceae). It was not affected by the 2020 reclassification of the genus Lactobacillus.
Bibliography
[1] Bolotin A, et al. (2004). “Complete sequence and comparative genome analysis of the dairy bacterium Streptococcus thermophilus.” Nat Biotechnol. 22(12):1554–8. PMID: 15543133
[2] Zhang Y, et al. (2024). “Live and Heat-Inactivated Streptococcus thermophilus MN-ZLW-002 Mediate the Gut-Brain Axis, Alleviating Cognitive Dysfunction in APP/PS1 Mice.” Nutrients. 16(6). PMID: 38542758
[3] Luo Y, et al. (2022). “Influence of high-fat diet on host animal health via bile acid metabolism and benefits of oral-fed Streptococcus thermophilus MN-ZLW-002.” Exp Anim. 71(4):468–480. PMID: 35793979
[4] Kang X, et al. (2021). “Streptococcus thermophilus MN-ZLW-002 Can Inhibit Pre-adipocyte Differentiation through Macrophage Activation.” Biol Pharm Bull. 44(3):316–324. PMID: 33390424
[5] Albuquerque MAC, Yamacita DS, Bedani R, LeBlanc JG, Saad SMI. (2019). “Influence of passion fruit by-product and fructooligosaccharides on the viability of Streptococcus thermophilus TH-4 and Lactobacillus rhamnosus LGG in folate bio-enriched fermented soy products and their effect on probiotic survival and folate bio-accessibility under in vitro simulated gastrointestinal conditions.” Int J Food Microbiol. 292:126–136. PMID: 30597427
[6] van den Akker CHP, et al. (2020). “Probiotics and Preterm Infants: A Position Paper by the European Society for Paediatric Gastroenterology Hepatology and Nutrition Committee on Nutrition and the European Society for Paediatric Gastroenterology Hepatology and Nutrition Working Group for Probiotics and Prebiotics.” J Pediatr Gastroenterol Nutr. 70(5):664–680. PMID: 32332478
Available Products
S. thermophilus is a component of virtually all commercial yogurt and fermented dairy starter cultures.
MN-ZLW-002 is a research strain from Inner Mongolia Agricultural University. It is under study for functional food uses.
TH-4 is used in research on folate-enriched fermented products.