Live and Heat-Inactivated Streptococcus thermophilus MN-ZLW-002 Mediate the Gut-Brain Axis, Alleviating Cognitive Dysfunction in APP/PS1 Mice.

Research on regulating brain functions with probiotics and postbiotics through the gut-brain axis is attracting attention, offering the possibility of adjuvant therapy for Alzheimer's disease (AD). Three-month-old male APP/PS1 mice were gavaged with live and heat-inactivated S. thermophilus MN-002 for three months. This study demonstrated that live and heat-inactivated S. thermophilus MN-002 improved cognitive dysfunctions in APP/PS1 mice, especially in spatial memory. However, the main effects of live S. thermophilus MN-002 directly altered the intestinal microbiota composition and increased serum IL-1ß and IL-6. Heat-inactivated S. thermophilus MN-002 increased colonic propionic acid levels and enhanced the hippocampus's antioxidant capacity. Furthermore, the changes were more obvious in the high-dose group, such as astrogliosis in the hippocampus. These results indicate that different forms and doses of the same strain, S. thermophilus MN-002, can partly improve cognitive functions in AD model mice via the gut-brain axis.

Bifidobacterium infantis and 2'-fucosyllactose supplementation in early life may have potential long-term benefits on gut microbiota, intestinal development, and immune function in mice.

The health benefits of nutritional interventions targeting the gut microbiota in early life are transient, such as probiotics, prebiotics, and synbiotics. This study sought to determine whether supplementation with Bifidobacterium infantis 79 (B79), 2'-fucosyllactose (2'-FL), or both (B79+2'FL) would lead to persistent health benefits in neonatal BALB/c mice. We found that at postnatal day (PND) 21, Ki67 and MUC2 expression increased, while total serum IgE content decreased in the B79, 2'-FL, and B79+2'-FL groups. The gut microbiota structure and composition altered as well. The levels of propionic acid, sIgA, and IL-10 increased in the 2'-FL group. Moreover, butyric acid content increased, while IL-6, IL-12p40, and tumor necrosis factor-α decreased in the B79+2'-FL group. At PND 56, Ki67 and MUC2 expression increased, whereas the gut microbiota remained altered in all 3 groups. The serum total IgG level increased only in the B79+2'-FL group. In conclusion, our study suggests that early-life supplementation with B79, 2'-FL, or their combination persistently alters the gut microbiome and promotes intestinal development; the immunomodulatory capacity of B79 and 2'-FL occurs during weaning, and their combination may persist into adulthood.

[Heat-inactivated Streptococcus thermophilus MN002 alleviate lipid metabolism of high fat diet-fed induced obese mice through modulating gut microbiota structure and bile acids].

OBJECTIVE: To explore the effects of heat-inactivated Streptococcus thermophilus MN-ZLW-002(MN002) on glucose metabolism, lipid metabolism, gut microbiota and bile acids in high-fat diet fed obese mice. METHODS: Sixty 3-week-old male C57BL/6 mice were randomly divided into control group, high-fat group and intervention group(n=20). After 1 week of adaptive feeding, the control group was fed with normal chow and continued intragastric administration of normal saline for 12 weeks, the high-fat group was fed with high-fat diet and continued intragastric administration of normal saline for 12 weeks, and the intervention group was fed with high-fat diet and continued intragastric of MN002 for 12 weeks. During the experiment, the body weight, food intake, fasting blood glucose content of mice were measured and feces were collected. At the end of the experiment, the oral glucose tolerance of mice was measured and blood, periintestinal fat, peritestosterone fat and perirenal fat samples were collected. The histopathological changes of liver were observed by hematoxylin-eosin staining. Triglyceride, low density lipoprotein, high density lipoprotein and total cholesterol were detected by automatic biochemical analyzer, bile acids content in feces was detected by liquid chromatography-mass spectrometry, gut microbiota structure of mice was analyzed by 16S rDNA sequencing. RESULTS: Compared with high fat group, serum triglyceride, total cholesterol and perirenal fat in intervention group were significantly decreased(P<0.05), the content of fossil cholic acid sulfate in feces was significantly increased, while the content of ursodeoxycholic acid, porcine deoxycholic acid and deoxycholic acid were significantly decreased(P<0.01). Heat inactivation of MN002 could significantly increase the relative abundance of Ruminiclostridium and Alistipes and reduce the relative abundance of Lactobacillus(P<0.01). CONCLUSION: Heat-inactivated Streptococcus thermophilus MN002 can regulate the gut microbiota structure and bile acid composition and content of high-fat diet fed mice, thereby alleviating the lipid metabolic disorders caused by high-fat diet.

Streptococcus thermophilus MN-ZLW-002 Can Inhibit Pre-adipocyte Differentiation through Macrophage Activation.

It is well documented that obesity and metabolic syndrome have a deep association with the intestinal immune system of the host animal. Recent studies indicate that some selected probiotics can modulate the immune responses of the host animal, thereby altering its lipid metabolism. However, the underlying mechanisms are still not fully understood. This study was conducted to investigate the possibility of probiotics to activate macrophages in the hosts, thus alter the differentiation of pre-adipocytes. In this study, Streptococcus thermophilus MN-ZLW-002 (MN-ZLW-002) was co-cultured with RAW264.7 macrophages, with Lactobacillus rhamnosus GG (LGG) as a control. The conditioned medium (CM) of the co-culture was collected and then added to 3T3-L1 pre-adipocytes. Viable and heat-killed (80 °C, 30 min) MN-ZLW-002 stimulated RAW264.7 cells to produce significant amounts of interleukin (IL)-6 and tumor necrosis factor (TNF)-α and induced intense phosphorylation of P38, p44/42 mitogen-activated protein kinase (MAPK) (extracellular signal-regulated kinase (ERK)) and nuclear factor κB (NF-κB). Cytokine production reduced dramatically when heat-killed MN-ZLW-002 was treated with Ribonuclease. Viable and heat-killed LGG induced less cytokine production and little signaling protein activation. Viable and heat-killed MN-ZLW-002-stimulated RAW264.7-CM notably suppressed pre-adipocytes differentiation. However, viable LGG-stimulated RAW264.7-CM had a weaker effect and heat-killed LGG-stimulated RAW264.7-CM had no effect. These findings suggest that viable and heat-killed (80 °C, 30 min) MN-ZLW-002 may alter its lipid metabolism by regulating its immune response, possibly via the release of cytokine, particularly TNF-α. The RNA of heat-killed MN-ZLW-002 may be a key component in its immune activation effect.

Complete Genome Sequence of Lactobacillus acidophilus MN-BM-F01.

Lactobacillus acidophilus MN-BM-F01 was originally isolated from a traditional fermented dairy product in China. The characteristics of this bacterium are its low post-acidification ability and high acid-producing rate. Here, we report the main genome features of L. acidophilus MN-BM-F01.

Complete Genome Sequence of Streptococcus thermophilus MN-BM-A02, a Rare Strain with a High Acid-Producing Rate and Low Post-Acidification Ability.

Streptococcus thermophilus MN-BM-A02 was originally isolated from a traditional fermented dairy product in China. The characteristics of this bacterium are its high acid-producing rate and low post-acidification. This study presents the genome sequence of MN-BM-A02. Its complete genome comprises 2,025 genes and 1,850,434 nucleotides with an average G+C content of 39%.