Science: Specific Enterococcus How to enhance cancer immunotherapy?
Science——[47.728]
① Specific Enterococcus bacteria (such as Enterococcus faecium) can improve the response of tumor mice to anti-PD-L1 immune checkpoint inhibitor (ICI) treatment; ② these Enterococcus expresses and secretes the homologue of the peptidoglycan hydrolase SagA, which can reconstruct the peptidoglycan component of the bacterial cell wall to generate immunologically active cell wall peptides (such as muramyl dipeptide MDP), thereby passing Activate NOD2 signal to enhance the effect of immunotherapy; ③ Orally supplement model mice with engineered bacteria expressing SagA (such as , Enterococcus faecalis , and probiotics expressing SagA) or injection of synthetic MDP. Enhance the anti-tumor efficacy of ICI (including anti-CTLA-4).
[Editor-in-chief's comment]
Intestinal flora can affect the effect of PD-L1 immunotherapy for cancer patients, but the relevant mechanisms have yet to be explored. A study recently published by Science found that some Enterococcus bacteria can enhance the efficacy of anti-PD-L1 immunotherapy on model mice. Mechanistically, these enterococci can secrete an enzyme called SagA, which can degrade the peptidoglycan component of the bacterial wall, thereby releasing cell wall peptide fragments that can activate the pattern recognition receptor NOD2, and improve the immunotherapy response. Researchers believe that bacterial peptidoglycan remodeling and the production of immunologically active small molecules may be a type of mechanism to enhance the efficacy of immunotherapy, or have broad clinical application prospects in cancer immunotherapy and prognosis prediction. (@Mildbreeze)
[Original information]
Enterococcus peptidoglycan remodeling promotes checkpoint inhibitor cancer immunotherapy
2021-08-27, doi: 10.1126/science.abc9113
How does science affect maternal intestinal infection during pregnancy
Immunity?
Science——[47.728]
① Transient infection of pregnant mice with Yersinia pseudotuberculosis (YopM),The offspring of mice showed an increase in the number of intestinal-specific Th17 cells and increased responsiveness to the flora; ② This long-term effect on the offspring’s intestinal immunity does not depend on the maternal flora, but by pro-inflammatory cytokines IL-6 is mediated in utero: infection increases maternal IL-6, IL-6 acts on fetal intestinal epithelial stem cells, increases their chromatin openness and changes downstream cell functions (such as increasing antigen presentation molecules and antimicrobial peptides) expression); ③ The pregnant mice are infected with YopM or injected with IL-6, so that their offspring are more resistant to intestinal pathogen infection, but at the same time they are also more susceptible to intestinal inflammation.
[Editor-in-Chief's comment]
Most infections that occur during pregnancy are mild and short-lived, but it is still unclear whether this infection will have a long-term impact on the immune system of offspring. A new study published by Science shows that infections from the mother during pregnancy can have a continuous tissue-specific effect on the immune function of the offspring. The study found that the transient infection of pregnant mice with common food-borne pathogens can cause the level of the pro-inflammatory cytokine IL-6 to increase. IL-6 can directly act on the fetal rat intestinal epithelial stem cells in the uterus to change its epigenetic memory, thereby causing a lasting impact on the intestinal immune homeostasis of the offspring. These findings reveal a new mechanism by which maternal microbial exposure affects the immune development of offspring and are recommended for professional reference. (@Mildbreeze)
[Original information]
Prenatal maternal infection promotes tissue-specific immunity and inflammation in offspring
2021-08-27, doi: 10.1126/science.abf3002
: Wang Jinfeng+Zhao Fangqing The intestinal type and evolution pattern of the tract flora
Genome Biology——[13.583]
① Analyze 13,776 fecal flora of 1956 infants from 17 countries in the first 3 years of age,It is found that there are 4 intestinal types, which are led by Firmicutes, Bifidobacterium, Bacteroides and Prevotella respectively; ② Firmicutes and Bifidobacterium enterotypes correspond to the early stage In the development stage, the community structure is relatively unstable and the maturity of the flora is low, while the intestinal types of Bacteroides and Prevotella correspond to the later stages, with high diversity of the flora and stronger relationships within the community; ③ Ecological model and function The analysis shows that the pattern of bacterial population transition from infant to adult is definite and predictable. Firmicutes and bifidobacteria enterotypes are replaced by Bacteroides and Pretotella enterotypes as they grow, accompanied by changes in metabolic pathways.
[Editor-in-Chief's comment]
The intestinal flora in the early life evolves and matures with the growth and development of the baby, and generally stabilizes at the age of 3 and becomes like an adult. Genome Biology recently published the research results of Wang Jinfeng, Zhao Fangqing and their team from the Beijing Institute of Biological Sciences, Chinese Academy of Sciences. Through a large-scale in-depth analysis of the data of nearly 14,000 intestinal flora of nearly 2,000 babies around the world, it revealed the baby’s intestinal type. The law of division and its transformation has important reference value for studying the development pattern of intestinal flora in the early life. (@Mildbreeze)
[Original information]
Deterministic transition of enterotypes shapes the infant gut microbiome at an early age
2021-08-24, doi: 10.1186/s13059-021-02463-3 _p2h1
h19hr h19hr The tract flora may determine the food preference of mice
Gut Microbes——[10.245]
① Transplant the fecal flora of lean mice and diet-induced obese mice into recipient mice; ② Donor mice Take a food preference test,Obese people consume 58% less HFHS (high-fat, high-sugar, delicious food) than lean people; ③The intestinal flora derived from obese mice reduces the intake of HFHS by recipient mice by 40%, that is, the pleasure caused by eating during obesity Reduction can be transferred by transplantation of intestinal flora; ④ This effect is related to the expression of striatal dopaminergic markers, and HFHS intake and Parabacteroides have a high degree of positive correlation; ⑤ Use of broad-spectrum antibiotics to deplete intestinal bacteria Group, will change the intake of HFHS in lean mice.
[Editor-in-chief's comment]
During obesity, the hypothalamus's regulation of food intake changes, and dopamine , which produces a pleasure response to food intake, is also affected. The intestinal flora is also a key factor affecting obesity, whether there is a relationship between the two remains to be further studied. A recent article published by Gut Microbes found that in the food preference test, obese mice had a reduced intake of delicious foods and decreased pleasure, and this decreased pleasure caused by eating can be transferred through intestinal flora transplantation. (@爱的择选)
[Original information]
Gut microbes participate in food preference alterations during obesity
2021-08-23, doi: 10.1080/19490976.2021.1959242
Nature of Shenzhen University: Intermittent Fasting + ERK inhibitors may enhance cancer chemotherapy
Nature Communications——[14.919]
① Knockdown of SIRT7 significantly weakens the anti-tumor efficacy of intermittent fasting IF; ② AMPK leads to phosphorylation of SIRT7, which in turn induces phosphorylation of GSK3β,And stabilize SIRT7 by decoupling E3 ligase UBR5; ③ SIRT7 hyperphosphorylation destroys SKP2-SCF E3 ligase, prevents SKP2-mediated AKT polyubiquitination and subsequent activation, and achieves anti-tumor activity; ④ EGF/ERK2 signal Inhibit the GSK3β-SIRT7 axis, ERK2 inactivates GSK3β and accelerates the degradation of SIRT7; ⑤ Glucose deprivation or chemotherapy hijacks the GSK3β-SIRT7 axis through ERK2, thereby activating AKT and ensuring survival; ⑥ MEK inhibitor trametinib Can improve the efficacy of adriamycin and IF combined therapy.
[Editor-in-chief's comment]
Intermittent fasting (IF) and other dietary interventions have become a potential strategy for adjuvant cancer treatment. Liu Baohua of Shenzhen University published an article in Nature Communications and found that SIRT7 is a substrate of GSK3β. SIRT7 enhances the effect of fasting on GSK3β activity and AMPK signaling, thereby enhancing the anti-tumor effect of IF. SIRT7 can fine-tune the balance between energy stress and carcinogenic signals, thereby providing potential treatment strategies for a variety of cancers and age-related diseases. (@爱的择择)
[Original information]
Combined intermittent fasting and ERK inhibition enhance the anti-tumor effects of chemotherapy via the GSK3β-SIRT7 axis
2021-08-25, doi: 10.1038/s41467- 021-25274-3
Guangdong College of Pharmacy : how bile acids affect the intestines through FXR (review)
Gut Microbes——[10.245]
① Farnesol X receptor (FXR) Is the nuclear receptor for bile acid (BA),Widely expressed in the intestine, liver and kidney; ② FXR has an important regulatory effect on various metabolic pathways (such as glucose, lipid and sterol metabolism), and can improve obesity, liver damage, cholestasis and chronic inflammatory diseases; ③ BA connects the intestines and liver through enterohepatic circulation; ④ Different BAs have different structures and act with different to target the region, activate different receptors, and then affect downstream signal pathways and trigger different physiological functions ⑤ At present, the regulation effect of BA on intestinal microbial metabolism and intestinal mucosal inflammation still needs further study.
[Editor-in-chief's comment]
FXR is a bile acid (BAs) receptor widely found in the intestines, liver and kidneys, and has important regulatory effects on the regulation of sugars, lipids and sterols. Currently, BAs metabolites have been used in clinical liver diseases. The intestine is also an important target place for BAs. Su Zhengquan of Guangdong College of Pharmacy and Guo Jiao and their team published a review article in Gut Microbes, introducing the impact of different BAs based on FXR on the intestinal tract, and providing possible targets for the intervention of intestinal-related diseases. (@Bingbing)
[Original information]
Effect of different bile acids on the intestine through enterohepatic circulation based on FXR
2021-07-27, doi: 10.1080/19490976.2021.1949095
fat storage
Impaired ability to promote hyperlipidemia
JCI insight——[8.315]
① Include 8 insulin sensitive (IS) and insulin resistant (IR) individuals,Eating isotope-labeled lunch and dinner; ② After the start of the dinner, the lunch fat in the serum of the IS suddenly appeared ("the second meal effect"), and then the dinner fat slowly appeared, resulting in the reduction of the accumulated triglycerides (TAG) during the dinner; ③ TAG appeared faster after lunch and dinner in IR individuals, and decreased intestinal cell fat storage was related to more night activities and high blood lipids the next morning; ④ Biochemical and kinetic analysis showed that the "second meal effect" bypassed lipolysis And re-synthesis step, and rapidly secrete the TAG stored in the intestinal cells; ⑤ The above data is also consistent with the role of serum leptin change pattern in regulating dietary fat.
[Editor-in-Chief's comment]
Intestinal cells store a certain amount of fat after a meal, but its effect on lipid absorption in insulin-resistant individuals is still unknown. In this article, the study of insulin-sensitive individuals and resistant individuals found that the intestinal cells of insulin resistant individuals have impaired ability to store fat, and lipids in the blood appear faster after dinner. The storage and release of intestinal fat is related to hyperlipidemia. (@Bingbing)
[Original information]
Human intestinal lipid storage through sequential meals reveals faster dinner appearance is associated with hyperlipidemia
2021-08-09, doi: 10.1172/jci.insight.148378
SHIME Or it can be used as an effective tool to study complex flora
mSystems——[6.496]
① Use the SHIME (gastrointestinal simulator) system to perform in vitro fermentation experiments on the feces of two healthy volunteers, using the V4 variable region Amplicon sequencing samples; ② Verify the stability of samples through β diversity,It was found that the in vitro fermentation microbial community was relatively stable at 12 days, and the three compartments were clustered together, not due to the convergence of the fermentation system; ③ By detecting the longitudinal relative abundance curve of ASV, it was found that it was in the survivors, the dead and the resuscitators Evenly distributed in the three groups; ④ In vitro fermentation can enrich Akk bacteria and Bacteroides fragilis that are below the detection limit of , which may be affected by carbon source and pH; ⑤ SHIME may be an effective tool for studying human flora .
[Editor-in-Chief comment]
This article uses the SHIME (Simulator of the Human Intestinal Microbial Ecosystem) system to explore the short-term (~22-31 days) ecological adaptability and inheritance of human fecal microorganisms. The research results show that human fecal bacteria present good ecological adaptability and inheritance in the SHIME system within a certain period of time, and the system makes it possible to detect specific flora. (@Bingbing)
[Original information]
Ecological Adaptation and Succession of Human Fecal Microbial Communities in an Automated Fermentation System
2021-07-27, doi: 10.1128/mSystems.00232-21
hr8 Frequent, the greater the risk of gastrointestinal cancerJAMA Network Open——[8.483]
① 11,737,467 subjects were included, of which 319,202 (2.7%) developed gastrointestinal (GI) cancer; ②Compared to non-drinking alcohol The risk of GI cancer in light/moderate/severe drinkers is increased; ③The risk of GI cancer increases linearly with the frequency of drinking; ④The amount of alcohol consumed per drink is within 5-7 units,The risk of GI cancer increases with the increase in alcohol consumption, and each time the intake continues to increase, the HR does not increase; ⑤ When the weekly alcohol consumption is similar, the risk of GI cancer increases with the increase in drinking frequency, but with The risk pattern of esophageal cancer, gastric cancer, colorectal cancer, liver cancer, cholangiocarcinoma and pancreatic cancer is similar to that of total GI cancer.
[Editor-in-chief's comment]
The total consumption of alcohol is a risk factor for gastrointestinal (GI) cancer, but there is a lack of correlation research between the pattern of alcohol consumption and gastrointestinal cancer. According to a recent article published by JAMA Network Open, a large-scale Korean population study found that compared to the amount of alcohol consumed per drink, the frequency of alcohol consumption is a more important factor in the risk of GI cancer. (@爱的择择)
[Original information]
Association of the Frequency and Quantity of Alcohol Consumption With Gastrointestinal Cancer
2021-08-18, doi: 10.1001/jamanetworkopen.2021.20382
Thank you for this issue The creators of: mildbreeze, the choice of love, baba pulls the little magic fairy, zhihan, Johnson
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