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    Home > Biochemistry News > Microbiology News > Lactobacillus casei can slow down the progression of chronic kidney disease, phase 1 clinical data is gratifying

    Lactobacillus casei can slow down the progression of chronic kidney disease, phase 1 clinical data is gratifying

    • Last Update: 2021-08-26
    • Source: Internet
    • Author: User
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    Original title: Sub-Journal of "Cell": China's probiotics make great contributions! Scientists have discovered for the first time that Lactobacillus casei can slow down the progression of chronic kidney disease.
    Phase 1 clinical data is gratifying | Clinical discovery

    China’s star probiotic-Lactobacillus casei Zhang, isolated from natural fermented mare milk in Inner Mongolia, is China’s first complete strain Genome sequencing of lactic acid bacteria [1]
    .
    The bacteria is acid and bile resistant, and can be stably colonized in the human gastrointestinal tract
    .


    Oral Lactobacillus casei Zhang can regulate the human immune response and intestinal microbial composition, and can specifically enhance the anti-inflammatory and antioxidant effects of healthy adults and the elderly [2]
    .
    In addition, it has also been found to alleviate acute liver injury and insulin resistance induced by lipopolysaccharide by regulating the production of intestinal microbial-derived metabolites [3-4]
    .
    However, Lactobacillus casei Zhang has not conducted preclinical studies and human trials in kidney disease
    .


    Recently, a research team led by Professor Zeng Rui, Professor Yao Ying, and Professor Xu Gang from Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology published important research results in the journal Cell Metabolism [5]
    .


      The team demonstrated for the first time that supplementing with Lactobacillus casei Zhang (Lac.
    z) can reduce acute kidney injury (AKI) in mice and slow the development of chronic nephropathy
    .
    In addition, a phase 1 clinical study on patients with chronic kidney disease (stage 3-5) shows that Lac.
    z is safe and beneficial to the human body and can alleviate the decline in renal function of patients
    .
    The study shows that Lactobacillus casei Zhang can reduce kidney damage and slow the development of chronic nephropathy by improving the intestinal flora and increasing the levels of short-chain fatty acids (SCFAs) and nicotinamide in the serum and kidney
    .
    This research result reveals the potential of Lac.
    z in alleviating kidney disease, and provides new treatment strategies and potential treatment methods for chronic kidney disease
    .

    Pattern diagram

      Although the intestinal flora is closely related to kidney disease, it remains to be elucidated how the intestinal flora affects kidney disease
    .
    In addition, it is still controversial whether the supplement of probiotics can be used for the prevention and treatment of kidney disease
    .


      To study the effect of Lac.
    z on kidney disease in mice, the researchers took orally Lac.
    z or Lactobacillus acidophilus (Lact) (10 9   CFU/day) on male C57BL/6 mice for 4 consecutive weeks, and then the mice Kidney ischemia-reperfusion (I/R) induces acute kidney injury
    .


      The researchers found that compared with the group without probiotics, the acute kidney injury of the mice in the probiotic group (5th day after I/R) was significantly smaller, and Lac.
    z was more effective than Lact (Figure 1B)
    .
    In addition, probiotics can not only reduce serum urea nitrogen (BUN) and creatinine (an indicator of renal function improvement), but also reduce pathological damages such as necrosis, renal tubular dilatation, and cast formation
    .
    The effect of probiotic Lac.
    z is significantly better than Lact
    .
    The researchers extended the observation time to 28 days and 45 days after I/R, and found that the renal interstitial fibrosis was improved by supplementing with probiotics
    .
    In addition, compared with Lact, Lac.
    z is more effective in preventing renal fibrosis
    .



    Figure 1.
    Oral Lac.
    z can reduce acute kidney injury induced by ischemia-reperfusion I/R in both kidneys (Sham: sham operation group; IR: ischemia-reperfusion treatment group; IR+Lact: treatment group + eosinophilic milk supplement Bacillus; IR+Lac.
    z: treatment group + supplemented with Lactobacillus casei Zhang)

      In order to further explore the underlying mechanism, the researchers performed fecal 16S rRNA sequencing on mice.
    Interestingly, mouse gut bacteria on day 5 (AKI model) and day 28 (CKD model) after I/R induced kidney injury Group imbalance, and supplementation of probiotic Lac.
    z can increase the diversity of intestinal bacteria α and β and the number of Bacteroides phylum in mice, thereby improving the imbalance of intestinal flora induced by I/R
    .


      Given that in mice supplemented with probiotics, the number of bacteria (such as Bacteroides) that produce SCFAs on the 5th day after I/R increases
    .
    The researchers further used GC-MS to detect the concentration of SCFAs in mouse serum and kidney.
    The researchers found that after supplementing Lac.
    z, the contents of propionic acid and butyric acid in the mice were significantly increased
    .
    Furthermore, the investigators designed an intervention experiment that was fed with acetic acid, propionic acid, butyric acid or a mixture of the three through drinking water before I/R was started, and lasted for 2 weeks
    .
    Sure enough, SCFAs alleviated I/R-induced AKI and CKD caused by AKI (Figure 2D-E)
    .



     
    Figure 2.
    Lac.
    z induces SCFAs to alleviate I/R-mediated kidney injury

      In order to better understand the effects of probiotics on the metabolism of mice, the researchers used metabolomics to find that the nicotinamide metabolism (including nicotinamide adenine dinucleotide NAD and niacin) in the control group (I/R day 5) Adenine dinucleotide (NAAD) was significantly lower, and the content of nicotinamide in the Lac.
    z supplemented group was higher than that of the untreated control group
    .
    Researchers have further confirmed that supplementation of Lac.
    z can significantly reduce kidney damage and neutrophil infiltration through nicotinamide supplement experiments in mice
    .
    This shows that Lac.
    z can promote the activation of kidney NAD+ biosynthesis and reduce kidney damage
    .


      The data from the animal model fully proves the renal protective effect of the probiotic Lac.
    z, but the mouse model cannot fully reflect the actual situation of the human body
    .
    Therefore, in order to further verify the role of Lac.
    z in humans, the researchers enrolled 62 patients with stage 3-5 CKD (n = 62) for a phase 1 clinical trial, and randomized them to receive placebo (n = 29).
    ) Or Lac.
    z treatment (1*10 9   CFU/day) (n = 33) for 3 months
    .


      Clinical studies have shown that the placebo group's serum cystatin C (a measure of renal function) significantly increased, while the Lac.
    z group's serum cystatin C level decreased, and was significantly lower than the placebo group (Figure 3B)
    .
    In the placebo group, serum parathyroid hormone increased significantly after 3 months, while the Lac.
    z group decreased after 3 months (Figure 3C)
    .


      In addition, the urinary albumin-creatinine ratio (UACR) of the placebo group increased significantly after 3 months, while the Lac.
    z group only slightly increased, indicating that Lac.
    z can delay the progression of CKD
    .


      Because the 3-month observation period was too short to observe changes in creatinine, the researchers extended the average follow-up time of the placebo group and the probiotic group to 13 months
    .
    The increase in creatinine in the Lac.
    z group was lower .
    In addition, the results of serum metabolomics showed that in the placebo group, the level of niacinamide was significantly reduced, while in the Lac.
    z group, niacinamide remained stable
    .


      In addition, the researchers also calculated the monthly decrease rate of glomerular filtration rate (eGFR).
    The average decrease rate of eGFR in the probiotic group was 0.
    07±0.
    18 mL/(min*1.
    73m²)/month, which was significantly lower than 0.
    58 in the placebo group.
    ±0.
    14 mL/(min*1.
    73m²)/month, these results show that Lac.
    z can slow down the progress of CKD
    .



    Figure 3.
    Human clinical studies show that Lac.
    z can reduce the decline of renal function in patients with chronic nephropathy CKD

      Serum Cystatin C (B) and Serum Parathyroid Hormone (C) measured after 3 months of treatment with placebo or L.
    casei Zhang

      I am very excited to see such a beautiful job! The domestic research team cooperated with domestic star probiotic strains, rigorous zoology tests and human clinical trials, and used multi-omics technologies (transcriptome, 16S rRNA sequencing, single-cell transcriptome, metabolome) to in-depth study of Lactobacillus casei Zhang's role in the kidneys The biological mechanism of protection
    .


      This research result shows the potential of Lactobacillus casei Zhang in reducing acute kidney injury and slowing down the progression of chronic kidney disease, providing a new idea for the prevention and treatment of kidney disease
    .


      This research is not only another fruit of the "gut-renal axis" theory, but also a benchmark in the field of probiotic research in my country! Looking forward to larger double-blind randomized controlled trials in the future to further evaluate the clinical utility of Lactobacillus casei Zhang
    .


    References:

    [1] Zhang W, Yu D, Sun Z, et al.
    Complete genome sequence of Lactobacillus casei Zhang, a new probiotic strain isolated from traditional homemade koumiss in Inner Mongolia, China.
    J Bacteriol.
    2010;192(19) :5268-5269.
    doi:10.
    1128/JB.
    00802-10

    [2] Wu R, Wang W, Yu D, et al.
    Proteomics analysis of Lactobacillus casei Zhang, a new probiotic bacterium isolated from traditional home-made koumiss in Inner Mongolia of China.
    Mol Cell Proteomics.
    2009;8(10): 2321-2338.
    doi:10.
    1074/mcp.
    M800483-MCP200

    [3]Wang Y, Xie J, Li Y, et al.
    Probiotic Lactobacillus casei Zhang reduces pro-inflammatory cytokine production and hepatic inflammation in a rat model of acute liver failure.
    Eur J Nutr.
    2016;55(2):821-831.
    doi:10.
    1007/s00394-015-0904-3

    [4]Zhang Y, Wang L, Zhang J, et al.
    Probiotic Lactobacillus casei Zhang ameliorates high-fructose- induced impaired glucose tolerance in hyperinsulinemia rats.
    Eur J Nutr.
    2014;53(1):221-232.
    doi:10.
    1007/s00394-013-0519-5

    [5] Zhu H, Cao C, Wu Z, et al.
    The probiotic L.
    casei Zhang slows the progression of acute and chronic kidney disease [published online ahead of print, 2021 Jul 8].
    Cell Metab.
    2021;S1550-4131 (21)00284-9.
    doi:10.
    1016/j.
    cmet.
    2021.
    06.
    014


     

    Disclaimer: This article only represents the author's personal views and has nothing to do with China Probiotics.
    com
    .
    The originality and the text and content stated in the article have not been verified by this site.
    This site does not make any guarantee or commitment to the authenticity, completeness, and timeliness of this article, all or part of the content, and the text.
    Readers are invited for reference only, and please Verify the relevant content yourself
    .
     

    Copyright notice

    1.
    Some of the reprinted articles on this site are not original, and the copyright and liability belong to the original author
    .
    2.
    All reprinted articles, links and pictures on this website are for the purpose of conveying more information, and clearly indicate the source and author.
    Media or individuals who do not want to be reprinted can contact us for infringement information that can provide sufficient evidence , Bio149 will be deleted within 12 hours after confirmation
    .
    3.
    Users are welcome to post original articles to 86371366@qq.
    com, and publish them to the homepage after review.
    The copyright and liability belong to the sender
    .


      Original title: Sub-Journal of "Cell": China's probiotics make great contributions! Scientists have discovered for the first time that Lactobacillus casei can slow down the progression of chronic kidney disease.
    Phase 1 clinical data is gratifying | Clinical discovery

      China’s star probiotic-Lactobacillus casei Zhang, isolated from natural fermented mare milk in Inner Mongolia, is China’s first complete strain Genome sequencing of lactic acid bacteria [1]
    .
    The bacteria is acid and bile resistant, and can be stably colonized in the human gastrointestinal tract
    .


      Oral Lactobacillus casei Zhang can regulate the human immune response and intestinal microbial composition, and can specifically enhance the anti-inflammatory and antioxidant effects of healthy adults and the elderly [2]
    .
    In addition, it has also been found to alleviate acute liver injury and insulin resistance induced by lipopolysaccharide by regulating the production of intestinal microbial-derived metabolites [3-4]
    .
    However, Lactobacillus casei Zhang has not conducted preclinical studies and human trials in kidney disease
    .


      Recently, a research team led by Professor Zeng Rui, Professor Yao Ying, and Professor Xu Gang from Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology published important research results in the journal Cell Metabolism [5]
    .


      The team demonstrated for the first time that supplementing with Lactobacillus casei Zhang (Lac.
    z) can reduce acute kidney injury (AKI) in mice and slow the development of chronic nephropathy
    .
    In addition, a phase 1 clinical study on patients with chronic kidney disease (stage 3-5) shows that Lac.
    z is safe and beneficial to the human body and can alleviate the decline in renal function of patients
    .
    The study shows that Lactobacillus casei Zhang can reduce kidney damage and slow the development of chronic nephropathy by improving the intestinal flora and increasing the levels of short-chain fatty acids (SCFAs) and nicotinamide in the serum and kidney
    .
    This research result reveals the potential of Lac.
    z in alleviating kidney disease, and provides new treatment strategies and potential treatment methods for chronic kidney disease
    .

    Pattern diagram

      Although the intestinal flora is closely related to kidney disease, it remains to be elucidated how the intestinal flora affects kidney disease
    .
    In addition, it is still controversial whether the supplement of probiotics can be used for the prevention and treatment of kidney disease
    .


      To study the effect of Lac.
    z on kidney disease in mice, the researchers took orally Lac.
    z or Lactobacillus acidophilus (Lact) (10 9   CFU/day) on male C57BL/6 mice for 4 consecutive weeks, and then the mice Kidney ischemia-reperfusion (I/R) induces acute kidney injury
    .


      The researchers found that compared with the group without probiotics, the acute kidney injury of the mice in the probiotic group (5th day after I/R) was significantly smaller, and Lac.
    z was more effective than Lact (Figure 1B)
    .
    In addition, probiotics can not only reduce serum urea nitrogen (BUN) and creatinine (an indicator of renal function improvement), but also reduce pathological damages such as necrosis, renal tubular dilatation, and cast formation
    .
    The effect of probiotic Lac.
    z is significantly better than Lact
    .
    The researchers extended the observation time to 28 days and 45 days after I/R, and found that the renal interstitial fibrosis was improved by supplementing with probiotics
    .
    In addition, compared with Lact, Lac.
    z is more effective in preventing renal fibrosis
    .



    Figure 1.
    Oral Lac.
    z can reduce acute kidney injury induced by ischemia-reperfusion I/R in both kidneys (Sham: sham operation group; IR: ischemia-reperfusion treatment group; IR+Lact: treatment group + eosinophilic milk supplement Bacillus; IR+Lac.
    z: treatment group + supplemented with Lactobacillus casei Zhang)

      In order to further explore the underlying mechanism, the researchers performed fecal 16S rRNA sequencing on mice.
    Interestingly, mouse gut bacteria on day 5 (AKI model) and day 28 (CKD model) after I/R induced kidney injury Group imbalance, and supplementation of probiotic Lac.
    z can increase the diversity of intestinal bacteria α and β and the number of Bacteroides phylum in mice, thereby improving the imbalance of intestinal flora induced by I/R
    .


      Given that in mice supplemented with probiotics, the number of bacteria (such as Bacteroides) that produce SCFAs on the 5th day after I/R increases
    .
    The researchers further used GC-MS to detect the concentration of SCFAs in mouse serum and kidney.
    The researchers found that after supplementing Lac.
    z, the contents of propionic acid and butyric acid in the mice were significantly increased
    .
    Furthermore, the investigators designed an intervention experiment that was fed with acetic acid, propionic acid, butyric acid or a mixture of the three through drinking water before I/R was started, and lasted for 2 weeks
    .
    Sure enough, SCFAs alleviated I/R-induced AKI and CKD caused by AKI (Figure 2D-E)
    .



     
    Figure 2.
    Lac.
    z induces SCFAs to alleviate I/R-mediated kidney injury

      In order to better understand the effects of probiotics on the metabolism of mice, the researchers used metabolomics to find that the nicotinamide metabolism (including nicotinamide adenine dinucleotide NAD and niacin) in the control group (I/R day 5) Adenine dinucleotide (NAAD) was significantly lower, and the content of nicotinamide in the Lac.
    z supplemented group was higher than that of the untreated control group
    .
    Researchers have further confirmed that supplementation of Lac.
    z can significantly reduce kidney damage and neutrophil infiltration through nicotinamide supplement experiments in mice
    .
    This shows that Lac.
    z can promote the activation of kidney NAD+ biosynthesis and reduce kidney damage
    .


      The data from the animal model fully proves the renal protective effect of the probiotic Lac.
    z, but the mouse model cannot fully reflect the actual situation of the human body
    .
    Therefore, in order to further verify the role of Lac.
    z in humans, the researchers enrolled 62 patients with stage 3-5 CKD (n = 62) for a phase 1 clinical trial, and randomized them to receive placebo (n = 29).
    ) Or Lac.
    z treatment (1*10 9   CFU/day) (n = 33) for 3 months
    .


      Clinical studies have shown that the placebo group's serum cystatin C (a measure of renal function) significantly increased, while the Lac.
    z group's serum cystatin C level decreased, and was significantly lower than the placebo group (Figure 3B)
    .
    In the placebo group, serum parathyroid hormone increased significantly after 3 months, while the Lac.
    z group decreased after 3 months (Figure 3C)
    .


      In addition, the urinary albumin-creatinine ratio (UACR) of the placebo group increased significantly after 3 months, while the Lac.
    z group only slightly increased, indicating that Lac.
    z can delay the progression of CKD
    .


      Because the 3-month observation period was too short to observe changes in creatinine, the researchers extended the average follow-up time of the placebo group and the probiotic group to 13 months
    .
    The increase in creatinine in the Lac.
    z group was lower .
    In addition, the results of serum metabolomics showed that in the placebo group, the level of niacinamide was significantly reduced, while in the Lac.
    z group, niacinamide remained stable
    .


      In addition, the researchers also calculated the monthly decrease rate of glomerular filtration rate (eGFR).
    The average decrease rate of eGFR in the probiotic group was 0.
    07±0.
    18 mL/(min*1.
    73m²)/month, which was significantly lower than 0.
    58 in the placebo group.
    ±0.
    14 mL/(min*1.
    73m²)/month, these results show that Lac.
    z can slow down the progress of CKD
    .



    Figure 3.
    Human clinical studies show that Lac.
    z can reduce the decline of renal function in patients with chronic nephropathy CKD

      Serum Cystatin C (B) and Serum Parathyroid Hormone (C) measured after 3 months of treatment with placebo or L.
    casei Zhang

      I am very excited to see such a beautiful job! The domestic research team cooperated with domestic star probiotic strains, rigorous zoology tests and human clinical trials, and used multi-omics technologies (transcriptome, 16S rRNA sequencing, single-cell transcriptome, metabolome) to in-depth study of Lactobacillus casei Zhang's role in the kidneys The biological mechanism of protection
    .


      This research result shows the potential of Lactobacillus casei Zhang in reducing acute kidney injury and slowing down the progression of chronic kidney disease, providing a new idea for the prevention and treatment of kidney disease
    .


      This research is not only another fruit of the "gut-renal axis" theory, but also a benchmark in the field of probiotic research in my country! Looking forward to larger double-blind randomized controlled trials in the future to further evaluate the clinical utility of Lactobacillus casei Zhang
    .


    References:

    [1] Zhang W, Yu D, Sun Z, et al.
    Complete genome sequence of Lactobacillus casei Zhang, a new probiotic strain isolated from traditional homemade koumiss in Inner Mongolia, China.
    J Bacteriol.
    2010;192(19) :5268-5269.
    doi:10.
    1128/JB.
    00802-10

    [2] Wu R, Wang W, Yu D, et al.
    Proteomics analysis of Lactobacillus casei Zhang, a new probiotic bacterium isolated from traditional home-made koumiss in Inner Mongolia of China.
    Mol Cell Proteomics.
    2009;8(10): 2321-2338.
    doi:10.
    1074/mcp.
    M800483-MCP200

    [3]Wang Y, Xie J, Li Y, et al.
    Probiotic Lactobacillus casei Zhang reduces pro-inflammatory cytokine production and hepatic inflammation in a rat model of acute liver failure.
    Eur J Nutr.
    2016;55(2):821-831.
    doi:10.
    1007/s00394-015-0904-3

    [4]Zhang Y, Wang L, Zhang J, et al.
    Probiotic Lactobacillus casei Zhang ameliorates high-fructose- induced impaired glucose tolerance in hyperinsulinemia rats.
    Eur J Nutr.
    2014;53(1):221-232.
    doi:10.
    1007/s00394-013-0519-5

    [5] Zhu H, Cao C, Wu Z, et al.
    The probiotic L.
    casei Zhang slows the progression of acute and chronic kidney disease [published online ahead of print, 2021 Jul 8].
    Cell Metab.
    2021;S1550-4131 (21)00284-9.
    doi:10.
    1016/j.
    cmet.
    2021.
    06.
    014


     

    Disclaimer: This article only represents the author's personal views and has nothing to do with China Probiotics.
    com
    .
    The originality and the text and content stated in the article have not been verified by this site.
    This site does not make any guarantee or commitment to the authenticity, completeness, and timeliness of this article, all or part of the content, and the text.
    Readers are invited for reference only, and please Verify the relevant content yourself
    .
     

    Copyright notice

    1.
    Some of the reprinted articles on this site are not original, and the copyright and liability belong to the original author
    .
    2.
    All reprinted articles, links and pictures on this website are for the purpose of conveying more information, and clearly indicate the source and author.
    Media or individuals who do not want to be reprinted can contact us for infringement information that can provide sufficient evidence , Bio149 will be deleted within 12 hours after confirmation
    .
    3.
    Users are welcome to post original articles to 86371366@qq.
    com, and publish them to the homepage after review.
    The copyright and liability belong to the sender
    .


      Original title: Sub-Journal of "Cell": China's probiotics make great contributions! Scientists have discovered for the first time that Lactobacillus casei can slow down the progression of chronic kidney disease.
    Phase 1 clinical data is gratifying | Clinical discovery

      China’s star probiotic-Lactobacillus casei Zhang, isolated from natural fermented mare milk in Inner Mongolia, is China’s first complete strain Genome sequencing of lactic acid bacteria [1]
    .
    The bacteria is acid and bile resistant, and can be stably colonized in the human gastrointestinal tract
    .


      Oral Lactobacillus casei Zhang can regulate the human immune response and intestinal microbial composition, and can specifically enhance the anti-inflammatory and antioxidant effects of healthy adults and the elderly [2]
    .
    In addition, it has also been found to alleviate acute liver injury and insulin resistance induced by lipopolysaccharide by regulating the production of intestinal microbial-derived metabolites [3-4]
    .
    However, Lactobacillus casei Zhang has not conducted preclinical studies and human trials in kidney disease
    .


      Recently, a research team led by Professor Zeng Rui, Professor Yao Ying, and Professor Xu Gang from Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology published important research results in the journal Cell Metabolism [5]
    .


      The team demonstrated for the first time that supplementing with Lactobacillus casei Zhang (Lac.
    z) can reduce acute kidney injury (AKI) in mice and slow the development of chronic nephropathy
    .
    In addition, a phase 1 clinical study on patients with chronic kidney disease (stage 3-5) shows that Lac.
    z is safe and beneficial to the human body and can alleviate the decline in renal function of patients
    .
    The study shows that Lactobacillus casei Zhang can reduce kidney damage and slow the development of chronic nephropathy by improving the intestinal flora and increasing the levels of short-chain fatty acids (SCFAs) and nicotinamide in the serum and kidney
    .
    This research result reveals the potential of Lac.
    z in alleviating kidney disease, and provides new treatment strategies and potential treatment methods for chronic kidney disease
    .

    Pattern diagram

      Although the intestinal flora is closely related to kidney disease, it remains to be elucidated how the intestinal flora affects kidney disease
    .
    In addition, it is still controversial whether the supplement of probiotics can be used for the prevention and treatment of kidney disease
    .


      To study the effect of Lac.
    z on kidney disease in mice, the researchers took orally Lac.
    z or Lactobacillus acidophilus (Lact) (10 9   CFU/day) on male C57BL/6 mice for 4 consecutive weeks, and then the mice Kidney ischemia-reperfusion (I/R) induces acute kidney injury
    .


      The researchers found that compared with the group without probiotics, the acute kidney injury of the mice in the probiotic group (5th day after I/R) was significantly smaller, and Lac.
    z was more effective than Lact (Figure 1B)
    .
    In addition, probiotics can not only reduce serum urea nitrogen (BUN) and creatinine (an indicator of renal function improvement), but also reduce pathological damages such as necrosis, renal tubular dilatation, and cast formation
    .
    The effect of probiotic Lac.
    z is significantly better than Lact
    .
    The researchers extended the observation time to 28 days and 45 days after I/R, and found that the renal interstitial fibrosis was improved by supplementing with probiotics
    .
    In addition, compared with Lact, Lac.
    z is more effective in preventing renal fibrosis
    .



    Figure 1.
    Oral Lac.
    z can reduce acute kidney injury induced by ischemia-reperfusion I/R in both kidneys (Sham: sham operation group; IR: ischemia-reperfusion treatment group; IR+Lact: treatment group + eosinophilic milk supplement Bacillus; IR+Lac.
    z: treatment group + supplemented with Lactobacillus casei Zhang)

      In order to further explore the underlying mechanism, the researchers performed fecal 16S rRNA sequencing on mice.
    Interestingly, mouse gut bacteria on day 5 (AKI model) and day 28 (CKD model) after I/R induced kidney injury Group imbalance, and supplementation of probiotic Lac.
    z can increase the diversity of intestinal bacteria α and β and the number of Bacteroides phylum in mice, thereby improving the imbalance of intestinal flora induced by I/R
    .


      Given that in mice supplemented with probiotics, the number of bacteria (such as Bacteroides) that produce SCFAs on the 5th day after I/R increases
    .
    The researchers further used GC-MS to detect the concentration of SCFAs in mouse serum and kidney.
    The researchers found that after supplementing Lac.
    z, the contents of propionic acid and butyric acid in the mice were significantly increased
    .
    Furthermore, the investigators designed an intervention experiment that was fed with acetic acid, propionic acid, butyric acid or a mixture of the three through drinking water before I/R was started, and lasted for 2 weeks
    .
    Sure enough, SCFAs alleviated I/R-induced AKI and CKD caused by AKI (Figure 2D-E)
    .



     
    Figure 2.
    Lac.
    z induces SCFAs to alleviate I/R-mediated kidney injury

      In order to better understand the effects of probiotics on the metabolism of mice, the researchers used metabolomics to find that the nicotinamide metabolism (including nicotinamide adenine dinucleotide NAD and niacin) in the control group (I/R day 5) Adenine dinucleotide (NAAD) was significantly lower, and the content of nicotinamide in the Lac.
    z supplemented group was higher than that of the untreated control group
    .
    Researchers have further confirmed that supplementation of Lac.
    z can significantly reduce kidney damage and neutrophil infiltration through nicotinamide supplement experiments in mice
    .
    This shows that Lac.
    z can promote the activation of kidney NAD+ biosynthesis and reduce kidney damage
    .


      The data from the animal model fully proves the renal protective effect of the probiotic Lac.
    z, but the mouse model cannot fully reflect the actual situation of the human body
    .
    Therefore, in order to further verify the role of Lac.
    z in humans, the researchers enrolled 62 patients with stage 3-5 CKD (n = 62) for a phase 1 clinical trial, and randomized them to receive placebo (n = 29).
    ) Or Lac.
    z treatment (1*10 9   CFU/day) (n = 33) for 3 months
    .


      Clinical studies have shown that the placebo group's serum cystatin C (a measure of renal function) significantly increased, while the Lac.
    z group's serum cystatin C level decreased, and was significantly lower than the placebo group (Figure 3B)
    .
    In the placebo group, serum parathyroid hormone increased significantly after 3 months, while the Lac.
    z group decreased after 3 months (Figure 3C)
    .


      In addition, the urinary albumin-creatinine ratio (UACR) of the placebo group increased significantly after 3 months, while the Lac.
    z group only slightly increased, indicating that Lac.
    z can delay the progression of CKD
    .


      Because the 3-month observation period was too short to observe changes in creatinine, the researchers extended the average follow-up time of the placebo group and the probiotic group to 13 months
    .
    The increase in creatinine in the Lac.
    z group was lower .
    In addition, the results of serum metabolomics showed that in the placebo group, the level of niacinamide was significantly reduced, while in the Lac.
    z group, niacinamide remained stable
    .


      In addition, the researchers also calculated the monthly decrease rate of glomerular filtration rate (eGFR).
    The average decrease rate of eGFR in the probiotic group was 0.
    07±0.
    18 mL/(min*1.
    73m²)/month, which was significantly lower than 0.
    58 in the placebo group.
    ±0.
    14 mL/(min*1.
    73m²)/month, these results show that Lac.
    z can slow down the progress of CKD
    .



    Figure 3.
    Human clinical studies show that Lac.
    z can reduce the decline of renal function in patients with chronic nephropathy CKD

      Serum Cystatin C (B) and Serum Parathyroid Hormone (C) measured after 3 months of treatment with placebo or L.
    casei Zhang

      I am very excited to see such a beautiful job! The domestic research team cooperated with domestic star probiotic strains, rigorous zoology tests and human clinical trials, and used multi-omics technologies (transcriptome, 16S rRNA sequencing, single-cell transcriptome, metabolome) to in-depth study of Lactobacillus casei Zhang's role in the kidneys The biological mechanism of protection
    .


      This research result shows the potential of Lactobacillus casei Zhang in reducing acute kidney injury and slowing down the progression of chronic kidney disease, providing a new idea for the prevention and treatment of kidney disease
    .


      This research is not only another fruit of the "gut-renal axis" theory, but also a benchmark in the field of probiotic research in my country! Looking forward to larger double-blind randomized controlled trials in the future to further evaluate the clinical utility of Lactobacillus casei Zhang
    .


    References:

    [1] Zhang W, Yu D, Sun Z, et al.
    Complete genome sequence of Lactobacillus casei Zhang, a new probiotic strain isolated from traditional homemade koumiss in Inner Mongolia, China.
    J Bacteriol.
    2010;192(19) :5268-5269.
    doi:10.
    1128/JB.
    00802-10

    [2] Wu R, Wang W, Yu D, et al.
    Proteomics analysis of Lactobacillus casei Zhang, a new probiotic bacterium isolated from traditional home-made koumiss in Inner Mongolia of China.
    Mol Cell Proteomics.
    2009;8(10): 2321-2338.
    doi:10.
    1074/mcp.
    M800483-MCP200

    [3]Wang Y, Xie J, Li Y, et al.
    Probiotic Lactobacillus casei Zhang reduces pro-inflammatory cytokine production and hepatic inflammation in a rat model of acute liver failure.
    Eur J Nutr.
    2016;55(2):821-831.
    doi:10.
    1007/s00394-015-0904-3

    [4]Zhang Y, Wang L, Zhang J, et al.
    Probiotic Lactobacillus casei Zhang ameliorates high-fructose- induced impaired glucose tolerance in hyperinsulinemia rats.
    Eur J Nutr.
    2014;53(1):221-232.
    doi:10.
    1007/s00394-013-0519-5

    [5] Zhu H, Cao C, Wu Z, et al.
    The probiotic L.
    casei Zhang slows the progression of acute and chronic kidney disease [published online ahead of print, 2021 Jul 8].
    Cell Metab.
    2021;S1550-4131 (21)00284-9.
    doi:10.
    1016/j.
    cmet.
    2021.
    06.
    014


     

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      :《》:!,,1 |

      —— Zhang,,[1]
    。、,


      Zhang,[2]
    。,[3-4]
    。, Zhang


      ,、Cell Metabolism[5]


       Zhang(Lac.
    z)(AKI)
    。,(3-5)1Lac.
    z,
    。 Zhang,(SCFAs),,
    。Lac.
    z,
    。  :《》:!,,1 | Cell Metabolism

      ,



      Lac.
    z,C57BL/64,Lac.
    z(Lact)(109  CFU /),(I/R)


      ,,(I/R5),Lac.
    zLact(1B)
    。,(BUN)(),、、
    。Lac.
    zLact
    。I/R28、45,
    。,Lact,Lac.
    z
    9
    1.
    Lac.
    zI/R(Sham:;IR: ;IR+Lact:+;IR+Lac.
    z: + Zhang)
    Figure 1.
    Oral Lac.
    z can reduce acute kidney injury induced by ischemia-reperfusion I/R in both kidneys (Sham: sham operation group; IR: ischemia-reperfusion treatment group; IR+Lact: treatment group + eosinophilic milk supplement Bacillus; IR+Lac.
    z: treatment group + supplemented with Lactobacillus casei Zhang)
      In order to further explore the underlying mechanism, the researchers performed fecal 16S rRNA sequencing on mice.
    Interestingly, on the 5th day after I/R induced kidney injury (AKI model) and the 28th day (CKD model) the intestinal flora of mice is imbalanced, and supplementation of probiotic Lac.
    z can increase the diversity of mouse intestinal bacteria α and β and the number of Bacteroides phylum, thereby improving I/R The intestinal flora imbalance caused by induction
    .


      Given that in mice supplemented with probiotics, the number of bacteria (such as Bacteroides) that produce SCFAs on the 5th day after I/R increases
    .
    The researchers further used GC-MS to detect the concentration of SCFAs in mouse serum and kidney.
    The researchers found that after supplementing Lac.
    z, the contents of propionic acid and butyric acid in the mice were significantly increased
    .
    Furthermore, the investigators designed an intervention experiment that was fed with acetic acid, propionic acid, butyric acid or a mixture of the three through drinking water before I/R was started, and lasted for 2 weeks
    .
    Sure enough, SCFAs alleviated I/R-induced AKI and CKD caused by AKI (Figure 2D-E)
    .

     

    Figure 2.
    Lac.
    z induces SCFAs to alleviate I/R-mediated kidney injury
    Figure 2.
    Lac.
    z induces SCFAs to alleviate I/R-mediated kidney injury.

      In order to better understand the effects of probiotics on the metabolism of mice, the researchers used metabolomics to find that the control group (I/R day 5) Nicotinamide metabolism (including nicotinamide adenine dinucleotide NAD and niacin adenine dinucleotide NAAD) was significantly lower, while the content of nicotinamide in the Lac.
    z supplement group was higher than that of the untreated control group
    .
    Researchers have further confirmed that supplementation of Lac.
    z can significantly reduce kidney damage and neutrophil infiltration through nicotinamide supplement experiments in mice
    .
    This shows that Lac.
    z can promote the activation of kidney NAD+ biosynthesis and reduce kidney damage
    .


      The data from the animal model fully proves the renal protective effect of the probiotic Lac.
    z, but the mouse model cannot fully reflect the actual situation of the human body
    .
    Therefore, in order to further verify the role of Lac.
    z in humans, the researchers enrolled 62 patients with stage 3-5 CKD (n = 62) for a phase 1 clinical trial, and randomized them to receive placebo (n = 29).
    ) Or Lac.
    z treatment (1*10 9   CFU/day) (n = 33) for 3 months
    .


      Clinical studies have shown that the placebo group's serum cystatin C (a measure of renal function) significantly increased, while the Lac.
    z group's serum cystatin C level decreased, and was significantly lower than the placebo group (Figure 3B)
    .
    In the placebo group, serum parathyroid hormone increased significantly after 3 months, while the Lac.
    z group decreased after 3 months (Figure 3C)
    .


      In addition, the urinary albumin-creatinine ratio (UACR) of the placebo group increased significantly after 3 months, while the Lac.
    z group only slightly increased, indicating that Lac.
    z can delay the progression of CKD
    .


      Because the 3-month observation period was too short to observe changes in creatinine, the researchers extended the average follow-up time of the placebo group and the probiotic group to 13 months.
    The increase in creatinine in the Lac.
    z group was lower.

    .
    In addition, the results of serum metabolomics showed that in the placebo group, the level of niacinamide was significantly reduced, while in the Lac.
    z group, niacinamide remained stable
    .


      In addition, the researchers also calculated the monthly decrease rate of glomerular filtration rate (eGFR).
    The average decrease rate of eGFR in the probiotic group was 0.
    07±0.
    18 mL/(min*1.
    73m²)/month, which was significantly lower than 0.
    58 in the placebo group.
    ±0.
    14 mL/(min*1.
    73m²)/month, these results show that Lac.
    z can slow down the progress of CKD
    .
    9
    Figure 3.
    Human clinical studies show that Lac.
    z can reduce the decline of renal function in patients with chronic nephropathy CKD
    Figure 3.
    Human clinical studies have shown that Lac.
    z can reduce the decline of renal function in patients with chronic nephropathy CKD.

      Placebo or L.
    casei Zhang measured serum cystatin C (B) and serum parathyroid hormone (C )

      Very excited to see such a beautiful job! The domestic research team cooperated with domestic star probiotic strains, rigorous zoology tests and human clinical trials, and used multi-omics technologies (transcriptome, 16S rRNA sequencing, single-cell transcriptome, metabolome) to in-depth study of Lactobacillus casei Zhang's role in the kidneys The biological mechanism of protection
    .


      This research result shows the potential of Lactobacillus casei Zhang in reducing acute kidney injury and slowing down the progression of chronic kidney disease, providing a new idea for the prevention and treatment of kidney disease
    .


      This research is not only another fruit of the "gut-renal axis" theory, but also a benchmark in the field of probiotic research in my country! Looking forward to larger double-blind randomized controlled trials in the future to further evaluate the clinical utility of Lactobacillus casei Zhang
    .


    References:

    [1] Zhang W, Yu D, Sun Z, et al.
    Complete genome sequence of Lactobacillus casei Zhang, a new probiotic strain isolated from traditional homemade koumiss in Inner Mongolia, China.
    J Bacteriol.
    2010;192(19) :5268-5269.
    doi:10.
    1128/JB.
    00802-10

    [2] Wu R, Wang W, Yu D, et al.
    Proteomics analysis of Lactobacillus casei Zhang, a new probiotic bacterium isolated from traditional home-made koumiss in Inner Mongolia of China.
    Mol Cell Proteomics.
    2009;8(10): 2321-2338.
    doi:10.
    1074/mcp.
    M800483-MCP200

    [3]Wang Y, Xie J, Li Y, et al.
    Probiotic Lactobacillus casei Zhang reduces pro-inflammatory cytokine production and hepatic inflammation in a rat model of acute liver failure.
    Eur J Nutr.
    2016;55(2):821-831.
    doi:10.
    1007/s00394-015-0904-3

    [4]Zhang Y, Wang L, Zhang J, et al.
    Probiotic Lactobacillus casei Zhang ameliorates high-fructose- induced impaired glucose tolerance in hyperinsulinemia rats.
    Eur J Nutr.
    2014;53(1):221-232.
    doi:10.
    1007/s00394-013-0519-5

    [5] Zhu H, Cao C, Wu Z, et al.
    The probiotic L.
    casei Zhang slows the progression of acute and chronic kidney disease [published online ahead of print, 2021 Jul 8].
    Cell Metab.
    2021;S1550-4131 (21)00284-9.
    doi:10.
    1016/j.
    cmet.
    2021.
    06.
    014

     
     
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