Specifications: 0.5g×60 capsules/box
Formula (content per capsule):
Lactobacillus plantarum N-1: 25 Billion CFU
Lactobacillus johnsonii LBJ456: 25 Billion CFU
Bifidobacterium animalis HH-BAA68: 25 Billion CFU
Lactobacillus casei PB-LC39: 15 Billion CFU
Lactobacillus acidophilus HH-LA26: 10 Billion CFU
Fucoidan 80mg, Poria cocos powder 60mg, Konjac powder 60mg, galactooligosaccharide 50mg
This probiotic formula is customized to alleviate chronic kidney disease. This probiotic formula contains the patented and scientifically proven probiotic strain Lactobacillus plantarum N-1, which is scientifically proven to:
√ Relieve nephritis
√ Prevent kidney stones
Recommended dosage: For kidney disease stage 1-2, take once a day, after meals, 3-4 capsules a day, for at least two months. For stage 3-4 kidney disease, take 2 times a day, after meals, 3-4 capsules a day, for at least 4 months. For stage 5 kidney disease, take it 3 times a day, after meals, 3-4 tablets a day, for at least 6 months.
Storage method: Store away from light and at a low temperature, preferably 4°C.
All stages of chronic kidney disease
Chronic kidney disease (CKD) has five stages, which are based on how well your kidneys are working1234.
The stages are as follows: Stage 1: Mild kidney damage, eGFR 90 or higher.
Stage 2: Mild loss of kidney function, eGFR 60-89.
Stage 3a & 3b: Mild to severe loss of kidney function, eGFR 30-59.
Stage 4: Severe loss of kidney function, eGFR 15-29.
Stage 5: Kidney failure or close to failure, eGFR less than 15.
The relationship between intestinal flora and chronic kidney disease
There is a bi-directional relationship between dysbiosis and the pathogenesis of CKD. We summarized this relationship in Figure 1.:

FIGURE 1 | The relationship between the gut microbiome and chronic kidney disease (CKD) is bi-directional. In one direction, the gut microbiota affects the kidney; the emerging role of gut microbiota in (A) The healthy gut, (B) The leaky gut due to microbial dysbiosis and disruption of the mucosal layer, (C) Release of pro-inflammatory factors in the bloodstream and initiation of the inflammatory cascade, accumulation of uremic toxins, (D) A decline in the estimated glomerular filtration rate (eGFR), the elevation of the albumin creatinine ratio (ACR) and loss of the endocrine functions of the kidney. In the other direction, CKD drives dysbiosis in the gut (indicated by the dotted arrows) and initiates an inflammatory cascade.
The pathogenesis of chronic kidney disease based on intestinal microecology
1. The production of urinary toxins and the inflammatory response mechanism they induce
Under normal physiological conditions, beneficial bacteria and harmful bacteria maintain a relative balance. As CKD progresses, pathogenic bacteria grow and reproduce in large numbers, breaking the balance between beneficial bacteria and harmful bacteria, and causing changes in the intestinal ecological environment. Based on this environment, urea compensatoryly enters the intestinal lumen. Under the action of urease-expressing bacteria, urea is hydrolyzed, releasing a large amount of ammonia, and the intestinal pH value increases, which is conducive to the growth of pathogenic bacteria [1] and aggravates intestinal flora disorder. , promote the production of urinary toxins [2]. Currently, more than 90 types of uremic toxins have been reported. Although some uremic toxins can be excreted in the feces, some are absorbed and accumulated in the body of CKD patients, inducing and promoting damage to kidney structure and function in the early stages of chronic kidney disease.
2. Destruction of the intestinal barrier system and translocation of bacterial metabolites
By metabolizing food, the intestinal flora can participate in the energy supply of intestinal epithelial cells by producing short-chain fatty acids (SC-FAs); regulating the pH of the intestinal lumen, improving the acidic environment, reducing the growth of harmful bacteria; and inhibiting pro-inflammation Factor production, reducing inflammatory response [3]. The intestinal flora of CKD patients is disordered, that is, pathogenic bacteria dominate, affecting the normal physiological functions of the intestine. The intestinal barrier is damaged and leaky gut occurs [1], and bacterial metabolites are translocated, thus triggering systemic inflammation.
The positive effects of probiotics in improving chronic nephritis are mainly reflected in:
First of all, probiotic supplementation can improve the level of inflammation and oxidation in the body: by regulating serum lipopolysaccharide levels, reducing tumor necrosis factor α (TNF-α), interleukin 6 and C-reactive protein (C- reactive protein (CRP) levels; at the same time, it increases superoxide dismutase levels and total antioxidant capacity, thereby delaying the progression of kidney disease.
Furthermore, the supplementation of probiotics can reduce blood neurotoxin levels, including indoxyl sulfate (IS) p-cresyl sulfate (PCS), and other uremic toxin molecules that are difficult to remove by hemodialysis [4]. It is also accompanied by a decrease in blood urea nitrogen levels, which helps to delay the development of kidney disease. Probiotic supplementation may adjust the metabolism of intestinal flora and reduce the production level of urinary toxins. Probiotics can also help reduce organ tissue damage, including reducing glomerular and tubulointerstitial lesions; maintaining the integrity of the intestinal barrier tissue, strengthening the tight junctions between intestinal epithelial cells, and maintaining the integrity of the intestinal villus structure [5].
When chronic kidney disease progresses to the end-stage renal disease stage, patients often require kidney transplantation or long-term kidney dialysis to maintain life. Edible probiotic supplementation can have a range of positive effects on the health of kidney dialysis patients. Some population studies have shown that probiotic supplementation can improve the prevalence and incidence of vomiting, heartburn, and stomach pain in hemodialysis patients [6].
Lactobacillus plantarum N-1
Source of bacteria: Yak cheese from the Qinghai-Tibet Plateau
Collection number: CGMCC No.15463
Acid and bile salt resistance
Acid and bile tolerance are the most important properties of probiotics as they determine their ability to survive in the small intestine and thus exert their functional role as a probiotic. N-1 showed very good survival at low pH and high bile salt concentration.

adhesion
The ability to adhere to the host is an important criterion for screening potential probiotics. It is thought to be associated with colonization, pathogen suppression, immune interactions, and enhancement of barrier function. The adhesion test results showed that the adhesion number of N-1 to Caco-2 cells was 6.04×106 CFU/mL, and the adhesion rate was 4.03%.
Note: The Caco-2 cell model is a human cloned colon adenocarcinoma cell. Its structure and function are similar to differentiated small intestinal epithelial cells. It has structures such as microvilli and contains enzyme systems related to the brush border epithelium of the small intestine. It can be used to Perform experiments simulating intestinal transport in vivo.
Probiotics repair damaged intestinal barrier in chronic kidney disease
The main function of the intestinal mucosa is to absorb nutrients, secrete waste, and serve as a barrier to prevent waste absorption and prevent microorganisms and their harmful by-products in the intestinal lumen from entering the human body's internal environment [7-8].

According to the H & E staining results of the rat colon in Figure 2, compared with the sham operation group, the crypt depth and mucosal thickness of the colon tissue in the model group were significantly reduced (P<0.05); and compared with the model group, the probiotics The crypt depth and mucosal thickness of the group were significantly increased (P<0.05), indicating that the morphology of the colonic mucosa was restored to a certain extent after probiotic administration. The concentration of dopamine in the brains of mice in the daily probiotic group reached a statistical difference, which increased by 27% compared with the disease-causing group, and the effect was significant.
Effects of probiotics on colon epithelial tight junction proteins in rats with chronic kidney disease
According to Figure 4, after oral administration of probiotics, the levels of ZO-1 and Claudin-1 proteins in the colon of rats increased significantly (P<0.05), indicating that probiotics can repair the damaged intestinal tight junctions to a certain extent. , reduce harmful substances and antigens in the intestines from entering the body, and inhibit the body's immune response.

2.4 Effect of mixed probiotics on serum cytokines in rats with chronic kidney disease
Experiments have shown that compared with the sham operation group, the C-reactive protein content in the serum of rats in the model group was significantly increased, indicating that rats in the model group experienced systemic inflammation. This phenomenon may be caused by the damage to the intestinal barrier and the After intragastric administration of probiotics caused by lipopolysaccharide entering the body, the C-reactive protein content in the serum of rats in the probiotic group was significantly reduced compared with the rats in the model group, indicating that this probiotic product can effectively inhibit the inflammatory response in rats with kidney disease. Combined with previous experimental results, probiotic intervention can repair intestinal barrier damage caused by renal insufficiency. Probiotics may reduce intestinal microorganisms and other foreign matter entering the body by improving the damaged intestinal barrier, thereby reducing inflammation in rats with kidney disease. Phenomenon. In addition, compared with the sham operation group, the levels of pro-inflammatory factors TNF-α (P<0.05) and IL-6 (P>0.05) in the serum of rats in the model group were increased, and the levels of anti-inflammatory factor IL-10 (P<0.05) were increased. and IL-13 (P<0.05) significantly decreased, indicating that the innate immune system in rats with chronic kidney disease was stimulated, which was consistent with the results of C-reactive protein. Compared with the probiotic group, the levels of pro-inflammatory factors TNF-α (P<0.05) and IL-6 (P>0.05) in the serum of rats in the probiotic group decreased. The levels of anti-inflammatory factors IL-10 (P<0.05) and IL-13 (P< 0.05) content increased significantly, indicating that probiotics improve the immune imbalance and inflammatory response in rats by regulating the levels of pro-inflammatory factors and anti-inflammatory factors in the serum.

Raw materials from the same origin as medicine and food:
fucoidan
Fucoidan, called fucoidan or fucoidan, is a marine complex polysaccharide composed of fucose-containing sulfate groups. Fucoidan can improve the gastrointestinal tract, be an active polysaccharide, and has good effects on treating chronic renal failure and enhancing immunity.
Konjac powder
Glucomannan contained in konjac has strong swelling power and is more viscous and tougher than any kind of vegetable gum. It can fill the intestines and stomach, detoxify and reduce swelling, and widen the intestines to relieve constipation. The dietary fiber in konjac can promote gastrointestinal motility and clear bowel movements. The accumulation of fat in the intestines allows toxic substances to be excreted from the body, soothes the intestines, detoxifies, and cleanses the stomach.
Poria powder
Poria cocos powder is the powder of the traditional Chinese medicine Poria cocos. It is usually white or light gray and turns dark gray after brewing. It is mild in nature, sweet, and light in taste, and contains triterpenes, polysaccharides, choline, fat, lecithin, potassium, magnesium, and other elements. It has the effects of diuresis and dampness, strengthening the spleen and calming the heart. Poria cocos can not only significantly improve the body's immunity, but also cause oxyhemoglobin in the blood to release more oxygen to supply tissue cells.
Articles & Patents
1. JAZANI NH, SAVOJ J, LUSTGARTEN M, et al. Impact of gut dysbiosis on neurohormonal pathways in chronic kidney disease[J]. Diseases, 2019,7(1): 21.
2. YANG T, RICHARDS EM, PEPINE CJ, et al. The gut microbiota and the brain-gut-kidney axis in hypertension and chronic kidney disease[J]. Nat Rev Nephrol, 2018, 14(7): 442-456.
3. 刘松珍, 张雁, 张名位, 等. 肠道短链脂肪酸产生机制及生理功能的研究进展[ J]. 广东农业科学, 2013, 40 ( 11): 99 -103.
4. LOPES R, THEODORO J M V, DA SILVA B P, et al. Synbiotic meal decreases uremic toxins in hemodialysis individuals: a placebo-controlled trial[J]. Food Research International, 2019, 116: 241-248.
5. LIOR L, CAO Y G, KATHRIN F, et al. Diet posttranslationally modifies the mouse gut microbial proteome to modulate renal function[J]. Science, 2020, 369: 1518-1524.
6. VIRAMONTES-HORNER D, MARQUEZ-SANDOVAL F, MARTINDEL-CAMPO F, et al. Effect of a symbiotic gel (Lactobacillus acidophilus + Bifidobacterium lactis + inulin) on the presence and severity of gastrointestinal symptoms in hemodialysis patients[J]. Journal of Renal Nutrition, 2015, 25(3): 284-291.
7. CAMILLER M, MADSEN K, SPILLER R. Intestinal barrier function in health and gastrointestinal disease[J].Neurogastroenterology and Motility,2012, 24(6):503-512.
8. MATTHEW A O, JERROLD R T. The intestinal epithelial barrier: a therapeutic target[J].Nature Reviews Gastroenterology & Hepatology,2017,14(1):9-12.
9. LEE B T, AHMED F A, HAMM L L, et al. Association of C-reactive protein, tumor necrosis factor-alpha, and interleukin-6 with chronic kidney disease[J]. BMC Nephrology,2015,16(1):1-6.
10. YEUN J Y, LEVINE R A, MANTA V, et al. C-reactive protein predicts all-cause and cardiovascular mortality in hemodialysis patients[J]. American Journal of Kidney Diseases,2000,35(3):469-476.
11. MACHOWAKA A, CARRERO J J , LINDHOLM B ,et al. Therapeutics targeting persistent inflammation in chronic kidney disease[J]. Translational Research,2016,167(1):204-213.
12. STENVINKEL P, KETTELER M,JOHNSON R J,et al.IL-10, IL-6 and TNF-alpha: Central factors in the altered cytokine network of uremia-the good, the bad, and the ugly [J]. Kidney International,2005,67(4):1216-1233.
13. GIRNDT M, GUZMAN N J, BALAKRISHNAN V S,et al. Association between albuminuria, kidney function, and inflammatory biomarker profile in CKD in CRIC[J]. Clinical Journal of the American Society of Nephrology,2012,7(12):1938-1946.
14. WANG I K, WU Y Y, YANG Y F, et al. The effect of probiotics on serum levels of cytokine and endotoxin in peritoneal dialysis Patients: a randomized, double-blind, placebo-controlled trial [J]. Beneficial Microbes, 2015, 6(4):423-430.
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