human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND AND OBJECTIVES The generation of key uremic nephrovascular toxins , indoxyl sulfate ( IS ) , and p-cresyl sulfate ( PCS ) , is attributed to the dysbiotic gut microbiota in CKD . The aim of our study was to evaluate whether synbiotic ( pre- and probiotic ) therapy alters the gut microbiota and reduces serum concentrations of microbiome-generated uremic toxins , IS and PCS , in patients with CKD . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS Predialysis adult participants with CKD ( eGFR=10 - 30 ml/min per 1.73 m(2 ) ) were recruited between January 5 , 2013 and November 12 , 2013 to a r and omized , double-blind , placebo-controlled , crossover trial of synbiotic therapy over 6 weeks ( 4-week washout ) . The primary outcome was serum IS . Secondary outcomes included serum PCS , stool microbiota profile , eGFR , proteinuria-albuminuria , urinary kidney injury molecule-1 , serum inflammatory biomarkers ( IL-1β , IL-6 , IL-10 , and TNF-α ) , serum oxidative stress biomarkers ( F2-isoprostanes and glutathione peroxidase ) , serum LPS , patient-reported health , Gastrointestinal Symptom Score , and dietary intake . A prespecified subgroup analysis explored the effect of antibiotic use on treatment effect . RESULTS Of 37 individuals r and omized ( age = 69±10 years old ; 57 % men ; eGFR=24±8 ml/min per 1.73 m(2 ) ) , 31 completed the study .  Synbiotic therapy did not significantly reduce serum IS ( -2 μmol/L ; 95 % confidence interval [ 95 % CI ] , -5 to 1 μmol/L ) but did significantly reduce serum PCS ( -14 μmol/L ; 95 % CI , -27 to -2 μmol/L ) . Decreases in both PCS and IS concentrations were more pronounced in patients who did not receive antibiotics during the study ( n=21 ; serum PCS , -25 μmol/L ; 95 % CI , -38 to -12 μmol/L ; serum IS , -5 μmol/L ; 95 % CI , -8 to -1 μmol/L ) . Synbiotics also altered the stool microbiome , particularly with enrichment of Bifidobacterium and depletion of Ruminococcaceae . Except for an increase in albuminuria of 38 mg/24 h ( P=0.03 ) in the synbiotic arm , no changes were observed in the other secondary outcomes . CONCLUSION In patients with CKD , synbiotics did not significantly reduce serum IS but did decrease serum PCS and favorably modified the stool microbiome . Large-scale clinical trials are justified Gastrointestinal ( GI ) symptoms and irritable bowel ( IB ) symptoms have been associated with chronic fatigue syndrome/myalgic encephalomyelitis ( CFS/ME ) . The aim of this study was to conduct a systematic review of these symptoms in CFS/ME , along with any evidence for probiotics as treatment . Pubmed , Scopus , Medline ( EBSCOHost ) and EMBASE data bases were search ed to source relevant studies for CFS/ME . The review included any studies examining GI symptoms , irritable bowel syndrome ( IBS ) and /or probiotic use . Studies were required to report criteria for CFS/ME and study design , intervention and outcome measures . Quality assessment was also completed to summarise the level of evidence available . A total of 3381 publications were returned using our search terms . Twenty-five studies were included in the review . R and omised control trials were the predominant study type ( n = 24 ) . Most of the studies identified examined the effect of  probiotic supplementation on the improvement of IB symptoms in IBS patients , or IB symptoms in CFS/ME patients , as well as some other significant secondary outcomes ( e.g. quality of life , other gastrointestinal symptoms , psychological symptoms ) . The level of evidence identified for the use of  probiotics  in IBS was excellent in quality ; however , the evidence available for the use of probiotic interventions in CFS/ME was poor and limited . There is currently insufficient evidence for the use of probiotics in CFS/ME patients , despite probiotic interventions being useful in IBS . The studies pertaining to probiotic interventions in CFS/ME patients were limited and of poor quality overall . St and ardisation of protocol s and methodology in these studies is required Components present in the diet , l-carnitine , choline , and betaine are metabolized by gut microbiota to produce metabolites such as trimethylamine-N-oxide ( TMAO ) that appear to promote cardiovascular disease in chronic kidney disease ( CKD ) patients . The objective of this pilot study was to evaluate the effects of probiotic supplementation for 3 months on plasma TMAO levels in CKD patients on hemodialysis ( HD ) . A r and omized , double-blind trial was performed in 21 patients [ 54.8 ± 10.4 years , nine men , BMI 26.1 ± 4.8 kg/m2 , dialysis vintage 68.5 ( 34.2–120.7 ) months ] . Ten patients were r and omly allocated to the placebo group and 11 to the probiotic group [ three capsules , totaling 9 × 1013 colony-forming units per day of Streptococcus thermophilus ( KB19 ) , Lactobacillus acidophilus ( KB27 ) , and Bifidobacteria longum ( KB31 ) . Plasma TMAO , choline , and betaine levels were measured by LC-MS/MS at baseline and after 3 months . While TMAO did not change after probiotic supplementation , there was a significant increase in betaine plasma levels . In contrast , the placebo group showed a significant decrease in plasma choline levels . Short-term probiotic supplementation does not appear to influence plasma TMAO levels in HD patients . Long-term studies are needed to determine whether probiotics may affect TMAO production in CKD patients ABSTRACT Aim : This was a pilot clinical trial to assess biochemical and clinical effects of an oral probiotic dietary supplement in chronic kidney disease ( CKD ) patients ( stages 3 and 4 ) . Methods : A prospect i ve , r and omized , double-blind , crossover , placebo-controlled , 6-month trial of probiotic bacteria was conducted in 16 out patients in Ontario , Canada . Primary endpoints included effect on hematologic , biochemical , and fecal variables , and on general well-being as assessed by quality of life ( QOL ) . These outcomes were evaluated from biochemical parameters , mainly blood urea nitrogen ( BUN ) , creatinine , uric acid , and C-reactive protein ( CRP ) as a general inflammatory marker . QOL was assessed on a subjective scale of 1 to 10 as the secondary parameter . Trial registration : This pilot study forms part of registered trial NCT00760162 . Results : A total of 13 patients completed the study . Three patients dropped out : one was the receiver of a transplant . The second dropped out for unknown reasons and the third died of myocardial infa rct ion ( unrelated to probiotic bacteria or the protocol ) . Among the 13 patients who completed the trial , the mean change in BUN concentration during the probiotic treatment period ( −2.93 mmol/L ) differed significantly ( p = 0.002 ) from the mean change in BUN concentration during the placebo period ( 4.52 mmol/L ) . In addition , the mean changes in uric acid concentration were moderate during the KB period ( 24.70 μmol/L ) versus during the placebo period ( 50.62 μmol/L , p = 0.050 ) , and the changes in serum creatinine concentration were insignificant . Neither gastrointestinal nor infectious complications were noted in any subject with improved QOL . Conclusion : Orally administered probiotic bacteria selected to metabolize nitrogenous wastes may be tolerated for as long as 6 months . A major limitation of this trial is its small size that may have precluded detection of changes in other biochemical or hematologic parameters that would be evident in larger cohorts . Extension of the evaluation of this probiotic bacterial mixture will include a dose escalation trial in a similar prospect i ve , placebo-controlled , and double-blind study site The present study was to test the hypothesis that selected bacteria instilled into the gastrointestinal tract could help in converting nitrogenous wastes accumulated due to renal insufficiency into nontoxic compounds ; thereby , ameliorating the biochemical imbalance . Herein we describe a prospect i ve , blinded , placebo-controlled pilot study , using 5/6th nephrectomized Sprague Dawley rat as a chronic renal failure model . The study group consisted of 36 nephrectomized and 7 non-nephrectomized ( control ) rats . After two-week nephrectomy stabilization , cohorts of six nephrectomized rats were fed casein-based diet plus one of the following regimens : ( A ) Control , ( B ) Placebo ( casein-based diet without probiotics ) , ( C ) Bacillus pasteurii , ( D ) Sporolac ® , ( E ) Kibow cocktail , ( F ) CHR Hansen Cocktail , and ( G ) ECONORMTM .  Subsequently , blood ( retro-orbital ) and urine ( collected for measurements of blood urea-nitrogen and creatinine respectively ) , body weight and bacterial counts ( feces ) were obtained at regular intervals . The study end-points were to determine if any of the probiotic dietary supplements facilitated , ( 1 ) decreased blood concentrations of uremic toxins , ( 2 ) altered renal function , and ( 3 ) prolonged survival . After 16 weeks of treatment , regimens C and D significantly prolonged the life span of uremic rats , in addition to showing a reduction in blood urea-nitrogen levels , concluding that supplementation of probiotic formulation to uremic rats slows the progression of azotemia , which may correlate with prolonged life span of uremic rats . Derivative trials of probiotic treatment of larger animals and humans will further assess the potential role of probiotic formulations in delaying the onset and clinical severity of clinical illness at different stages of renal failure BACKGROUND AND AIMS In patients with chronic kidney disease ( CKD ) , alterations in gut microbiome are posited to be responsible for gastrointestinal symptoms and generation of p-cresol , a uremic toxin that has been associated with CKD progression and cardiovascular mortality . This pilot study investigated whether Probinul-neutro ® , a synbiotic that normalizes intestinal microflora , may lower plasma p-cresol concentrations and reduce gastrointestinal symptoms in non-dialyzed CKD patients . METHODS AND RESULTS This was a double-blind , r and omized placebo-controlled trial . Thirty patients on 3 - 4 CKD stages were r and omized to receive either Probinul neutro ® or placebo for 4 weeks . Total plasma p-cresol concentration was assessed at baseline , and 15 and 30 days after treatment start . At the same study times , ease and frequency of defecation , upper and lower abdominal pain , stool shape , borborygmi , and flatus were quantified by subjective assessment question naires . Compared to baseline total plasma p-cresol median concentrations on 15th and 30th day were significantly lower in patients receiving Probinul-neutro ® ( 2.31 and 0.78 vs. 3.05 μg/ml , p < 0.05 ; n = 18 ) ; no changes of plasma p-cresol concentrations were recorded in placebo-treated patients . No significant changes in gastrointestinal symptoms were observed during the study both in Probinul-neutro ® -treated and placebo-treated patients . CONCLUSION Probinul-neutro ® lowered total plasma p-cresol concentrations but did not ameliorate gastrointestinal symptoms in non-dialyzed CKD patients . Because high plasma concentrations of p-cresol in early phases of CKD are predictive of progression to end-stage renal disease , the results of our study suggest that synbiotics deserve attention as possible tools to delay CKD progression towards end-stage renal disease ( ESRD ) . CLINICAL TRIALSGOV IDENTIFIER NCT02008331 OBJECTIVE The study aim ed to assess the effect of a symbiotic gel on presence and severity of gastrointestinal symptoms ( GIS ) in hemodialysis patients . DESIGN A double-blinded , placebo-controlled , r and omized , clinical trial was design ed . The study was conducted at 2 public hospitals in Guadalajara , Mexico . SUBJECTS AND INTERVENTION Twenty-two patients were r and omized to the intervention group ( nutritional counseling + symbiotic gel )  and 20 patients were r and omized to the control group ( nutritional counseling + placebo )  , during 2 months of follow-up . MAIN OUTCOME MEASURE Presence and monthly episodes of GIS were assessed by direct interview and severity by using the self-administered GIS question naire . 
    Output:
    
agent
Conclusion Our study demonstrates potential beneficial effects of probiotics on inflammation , uremic toxins , and GI Symptoms in ESRD patients .
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND AND OBJECTIVES The generation of key uremic nephrovascular toxins , indoxyl sulfate ( IS ) , and p-cresyl sulfate ( PCS ) , is attributed to the dysbiotic gut microbiota in CKD . The aim of our study was to evaluate whether synbiotic ( pre- and probiotic ) therapy alters the gut microbiota and reduces serum concentrations of microbiome-generated uremic toxins , IS and PCS , in patients with CKD . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS Predialysis adult participants with CKD ( eGFR=10 - 30 ml/min per 1.73 m(2 ) ) were recruited between January 5 , 2013 and November 12 , 2013 to a r and omized , double-blind , placebo-controlled , crossover trial of synbiotic therapy over 6 weeks ( 4-week washout ) . The primary outcome was serum IS . Secondary outcomes included serum PCS , stool microbiota profile , eGFR , proteinuria-albuminuria , urinary kidney injury molecule-1 , serum inflammatory biomarkers ( IL-1β , IL-6 , IL-10 , and TNF-α ) , serum oxidative stress biomarkers ( F2-isoprostanes and glutathione peroxidase ) , serum LPS , patient-reported health , Gastrointestinal Symptom Score , and dietary intake . A prespecified subgroup analysis explored the effect of antibiotic use on treatment effect . RESULTS Of 37 individuals r and omized ( age = 69±10 years old ; 57 % men ; eGFR=24±8 ml/min per 1.73 m(2 ) ) , 31 completed the study .  Synbiotic therapy did not significantly reduce serum IS ( -2 μmol/L ; 95 % confidence interval [ 95 % CI ] , -5 to 1 μmol/L ) but did significantly reduce serum PCS ( -14 μmol/L ; 95 % CI , -27 to -2 μmol/L ) . Decreases in both PCS and IS concentrations were more pronounced in patients who did not receive antibiotics during the study ( n=21 ; serum PCS , -25 μmol/L ; 95 % CI , -38 to -12 μmol/L ; serum IS , -5 μmol/L ; 95 % CI , -8 to -1 μmol/L ) . Synbiotics also altered the stool microbiome , particularly with enrichment of Bifidobacterium and depletion of Ruminococcaceae . Except for an increase in albuminuria of 38 mg/24 h ( P=0.03 ) in the synbiotic arm , no changes were observed in the other secondary outcomes . CONCLUSION In patients with CKD , synbiotics did not significantly reduce serum IS but did decrease serum PCS and favorably modified the stool microbiome . Large-scale clinical trials are justified Gastrointestinal ( GI ) symptoms and irritable bowel ( IB ) symptoms have been associated with chronic fatigue syndrome/myalgic encephalomyelitis ( CFS/ME ) . The aim of this study was to conduct a systematic review of these symptoms in CFS/ME , along with any evidence for probiotics as treatment . Pubmed , Scopus , Medline ( EBSCOHost ) and EMBASE data bases were search ed to source relevant studies for CFS/ME . The review included any studies examining GI symptoms , irritable bowel syndrome ( IBS ) and /or probiotic use . Studies were required to report criteria for CFS/ME and study design , intervention and outcome measures . Quality assessment was also completed to summarise the level of evidence available . A total of 3381 publications were returned using our search terms . Twenty-five studies were included in the review . R and omised control trials were the predominant study type ( n = 24 ) . Most of the studies identified examined the effect of  probiotic supplementation on the improvement of IB symptoms in IBS patients , or IB symptoms in CFS/ME patients , as well as some other significant secondary outcomes ( e.g. quality of life , other gastrointestinal symptoms , psychological symptoms ) . The level of evidence identified for the use of  probiotics  in IBS was excellent in quality ; however , the evidence available for the use of probiotic interventions in CFS/ME was poor and limited . There is currently insufficient evidence for the use of probiotics in CFS/ME patients , despite probiotic interventions being useful in IBS . The studies pertaining to probiotic interventions in CFS/ME patients were limited and of poor quality overall . St and ardisation of protocol s and methodology in these studies is required Components present in the diet , l-carnitine , choline , and betaine are metabolized by gut microbiota to produce metabolites such as trimethylamine-N-oxide ( TMAO ) that appear to promote cardiovascular disease in chronic kidney disease ( CKD ) patients . The objective of this pilot study was to evaluate the effects of probiotic supplementation for 3 months on plasma TMAO levels in CKD patients on hemodialysis ( HD ) . A r and omized , double-blind trial was performed in 21 patients [ 54.8 ± 10.4 years , nine men , BMI 26.1 ± 4.8 kg/m2 , dialysis vintage 68.5 ( 34.2–120.7 ) months ] . Ten patients were r and omly allocated to the placebo group and 11 to the probiotic group [ three capsules , totaling 9 × 1013 colony-forming units per day of Streptococcus thermophilus ( KB19 ) , Lactobacillus acidophilus ( KB27 ) , and Bifidobacteria longum ( KB31 ) . Plasma TMAO , choline , and betaine levels were measured by LC-MS/MS at baseline and after 3 months . While TMAO did not change after probiotic supplementation , there was a significant increase in betaine plasma levels . In contrast , the placebo group showed a significant decrease in plasma choline levels . Short-term probiotic supplementation does not appear to influence plasma TMAO levels in HD patients . Long-term studies are needed to determine whether probiotics may affect TMAO production in CKD patients ABSTRACT Aim : This was a pilot clinical trial to assess biochemical and clinical effects of an oral probiotic dietary supplement in chronic kidney disease ( CKD ) patients ( stages 3 and 4 ) . Methods : A prospect i ve , r and omized , double-blind , crossover , placebo-controlled , 6-month trial of probiotic bacteria was conducted in 16 out patients in Ontario , Canada . Primary endpoints included effect on hematologic , biochemical , and fecal variables , and on general well-being as assessed by quality of life ( QOL ) . These outcomes were evaluated from biochemical parameters , mainly blood urea nitrogen ( BUN ) , creatinine , uric acid , and C-reactive protein ( CRP ) as a general inflammatory marker . QOL was assessed on a subjective scale of 1 to 10 as the secondary parameter . Trial registration : This pilot study forms part of registered trial NCT00760162 . Results : A total of 13 patients completed the study . Three patients dropped out : one was the receiver of a transplant . The second dropped out for unknown reasons and the third died of myocardial infa rct ion ( unrelated to probiotic bacteria or the protocol ) . Among the 13 patients who completed the trial , the mean change in BUN concentration during the probiotic treatment period ( −2.93 mmol/L ) differed significantly ( p = 0.002 ) from the mean change in BUN concentration during the placebo period ( 4.52 mmol/L ) . In addition , the mean changes in uric acid concentration were moderate during the KB period ( 24.70 μmol/L ) versus during the placebo period ( 50.62 μmol/L , p = 0.050 ) , and the changes in serum creatinine concentration were insignificant . Neither gastrointestinal nor infectious complications were noted in any subject with improved QOL . Conclusion : Orally administered probiotic bacteria selected to metabolize nitrogenous wastes may be tolerated for as long as 6 months . A major limitation of this trial is its small size that may have precluded detection of changes in other biochemical or hematologic parameters that would be evident in larger cohorts . Extension of the evaluation of this probiotic bacterial mixture will include a dose escalation trial in a similar prospect i ve , placebo-controlled , and double-blind study site The present study was to test the hypothesis that selected bacteria instilled into the gastrointestinal tract could help in converting nitrogenous wastes accumulated due to renal insufficiency into nontoxic compounds ; thereby , ameliorating the biochemical imbalance . Herein we describe a prospect i ve , blinded , placebo-controlled pilot study , using 5/6th nephrectomized Sprague Dawley rat as a chronic renal failure model . The study group consisted of 36 nephrectomized and 7 non-nephrectomized ( control ) rats . After two-week nephrectomy stabilization , cohorts of six nephrectomized rats were fed casein-based diet plus one of the following regimens : ( A ) Control , ( B ) Placebo ( casein-based diet without probiotics ) , ( C ) Bacillus pasteurii , ( D ) Sporolac ® , ( E ) Kibow cocktail , ( F ) CHR Hansen Cocktail , and ( G ) ECONORMTM .  Subsequently , blood ( retro-orbital ) and urine ( collected for measurements of blood urea-nitrogen and creatinine respectively ) , body weight and bacterial counts ( feces ) were obtained at regular intervals . The study end-points were to determine if any of the probiotic dietary supplements facilitated , ( 1 ) decreased blood concentrations of uremic toxins , ( 2 ) altered renal function , and ( 3 ) prolonged survival . After 16 weeks of treatment , regimens C and D significantly prolonged the life span of uremic rats , in addition to showing a reduction in blood urea-nitrogen levels , concluding that supplementation of probiotic formulation to uremic rats slows the progression of azotemia , which may correlate with prolonged life span of uremic rats . Derivative trials of probiotic treatment of larger animals and humans will further assess the potential role of probiotic formulations in delaying the onset and clinical severity of clinical illness at different stages of renal failure BACKGROUND AND AIMS In patients with chronic kidney disease ( CKD ) , alterations in gut microbiome are posited to be responsible for gastrointestinal symptoms and generation of p-cresol , a uremic toxin that has been associated with CKD progression and cardiovascular mortality . This pilot study investigated whether Probinul-neutro ® , a synbiotic that normalizes intestinal microflora , may lower plasma p-cresol concentrations and reduce gastrointestinal symptoms in non-dialyzed CKD patients . METHODS AND RESULTS This was a double-blind , r and omized placebo-controlled trial . Thirty patients on 3 - 4 CKD stages were r and omized to receive either Probinul neutro ® or placebo for 4 weeks . Total plasma p-cresol concentration was assessed at baseline , and 15 and 30 days after treatment start . At the same study times , ease and frequency of defecation , upper and lower abdominal pain , stool shape , borborygmi , and flatus were quantified by subjective assessment question naires . Compared to baseline total plasma p-cresol median concentrations on 15th and 30th day were significantly lower in patients receiving Probinul-neutro ® ( 2.31 and 0.78 vs. 3.05 μg/ml , p < 0.05 ; n = 18 ) ; no changes of plasma p-cresol concentrations were recorded in placebo-treated patients . No significant changes in gastrointestinal symptoms were observed during the study both in Probinul-neutro ® -treated and placebo-treated patients . CONCLUSION Probinul-neutro ® lowered total plasma p-cresol concentrations but did not ameliorate gastrointestinal symptoms in non-dialyzed CKD patients . Because high plasma concentrations of p-cresol in early phases of CKD are predictive of progression to end-stage renal disease , the results of our study suggest that synbiotics deserve attention as possible tools to delay CKD progression towards end-stage renal disease ( ESRD ) . CLINICAL TRIALSGOV IDENTIFIER NCT02008331 OBJECTIVE The study aim ed to assess the effect of a symbiotic gel on presence and severity of gastrointestinal symptoms ( GIS ) in hemodialysis patients . DESIGN A double-blinded , placebo-controlled , r and omized , clinical trial was design ed . The study was conducted at 2 public hospitals in Guadalajara , Mexico . SUBJECTS AND INTERVENTION Twenty-two patients were r and omized to the intervention group ( nutritional counseling + symbiotic gel )  and 20 patients were r and omized to the control group ( nutritional counseling + placebo )  , during 2 months of follow-up . MAIN OUTCOME MEASURE Presence and monthly episodes of GIS were assessed by direct interview and severity by using the self-administered GIS question naire . 
    Output:
    