The effect of β-glucan prebiotic fibre (oats) on the gut microbiome of chronic kidney disease patients (Stage IV and V) and impact on kidney function

Ebrahim, Zarina (2022-04)

Thesis (PhD)--Stellenbosch University, 2022.

Thesis

ENGLISH SUMMARY: Background: Chronic kidney disease (CKD) is increasing in global prevalence and has many nutritional complications. Increasing evidence suggests that gut dysbiosis is involved in CKD progression through various mechanisms including intestinally derived uraemic toxins, dietary, and immune-mediated factors. Therefore, modulating the gut microbiome may improve outcomes in CKD. The aim of this research project was to investigate the effect of a ß-glucan prebiotic supplement on kidney outcomes, uraemic toxins and the gut microbiome in predialysis CKD participants. Methods: This study was a randomised controlled intervention study over 18 weeks, performed at Tygerberg Hospital predialysis clinic in Cape Town, South Africa. There was a pre-randomisation period of four weeks where participants were counselled on a CKD diet before being randomised. At randomisation, the intervention group received the ß-glucan supplement and continued the diet, while the control group continued with the diet only. There were follow-ups at weeks 4, 8 and 14 after randomisation. The objectives were to assess nutritional status, kidney function, plasma levels of uraemic toxins and gut microbiota using 16S rRNA sequencing at pre-randomisation. Additionally, differences in these outcomes were measured at randomisation baseline (week 0), week 8 and week 14 between the intervention and the control groups. Anthropometrical measurements were done which included weight, height, waist circumference, mid-upper arm circumference and triceps. Clinical investigations included investigating for oedema as well as gastrointestinal symptom measurement. Stool consistency was described using the Bristol Stool Score (BSS). Dietary intake was measured using a quantified food frequency questionnaire (QFFQ) and a dietary adherence score sheet. Although most of the investigations was done locally, the uraemic toxins analysis was performed at the nephrology laboratories at the University of Ghent in Belgium, while the gut microbiome analysis was performed at VIB laboratories (Leuven, Belgium). Statistical analysis was performed using IBM®SPSS®version 26/27 and R Statistical Software. Results: Seventy participants were enrolled in the study at the pre-randomisation visit. The mean age of the participants was 41.7 ± 11.8 years, with a slight predominance of females (53%). Most participants were unemployed, earning less than US$126 per month. Hypertension was the main cause of kidney failure and most participants were in stage 5 CKD. A very high prevalence of overweight (30%) and obesity (36%) was found at pre-randomisation, with a low prevalence of undernutrition (3%). Abdominal obesity was found in 60% of participants. Dietary assessment showed an unhealthy dietary pattern. After four weeks, 59 participants were randomised. The diet intervention resulted in significant nutritional changes in participants after four weeks, while uraemic toxins remained unchanged. There was a significant reduction in body mass index (P < 0.006) and waist circumference (P < 0.001). Almost all dietary intake variables were significantly reduced and there was a high dietary adherence. Serum total cholesterol (P < 0.045) and triglyceride levels (P < 0.017) were also reduced. After randomisation to either the ß-glucan prebiotic or the diet, kidney function did not significantly change. However, there was a significant reduction in uraemic toxins in free IxS at week 8 (P = 0.003) and week 14 (P < 0.001), total and free pCG (P < 0.001, P < 0.001, respectively) and free pCS (P = 0.006) at week 14. There were no significant changes in dietary intake, clinical symptoms or anthropometry during the trial. The gut microbiome revealed that two enterotypes were prevalent, namely the Bacteroides2 and Prevotella enterotypes. The inter-individual Bray–Curtis distance (ß-diversity) was significantly higher in the control group than the intervention group at baseline (P < 0.0001), week 8 (P < 0.0001) and week 14 (P = 0.02). There were no differences in relative abundance of genera between groups. The redundancy analysis showed a few factors significantly affected the gut microbiome: these included triglyceride levels (P < 0.001), cause of kidney failure (P < 0.001), gender (P < 0.001), body mass index (P = 0.002), high- density lipoprotein (P < 0.001) and the prebiotic intervention (P = 0.002). Conclusion:While four weeks of the diet resulted in some nutritional changes in participants before randomisation, it did not affect other outcomes of the study. Once randomised, the prebiotic did not significantly affect kidney function, while it significantly reduced uraemic toxins and the gut microbiome, according to the RDA analysis. The ß-glucan prebiotic therefore had some beneficial effects on outcomes in CKD participants.

AFRIKAANSE OPSOMMING: Agtergrond: Chroniese niersiekte (CNS) se voorkoms wêreldwyd neem toe en het talle voedingskomplikasies. Toenemende getuienis dui daarop dat dermdisbiose deur verskillende meganismes, insluitend intestinaal afgeleide uremiese toksiene, en dieet- en immuun-bemiddelde faktore, by die vordering van CNS betrokke is. Die modulering van die dermmikrobioom kan dus uitkomste in CNS verbeter. Die doel van hierdie navorsingsprojek was om die effek van ’n ß-glukaan- prebiotiese supplement op nieruitkomste, uremiese toksiene en die dermmikrobioom by voordialise-CNS-deelnemers te ondersoek. Metodes: Hierdie studie was ’n ewekansige gekontroleerde intervensiestudie oor 18 weke wat by die Tygerberg Hospitaal se voordialisekliniek in Kaapstad, Suid-Afrika uitgevoer is. Daar was ’n voor-ewekansigingsperiode van vier weke waar deelnemers dieetonderriging ontvang het oor ’n CNS-dieet voordat hulle ewekansig is. Met ewekansiging het die intervensiegroep die ß-glukaansupplement ontvang en met die dieet voortgegaan, terwyl die kontrolegroep slegs met die dieet voortgegaan het. Daar was opvolgbesoeke in week 4, 8 en 14 ná ewekansiging. Die doelwitte was om voedingstatus, nierfunksie, plasmavlakke van uremiese toksiene en dermmikrobiotika met behulp van 16S rRNS- volgordebepaling met voor-ewekansiging te evalueer. Verder is verskille in hierdie uitkomste met die ewekansigingsbasislyn (week 0), week 8 en week 14 tussen die intervensie- en kontrolegroep gemeet. Antropometriese metings is gedoen, wat gewig, lengte, middelyfomtrek, mid-bo-arm omtrek en triseps ingesluit het. Kliniese ondersoeke het ’n ondersoek vir edeem asook die meting van gastroïntestinale simptome ingesluit. Stoelgangtekstuur is met behulp van die Bristol-stoelgangtelling (Bristol Stool Score) beskryf. Dieetinname is met behulp van ’n voedselfrekwensievraelys gedoen en dieetnakoming is gemeet. Hoewel die meeste van die ondersoeke plaaslik gedoen is, is die uremiesetoksienontleding by die nefrologielaboratoriums van die Universiteit van Ghent in België gedoen, terwyl die dermmikrobioomontleding by VIB-laboratoriums (Leuven, België) gedoen is. Resultate: Sewentig deelnemers is met die voor-ewekansigingsbesoek vir die studie ingeskryf. Die gemiddelde ouderdom van die deelnemers was 41.7 ± 11.8 jaar, met ’n geringe oorheersing van vroue (53%). Die meeste deelnemers was werkloos en het minder as US$126 per maand verdien. Hipertensie was die vernaamste oorsaak van nierversaking en die meeste deelnemers was op stadium 5 CNS.’n Baie hoë voorkoms van oorgewig (30%) en vetsug (36%) is met voor-ewekansiging gekry, met ’n lae voorkoms van ondervoeding (3%). Abdominale vetsug is by 60% van die deelnemers gevind. ’n Dieetevaluering het ’n ongesonde dieetpatroon getoon. Ná vier weke is die deelnemers ewekansig. Die dieetintervensie het ná vier weke tot belangrike voedingsveranderinge by deelnemers gelei, met uremiese toksiene wat onveranderd gebly het. Daar was ’n beduidende vermindering in die liggaamsmassa-indeks (P < 0.006) en middelomtrek (P < 0.001). Feitlik alle dieetinnameveranderlikes is beduidend verlaag en daar was ’n hoë nakoming van die dieet. Serum-totale cholesterol (P < 0.045) en trigliseriedvlakke (P < 0.017) is ook verlaag. Nadat deelnemers ewekansig is na óf die ß-glukaanvoorbiotikum óf die dieet, het die nierfunksie nie beduidend verander nie. Daar was egter ’n beduidende verlaging in uremiese toksiene in vrye IxS in week 8 (P = 0.003) en week 14 (P < 0.001), totale en vrye pCG (P < 0.001 en P < 0.001, onderskeidelik) en vrye pCS (P = 0.006) in week 14. Daar was geen beduidende veranderings in dieetinname, kliniese simptome of antropometrie tydens die studie nie. Die dermmikrobioom het getoon dat twee enterotipes voorgekom het, naamlik die Bacteroides 2- en Prevotella-enterotipe. Die interindividuele Bray-Curtis-afstand (ß-diversiteit) was beduidend hoër by die kontrolegroep as by die intervensiegroep, met basislyn (P < 0.0001), week 8 (P < 0.0001) en week 14 (P = 0.02). Daar was geen verskille in relatiewe oorvloed van genera tussen groepe nie. Die oortolligheidsontleding het getoon dat ’n paar faktore die dermmikrobioom beduidend beïnvloed het: dit het trigliseriedvlakke (P < 0.001), die oorsaak van nierversaking (P < 0.001), geslag (P < 0.001), liggaamsmassa-indeks (P = 0.002), hoëdigtheid-lipoproteïen (P < 0.001) en die prebiotika intervensie (P = 0.002) ingesluit. Gevolgtrekking: Hoewel vier weke van die dieet voor ewekansiging tot ’n paar voedingsveranderings by deelnemers gelei het, het dit nie ander uitkomste van die studie geraak nie. Nadat die deelnemers ewekansig is, het dit nie nierfunksie beduidend geraak nie, terwyl dit uremiese toksiene en die dermmikrobioom volgens die RDA-ontleding beduidend verminder het. Die ß-glukaanprebiotikum het dus ’n paar voordelige uitwerkings op uitkomste by CNS-deelnemers gehad. Stellenbosch University https://scholar.sun.ac.za

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