Pre-, Pro-, and Synbiotics: Do They Have a Role in Reducing Uremic Toxins? A Systematic Review and Meta-Analysis

Table 2

Published studies on the effectiveness of probiotics on reducing indoxyl sulphate and p-cresyl sulphate.

Author; (year)	Study; design	Patients	Supplement total dose/day (CFU or g) number of doses/day	Duration	Analysis method	Main results (preintervention and postintervention (mean difference))	Comments	Grade benefit
Ling et al.,; (1994) [25]		𝑛=33 healthy female	Lactobacillus rhamnosus GG 1×10^11 administered in yogurt	0–4 wks	Heat and acid deproteinisation, HPLC, FS	ΔUrinary PC mg/24 hr	(i) Subgroup from a larger study	Moderate
	Placebo-controlled non-randomised experimental trial	𝑛=22 treatment				(within group, wk 0–4)	(ii) 2 week runout period levels increased towards baseline levels 41.5 mg/24 hr
		𝑛=11 placebo	1 dose/day			Tx grp: 45.0–35.5 (−9.5) (<0.05)	(iii) Both groups were also given 9 g fibre from aleuronic layer of whole-grain rye daily	PC+
						Placebo: 46.5–43.1 (−3.4) (ns)	(iv) 3 day food records were analysed for macro nutrients and fibre questionnaire for total fibre intake. No significant difference between groups was reported
Tohyama et al., (1981); [26]		𝑛=7 healthy (all male)	Lactobacillus casei 90241; 1×10^10 administered in milk	0–3 wk control; 4–9 wk; intervention	Heat and acid deproteinisation, GC, FID	ΔUrinary (percentage of reduction (±SD))	(i) Urine was analysed at different times of the day between baseline and post	Very Low
	Interrupted time series without a parallel control group					(within group, wk 4–9)	(ii) Included rat study which showed significant reductions also
						PC − 42.6 (±33.7) (<0.05)	(iii) Strong correlation between fecal tryptophanase activity and urinary IS (𝑟=0.93)
			1 dose/day			IS − 29.3 (±15.9) (<0.05)	(iv) 2 week run-out period concentrations returned to initial levels post feeding—data not shown	PC+
							(v) No dietary restrictions	IS+
Fujiwara et al., (2001); [27]	Case series	𝑛=8 healthy	Lactobacillus gasseri SBT2055SR-lyophilized 1×10^11 administrated in milk; 1 dose/day	0-1 wk	Deprotinisation method was not disclosed, HPLC, UV-VIS	ΔFecal mg/g; (wk 0-1); PC 0.064–0.022* (− 0.045) (0.01); Indole (not reported) (ns)	(i) Subgroup of another study; (ii) Decreased staphylococcus 𝑃<0.05; (iii) By 5 day run-out PC levels returned to baseline*; (iv) Usual diet with restriction on fermented milk, pickles, and natto	Low; PC+; IS−
Takayama et al., (2003); [33]	Nonrandomised-placebo controlled experimental trial	𝑛=22 hemodialysis (𝑛=14 male)	Probiotic: Bifidobacterium longum strain JCM008 administered in gastroresistant capsules 3 × 10^9	0–5 wks	Deproteinization (not disclosed); Reverse-phase HPLC, FS	ΔSerum IS (mg/L); (within group, wk 0−5)	(i) Placebo has different dose and strain	Low
		𝑛=11 treatment	Placebo: Bifidobacterium (powder form) 2 × 10^7			Tx group: 49.0–35.0 (−14.0) (<0.005)	(ii) 2 week runout period levels increased towards baseline levels 44 mg/L	IS+
		𝑛=11 placebo	Dose/day not disclosed			Placebo: 48.0–52.0 (+4.0) (ns)	(iii) No monitoring of diet
Taki et al., (2005); [34]		𝑛=27 hemodialysis (𝑛=14 male)	Bifidobacterium longum	0–12 wks	Not disclosed	ΔSerum IS (mg/L)	(i) Strain not disclosed	Very low
			0–4 wks: 3 × 10^9			(wk 0–4); 35.1–31.0 (−4.1) (<0.01)	(ii) Analysis methods not described
	Case series		4–8 wks: 6 × 10^9; 8–12 wk: 12 × 10^9			(wk 0–8); 35.1–31.7 (−3.4) (<0.05)	(iii) No dose response effect
			Administered in gastroresistant capsule			(wk 0–12); 35.1–31.9 (−3.2) (<0.05)	(iv) No runout period
			Dose/day not disclosed				(v) Monitoring of diet (not disclosed)	IS+
Hida et al., (1996) [35]		𝑛=20 hemodialysis (𝑛=8 male)	Bifidobacterium infantis, Lactobacillus acidophilus, Enterococcus faecalis 2 × 10^8of each strain administered in a capsule	0–4 wks	Plasma: reverse-Phase HPLC, UV detection	ΔPlasma (mg/L); (wk 0–4)	(i) Strain not disclosed	Very low
	Case series				Fecal: steam distilled, GC, FID	IS 45.2–31.1 (−14.1) (<0.01)	(ii) Fecal analysis included 10 patients only from 0–2 week	IS+
						PC 17.8–18.3*(+0.5) (ns)	(iii) Decreased enterobacteria 𝑃<0.05	PC+ (fecal)
			2 dose/day			ΔFecal (mg/g)  (wk 0–4); PC 102.0–70.0* (−32.0 ) (<0.01)	(iv) No runout period	PC− (serum)
						Indole 45.0–32.0* (−13.0) (<0.05)	(v) No monitoring of diet