Clinical effectiveness of adding probiotics to a low FODMAP diet: Randomized double-blind placebo-controlled study

Table 1 Content of low fermentable oligo, di- and monosaccharides and polyols diet recommended for patients

Energy	1600-2000 kcal/d
Protein	75 -90 g/d
Fat	75-85 g/d
Carbohydrate	186-240 g/d
Starch	120-25 g/d
Sugars	50 -75 g/d
Non-starch polysaccharide	13–16 g/d
Total FODMAPs1	9.0-9.6 g/d
Fructans	2.5-3.5 g/d
GOS	0.8-1.4 g/d
Lactose	4.3-4.5 g/d
Total fructose	12.7-5.9 g/d
Excess fructose	1.9-2.0 g/d
Sorbitol	0.3-0.5 g/d
Mannitol	0.1 -0.2 g/d

¹Total fermentable oligo, di- and monosaccharides and polyols (FODMAPs) are calculated as the sum of individual carbohydrates including excess fructose (not total fructose). Data are mean total and individual FODMAPs (g/d), energy (kcal/d) and nutrient intake (g/d). FODMAPs: Fermentable oligo, di- and monosaccharides and polyols; GOS: Galacto-oligosaccharides.

Table 2 Patients’ demographic characteristics, comorbidities and treatments they received

	Total, n = 85	Group 1, n = 43	Group 2, n = 42	P value
Age (mean ± SD)	43.6 ± 13.0	43.6 ± 12.2	43.6 ± 14.0	0.888
Gender, n (%)
Female	62 (72.9)	33 (76.7)	29 (69.0)	0.425
Male	23 (27.1)	10 (23.3)	13 (31.0)
Employment status, n (%)
No	49 (57.6)	25 (58.1)	24 (57.1)	0.926
Yes	36 (42.4)	18 (41.9)	18 (42.9)
Comorbid diseases
Hashimoto’s thyroiditis, n (%)
No	67 (78.8)	36 (83.7)	31 (73.8)	0.263
Yes	18 (21.2)	7 (16.3)	11 (26.2)
Allergic asthma, n (%)
No	77 (90.6)	36 (83.7)	41 (97.6)	0.058
Yes	8 (9.4)	7 (16.3)	1 (2.4)
Hypertension, n (%)
No	72 (84.7)	38 (88.4)	34 (81.0)	0.342
Yes	13 (15.3)	5 (11.6)	8 (19.0)
Gastritis, n (%)
No	77 (90.6)	37 (86.0)	40 (95.2)	0.265
Yes	8 (9.4)	6 (14.0)	2 (4.8)
Hyperlipidemia, n (%)
No	78 (91.8)	40 (93.0)	38 (90.5)	0.713
Yes	7 (8.2)	3 (7.0)	4 (9.5)
Depression, n (%)
No	80 (94.1)	41 (95.3)	39 (92.9)	0.676
Yes	5 (5.9)	2 (4.7)	3 (7.1)
Comorbidity, n (%)
No	26 (30.6)	12 (27.9)	14 (33.3)	0.587
Yes	59 (69.4)	31 (72.1)	28 (66.7)
Abdominal surgery, n (%)
No	50 (58.8)	24 (55.8)	26 (61.9)	0.568
Yes	35 (41.2)	19 (44.2)	16 (38.1)
Drug use
Systematic drug use, n (%)
No	28 (32.9)	14 (32.6)	14 (33.3)	0.939
Yes	57 (67.1)	29 (67.4)	28 (66.7)
PPI use, n (%)
No	67 (78.8)	32 (74.4)	35 (83.3)	0.315
Yes	18 (21.2)	11 (25.6)	7 (16.7)
Psychiatric drug use, n (%)
No	71 (83.5)	34 (79.1)	37 (88.1)	0.262
Yes	14 (16.5)	9 (20.9)	5 (11.9)
CCB use, n (%)
No	69 (81.2)	36 (83.7)	33 (78.6)	0.544
Yes	16 (18.8)	7 (16.3)	9 (21.4)
Beta-blocker use, n (%)
No	75 (88.2)	38 (88.4)	37 (88.1)	> 0.999
Yes	10 (11.8)	5 (11.6)	5 (11.9)

Group 1: Low fermentable oligo, di- and monosaccharides and polyol diet + probiotic; Group 2: Low fermentable oligo, di- and monosaccharides and polyol diet + placebo. PPI: Proton pump inhibitor; CCB: Calcium canal blocker; SD: Standard deviation.

Table 3 Irritable bowel syndrome sub-type breakdown by groups

	Total, n = 85	Group 1, n = 43	Group 2, n = 42	P value
IBS subtype, n (%)
Constipation	43 (50.6)	23 (53.5)	20 (47.6)	0.415
Diarrhea	23 (27.1)	9 (20.9)	14 (33.3)
Mixed	19 (22.4)	11 (25.6)	8 (19.0)

Group 1: Low fermentable oligo, di- and monosaccharides and polyol diet + probiotic; Group 2: Low fermentable oligo, di- and monosaccharides and polyol diet + placebo. IBS: Irritable bowel syndrome.

Table 4 Comparison of visual analogue scale and irritable bowel syndrome symptom severity scale scores before and after treatment

		Group 1			Group 2
	Before treatment	After treatment	P value	Before treatment	After treatment	P value	P’ value
	mean ± SD	mean ± SD		mean ± SD	mean ± SD
VAS	4.6 ± 2.7	2.0 ± 1.9	< 0.001	4.7 ± 2.7	1.8 ± 2.0	< 0.001	0.754
IBS-SSS	310.0 ± 78.4	172.0 ± 93.0	< 0.001	317.0 ± 87.5	175.0 ± 97.7	< 0.001	0.610
Pain severity	49.4 ± 24.1	24.4 ± 20.8	< 0.001	46.4 ± 23.1	22.6 ± 19.8	< 0.001	0.616
Abdominal pain severity	52.9 ± 23.9	26.7 ± 21.4	< 0.001	53.6 ± 25.0	28.6 ± 23.1	< 0.001	0.843
Abdominal distention severity	65.1 ± 25.1	34.3 ± 25.0	< 0.001	68.5 ± 23.5	33.9 ± 24.0	< 0.001	0.660
Satisfaction with intestinal habits	70.9 ± 24.9	41.6 ± 33.3	< 0.001	73.5 ± 27.2	43.4 ± 31.6	< 0.001	0.559
IBS quality of life	74.8 ± 22.1	44.6 ± 26.1	< 0.001	75.0 ± 22.4	46.5 ± 23.3	< 0.001	0.957

P’: Comparison between both groups before treatment. Group 1: Low fermentable oligo, di- and monosaccharides and polyols (FODMAP) diet + probiotic, Group 2: low fermentable oligo, di- and monosaccharides and polyols diet + placebo. VAS: Visual analogue scale; IBS-SSS: Irritable bowel syndrome symptom severity scale; IBS: Irritable bowel syndrome; SD: Standard deviation.

Table 5 Comparison of the change in visual analogue scale and irritable bowel syndrome symptom severity scale scores in both groups before and after treatment

Parameters	Total, n = 85	Group 1, n = 43	Group 2, n = 42	P value
VAS [Median (min-max)]	-50.0 [(-100.0)-40.0]	-50.0 [(-100.0)-0.0]	-58.3 [(-100.0)-40.0]	0.778
IBS-SSS[Median (min-max)]	-47.3 [(-100.0)-30.3)]	-43.5 [(-93.0)-0.0)]	-50.0 [(-100.0)-30.3)	0.871
Pain severity	-50.0 [(-100.0)-50.0]	-50.0 [(-100.0)-0.0]	-50.0 [(-100.0)-50.0]	0.799
Abdominal pain severity	-50.0 [(-100.0)-50.0]	-50.0 [(-100.0)-0.0]	-50.0 [(-100.0)-50.0]	0.857
Abdominal distention severity	-50.0 [(-100.0)-0.0]	-50.0 [(-100.0)-0.0]	-50.0 [(-100.0)-0.0]	0.561
Satisfaction with intestinal habits	-50.0 [(-100.0)-203.0]	-50.0 [(-100.0)-100.0]	-50.0 [(-100.0)-203.0]	0.953
IBS quality of life	-50.0 [(-100.0)-51.5]	-50.0 [(-100.0)-0.0]	-50.0 [(-100.0)-51.5]	0.960

Group 1: Low fermentable oligo, di- and monosaccharides and polyols (FODMAP) diet + probiotic, Group 2: low fermentable oligo, di- and monosaccharides and polyols diet + placebo. VAS: Visual analogue scale; IBS-SSS: Irritable bowel syndrome symptom severity scale; IBS: Irritable bowel syndrome.

Table 6 Irritable bowel syndrome symptom severity scale scores before and after treatment

	After treatment	Before treatment, n (%)			Kappa	P value
		Mild	Moderate	Severe
All patients	Asymptomatic	3 (50.0)	2 (6.5)	4 (8.3)	0.021	0.648
	Mild	3 (50.0)	22 (71.0)	17 (35.4)
	Moderate	0 (0)	6 (19.4)	17 (35.4)
	Severe	0 (0)	1 (3.2)	10 (20.8)
Group 1	Asymptomatic	2 (66.7)	1 (6.7)	2 (8.0)	0.013	0.840
	Mild	1 (33.3)	11 (73.3)	9 (36.0)
	Moderate	0 (0)	3 (20.0)	9 (36.0)
	Severe	0 (0)	0 (0)	5 (20.0)
Group 2	Asymptomatic	1 (33.3)	1 (6.2)	2 (8.7)	0.031	0.649
	Mild	2 (66.7)	11 (68.8)	8 (34.8)
	Moderate	0 (0)	3 (18.8)	8 (34.8)
	Severe	0 (0)	1 (6.2)	5 (21.7)

Group 1: Low fermentable oligo, di- and monosaccharides and polyols (FODMAP) diet + probiotic, Group 2: low fermentable oligo, di- and monosaccharides and polyols diet + placebo.

Table 7 Comparison of stool changes in groups before and after treatment according to the Bristol stool scale

After treatment		Before treatment			Kappa	P value
		Type 1, 2	Type 3, 4	Type 5-7
All patients	Type 1, 2	12 (35.3)	2 (9.1)	2 (6.9)	0.175	0.006
	Type 3, 4	18 (52.9)	16 (72.7)	19 (65.5)
	Type 5-7	4 (11.8)	4 (18.2)	8 (27.6)
Group 1	Type 1, 2	4 (23.5)	2 (14.3)	1 (8.3)	0.061	0.448
	Type 3, 4	12 (70.6)	10 (71.4)	9 (75.0)
	Type 5-7	1 (5.9)	2 (14.3)	2 (16.7)
Group 2	Type 1, 2	8 (47.1)	0 (0)	1 (5.9)	0.26	0.005
	Type 3, 4	6 (35.3)	6 (75.0)	10 (58.8)
	Type 5-7	3 (17.6)	2 (25.0)	6 (35.3)

Group 1: Low fermentable oligo, di- and monosaccharides and polyols (FODMAP) diet + probiotic, Group 2: low fermentable oligo, di- and monosaccharides and polyols diet + placebo.

Table 8 The relationship between adherence to diet and changes in visual analogue scale and irritable bowel syndrome symptom severity scale scores

Scores	Group 1; adherence to diet		Group 2; adherence to diet
	r	P value	r	P value
VAS	0.226	0.145	0.425	0.005
IBS-SSS	0.226	0.144	0.434	0.004
Pain severity	0.233	0.133	0.253	0.106
Abdominal pain severity	0.298	0.052	0.287	0.065
Abdominal distention severity	0.001	0.995	0.298	0.055
Satisfaction with intestinal habits	0.092	0.557	0.328	0.034
IBS quality of life	0.264	0.088	0.390	0.011

Group 1: Low fermentable oligo, di- and monosaccharides and polyols (FODMAP) diet + probiotic, Group 2: Low fermentable oligo, di- and monosaccharides and polyols diet + placebo. The discrepancy between the initial and final values of the evaluated scores (visual analogue scale, irritable bowel syndrome, etc.) was proportioned to the initial value to create a new variable called “percentage change from baseline” ((last value - initial value)/initial value). The correlation of this variable with dietary compliance in two different groups was investigated. The relationship between the improvement in other scores (numerical) and the diet compliance score (numerical) was investigated. The “r” values we received provide us with knowledge about the relationship’s course and power. VAS: Visual analogue scale; IBS-SSS: Irritable bowel syndrome symptom severity; IBS: Irritable bowel syndrome.