Multistrain probiotics alleviate gastrointestinal symptoms during bismuth quadruple therapy for Helicobacter pylori infection

Table 1 Baseline characteristics of study subjects, n (%)/mean ± SD

Variables	Total population (n = 174)	Intervention group (n = 89)	Placebo-controlled group (n = 85)	χ²/t	P value
Sex				2.271	0.132
Male	63 (36.2)	37 (41.6)	26 (30.6)
Female	111 (63.8)	52 (58.4)	59 (69.4)
Age, years				2.987	0.394
≤ 29	49 (28.2)	26 (29.2)	23 (27.1)
30-39	59 (33.9)	25 (28.1)	34 (40.0)
40-49	35 (20.1)	20 (22.5)	15 (17.6)
≥ 50	31 (17.8)	18 (20.2)	13 (15.3)
BMI (kg/m2)				0.081	0.960
< 18.5	12 (6.9)	6 (6.7)	6 (7.1)
18.5-23.9	107 (61.5)	54 (60.7)	53 (62.4)
≥ 24.0	55 (31.6)	29 (32.6)	26 (30.6)
Ethnic group				0.528	0.468
Han	164 (94.3)	85 (95.5)	79 (92.9)
Other	10 (5.7)	4 (4.5)	6 (7.1)
Household characteristics				0.169	0.681
Urban	101 (58.0)	53 (59.6)	48 (56.5)
Rural	73 (42.0)	36 (40.4)	37 (43.5)
Marital status				1.316	0.518
Unmarried	45 (25.9)	25 (28.1)	20 (23.5)
Married	118 (67.8)	60 (67.4)	58 (68.2)
Other	11 (6.3)	4 (4.5)	7 (8.2)
Education				0.109	0.991
Junior high school and below	21 (12.1)	11 (12.4)	10 (11.8)
High school	26 (14.9)	13 (14.6)	13 (15.3)
College/vocational university	28 (16.1)	15 (16.9)	13 (15.3)
Bachelor's degree and above	99 (56.9)	50 (56.1)	49 (57.6)
Vocation				0.708	0.702
Working	101 (58.0)	50 (56.2)	51 (60.0)
Unemployed/household	25 (14.4)	12 (13.5)	13 (15.3)
Other	48 (27.6)	27 (30.3)	21 (24.7)
Per capita monthly income (CNY)				2.358	0.670
< 4000	46 (26.4)	23 (25.8)	23 (27.1)
4001-6000	33 (19.0)	20 (22.5)	13 (15.3)
6001-8000	31 (17.8)	17 (19.1)	14 (16.5)
8001-10000	19 (10.9)	8 (9.0)	11 (12.9)
> 10000	45 (25.9)	21 (23.6)	24 (28.2)
Smoking				0.009	0.923
Yes	16 (9.2)	8 (9.0)	8 (9.4)
Drinking				0.071	0.789
Yes	76 (43.7)	38 (42.7)	38 (44.7)
Reason for visit				1.446	0.485
Digestive discomfort	109 (62.6)	52 (58.4)	57 (67.1)
Chronic gastritis	52 (29.9)	30 (33.7)	22 (25.9)
Ulcers	13 (7.5)	7 (7.9)	6 (7.0)
13C/14C expiratory value	22.23 ± 16.17	21.94 ± 15.48	23.80 ± 16.93	0.739	0.461

BMI: Body mass index; CNY: China yuan.

Table 2 Gastrointestinal Symptom Rating Scale total and dimensional scores of study participants before and after intervention, mean ± SD

Variables	Intervention group (n = 89)	Placebo-controlled group (n = 85)	Z	P value
Baseline
Reflux syndrome	3.87 ± 2.13	3.09 ± 1.43	-2.606	0.009b
Abdominal pain syndrome	2.76 ± 2.91	2.44 ± 2.94	-0.999	0.318
Dyspepsia	5.78 ± 4.61	4.79 ± 3.71	-1.232	0.218
Diarrhea	3.76 ± 3.78	3.13 ± 3.02	-0.876	0.381
Constipation	2.75 ± 3.50	2.56 ± 3.34	-0.370	0.711
GSRS total score	18.67 ± 12.75	16.25 ± 10.43	-1.094	0.274
After 4 weeks of intervention
Reflux syndrome	0.55 ± 1.11	0.42 ± 1.43	-0.896	0.370
Abdominal pain syndrome	0.60 ± 0.98	0.68 ± 1.51	-1.283	0.196
Dyspepsia	1.71 ± 1.94	2.05 ± 2.86	-0.362	0.717
Diarrhea	0.90 ± 1.07	1.44 ± 1.80	-1.396	0.163
Constipation	0.88 ± 1.49	1.32 ± 2.15	-1.027	0.304
GSRS total score	4.64 ± 4.36	5.90 ± 7.05	-0.351	0.726
After 8 weeks of intervention
Reflux syndrome	0.34 ± 1.21	0.33 ± 1.32	-0.044	0.965
Abdominal pain syndrome	0.54 ± 1.13	0.74 ± 1.47	-0.220	0.826
Dyspepsia	1.41 ± 1.81	1.97 ± 2.55	-1.308	0.191
Diarrhea	0.85 ± 1.09	1.12 ± 1.74	-0.009	0.314
Constipation	0.80 ± 1.38	1.05 ± 1.58	-1.027	0.304
GSRS total score	3.94 ± 4.45	5.22 ± 6.26	-1.096	0.273

^bP ≤ 0.01.

Reflux syndrome: Acid reflux, heartburn; Abdominal pain syndrome: Abdominal pain, hunger pain, nausea and vomiting; Dyspepsia: Bowel sounds, bloating, intestinal flatulence, hiccups/belching; Diarrhea syndrome: Diarrhea, loose stools, the feeling of urgency to defecate; Constipation syndrome: Constipation, hardened stools, feeling of incomplete defecation; GSRS total score: The sum of the scores of the 5 dimensions, with higher scores indicating more severe symptoms.

Table 3 Changes in the gastrointestinal symptom scores of the study participants after intervention, mean ± SD

Variables	Intervention group (n = 89)	Placebo-controlled group (n = 85)	Z	P value
GSRS score after 2 weeks of intervention - baseline GSRS score
Reflux syndrome2-0	-3.06 ± 1.50	-2.58 ± 1.26	2.243	0.025a
Abdominal pain syndrome2-0	-1.25 ± 2.11	-1.46 ± 2.68	0.016	0.987
Dyspepsia2-0	-3.00 ± 3.66	-2.58 ± 3.17	0.801	0.423
Diarrhea2-0	-1.70 ± 3.74	-1.87 ± 2.83	-0.831	0.406
Constipation2-0	-1.62 ± 3.08	-1.62 ± 2.93	-0.164	0.870
GSRS total score2-0	-8.63 ± 9.54	-8.11 ± 8.30	0.495	0.620
GSRS score after 4 weeks of intervention - baseline GSRS score
Reflux syndrome4-0	-3.09 ± 1.41	-2.64 ± 1.34	-1.933	0.053
Abdominal pain syndrome4-0	-1.93 ± 2.39	-1.58 ± 2.68	-0.754	0.451
Dyspepsia4-0	-3.89 ± 3.87	-2.45 ± 3.59	-1.813	0.070
Diarrhea4-0	-2.90 ± 3.21	-1.60 ± 2.77	-2.458	0.014a
Constipation4-0	-1.74 ± 2.54	-1.14 ± 2.87	-1.525	0.127
GSRS total score4-0	-13.55 ± 9.26	-9.40 ± 8.46	-2.356	0.018a
GSRS score after 8 weeks of intervention - baseline GSRS score
Reflux syndrome8-0	-3.00 ± 1.41	-2.62 ± 1.64	-1.365	0.172
Abdominal pain syndrome8-0	-2.02 ± 2.32	-1.60 ± 3.04	-1.350	0.177
Dyspepsia8-0	-4.19 ± 3.75	-2.59 ± 3.20	-2.381	0.017a
Diarrhea8-0	-2.98 ± 3.31	-1.83 ± 2.62	-1.846	0.065
Constipation8-0	-1.87 ± 3.02	-1.36 ± 3.00	-1.316	0.188
GSRS total score8-0	-14.06 ± 9.32	-10.00 ± 8.56	-2.279	0.023a

^aP < 0.05.

GSRS total score: The sum of the scores of the 5 dimensions, with higher scores indicating more severe symptoms.

Table 4 Protective effects of probiotic intervention on the occurrence of gastrointestinal symptoms

Variables	Incidence of gastrointestinal reactions after 2 weeks of intervention (%)		Relative risk reduction (%)	Incidence of gastrointestinal reactions after 4 weeks of intervention (%)		Relative risk reduction (%)	Incidence of gastrointestinal reactions after 8 weeks of intervention (%)		Relative risk reduction (%)
	Intervention group (n = 89)	Placebo-controlled group (n = 85)		Intervention group (n = 89)	Placebo-controlled group (n = 85)		Intervention group (n = 89)	Placebo-controlled group (n = 85)
Reflux syndrome	37.8	24.1	0.6	6.8	7.1	4.4	2.9	7.1	59.2
Abdominal pain syndrome	48.8	48.1	0.01	12.9	14.8	12.8	8.7	16.9	48.5
Dyspepsia	74.4	70.9	0.05	34.3	37.9	9.5	26.1	36.6	28.7
Diarrhea	69.5	55.7	0.2	26.8	37.8	29.1	23.3	28.2	13.9
Constipation	39.0	34.2	0.1	18.6	21.6	13.9	13.1	17.0	22.9

Table 5 Comparison of Helicobacter pylori eradication rates in the study population, n (%)

Variables	Intervention group (n = 89)	Placebo-controlled group (n = 85)	χ²	P value
Eradication rate	79 (88.8)	72 (84.7)	0.790	0.430

Table 6 Adherence assessment of the study participants, n (%)

Time points	Good compliance
After 2 weeks of intervention
Intervention group (n = 82)	77 (93.9)
Placebo-controlled group (n = 79)	70 (88.6)
Total population (n = 161)	147 (91.3)
After 4 weeks of intervention
Intervention group (n = 78)	70 (89.7)
Placebo-controlled group (n = 76)	67 (88.2)
Total population (n = 154)	137 (89.0)