Bifidobacterium quadruple viable tablets can improve saliva and reduce adverse effects in patients treated with Helicobacter pylori eradication

In August 2021, the team of Professor Zhou Liya of Peking University Third Hospital published in the journal Helicobacter the effect of Hp eradication therapy combined with probiotics (Bifidobacterium quadruple live bacteria) on the microbiome of the stomach in young people[1].

The results of this study found that Hp infection significantly reduced the diversity of gastric mucosa and gastric flora, and eradication therapy with bismuth standard quadruple regimen (PPI+ bismuth + amoxicillin + clarithromycin) could restore the diversity of gastric flora to a certain extent, but it could not completely recover to the uninfected state
within 2 months.
The addition of Bifidobacterium quadruple viable tablets at the same time as eradication therapy is more helpful to restore the gastric microecology to the state of Hp uninfected patients, and can increase the abundance of potential probiotics in the gastric mucosa to a certain extent
.
This study has great clinical practice guiding significance, which has aroused the attention and thinking
of the academic community.
In 2022, Professor Zhou Liya, head of the Helicobacter pylori group of the Gastroenterology Branch of the Chinese Medical Association, and all the experts of the group, formulated the "Sixth National Consensus Report on the Treatment of Helicobacter Pylori Infection (Non-Eradication Part)", which also explained that "Hp infection reduces the abundance and diversity of gastric microbial population" and "eradication of Hp changes the diversity and structure of intestinal microbial population in the short term"
for the part of Hp infection and intestinal microecology 。 Another recent study showed that taking Bifidobacterium quadruple tablets can improve the status of saliva, gastric and intestinal flora in patients treated with Helicobacter pylori eradication, and reduce the occurrence
of adverse reactions of eradication therapy bismuth quadruple regimen.

Helicobacter pylori (H.
pylori) is one of the most widespread infections worldwide, with a prevalence of approximately 50% of the global population [2].

Helicobacter pylori infection may cause chronic gastritis and increase the risk
of peptic ulcer, gastric cancer, and mucosa-associated lymphoid tissue lymphoma.
Up to now, bismuth-containing quadruple therapy has become an internationally recognized first-line regimen for the treatment of Helicobacter pylori [3], but further studies have found that the use of quadruple therapy can lead to gastrointestinal adverse reactions and short-term disturbances of the intestinal flora in patients [4, 5].

Bifidobacterium quadruple viable tablets are currently widely used to regulate intestinal dysbacteriosis and treat diarrhea, constipation, indigestion and other diseases
.
Studies have confirmed that the combination of probiotics can reduce the gastrointestinal adverse reactions caused by bismuth quadruple [6, 7], and help the reconstruction of beneficial bacterial profiles in the gastric and intestinal flora after bismuth quadruple drug treatment [8].

Therefore, the effect of bifidobacterium quadruple viable tablets on the gastrointestinal flora of patients after Helicobacter pylori eradication is of far-reaching significance and deserves attention
.

Professor Lv Nonghua of the First Affiliated Hospital of Nanchang University led a two-year, eight-month multi-center, randomized, double-blind, placebo-controlled study led by seven tertiary hospitals across China, including Xi'an Central Hospital, the First Affiliated Hospital of Shanxi Medical University, the Fifth Affiliated Hospital of Zhengzhou University, the First People's Hospital of Yunnan Province, the First Hospital of Nanjing and the First Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine, and Frontiers in Immunology in November 2022 (IF:8.
786) published a research paper
titled "Probiotics modulate gastrointestinal microbiota after Helicobacter pylori eradication: A multicenter randomized double-blind placebo-controlled trial.
" 。 To further clarify the efficacy and safety of Bifidobacterium quadruple viable tablets (Siliankang) combined with 14-day bismuth-containing quadruple therapy for eradication of Helicobacter pylori, and its effect
on changes in gastrointestinal flora.
Studies included adults (aged 18 to 65 years)
diagnosed with chronic gastritis who tested positive for Helicobacter pylori.
Eligible patients were randomized to Bifidobacterium quadruple live tablets or placebo in
a 1:1 ratio.
Patients in both groups received 14 days of bismuth-containing quadruple therapy (esomeprazole 20 mg, amoxicillin 1000 mg, furazolidone 100 mg, potassium bismuth citrate 220 mg, morning and evening), combined with bifidobacterium quadruple live bacteria tablets (Si Liankang, Hangzhou Yuanda Biopharmaceutical Co.
, Ltd.
, Hangzhou, China) or placebo (9 tablets/time, taken at noon), the course of treatment was 4 weeks
。 It was assessed
at baseline screening (T1), at the end of 14-day eradication therapy (T2), at the end of bifidobacterium quadruple live tablets/placebo (T3), at 8 weeks post-eradication (T4) and at 24 weeks post-eradication (T5).
The results showed that the incidence of gastrointestinal adverse reactions in the bifidobacterium quadruple viable tablets group was lower than that in the placebo group (23.
6% vs 37.
7%, P = 0.
016).

In addition to this, after eradication, the structure of the intestinal flora changed drastically, with Proteobacteria phylum replacing the symbiotic Firmicutes and Bacteroides phylums, which gradually recovered
after two weeks.
Supplementation with Bifidobacterium quadruple viable tablets (Siliancom) neutralizes the reduction of Bacteroides enteroenteric phylum caused by eradication drugs, smooths the fluctuation of gastric flora, and inhibits the growth of oral pathogenic bacteria (Figure 1).

Figure 1

1.
Take Bifidobacterium quadruple viable tablets to reduce adverse reactions after Helicobacter pylori eradication

Compared with the placebo group, the overall incidence of gastrointestinal adverse reactions was significantly lower in the Bifidobacterium quadruple viable tablets group (23.
62% vs 37.
7%, P = 0.
016), and the incidence of nausea and vomiting in the placebo group was higher than in the Bifidobacterium quadruple viable tablets group (24.
59% vs 13.
39%, P = 0.
024) (Figure 2).

Figure 2

2.
Taking Bifidobacterium quadruple viable tablets can alleviate the intestinal flora disorder after Helicobacter pylori eradication

By analysing 597 stool samples from two groups of patients collected during five visits (65 in the Bifidobacterium quadruple viable tablet group and 61 in the placebo group), there was no statistically significant difference between the two groups, and the alpha diversity index, including Chao1 and Shannon, was significantly reduced
at week 2 (T2) compared with baseline (T1).
These indices rapidly rose to baseline levels at week 4 (T3) and remained stable until 1 year (T5) (Figure 3).

At the phylum level, the intestinal flora before treatment was dominated by Bacteroides and Firmicutes, and after discontinuation of eradication drugs, the relative abundance of Proteobacteria phylum increased significantly and became the dominant phylum, while the relative abundance of Bacteroides, Firmicutes and Actinomycetes was significantly reduced, and from T3 to T5, the dominance of Proteobacteria phylum was replaced by Bacteroides and Firmicutes and returned to the baseline level (Figure 4).

Among them, the proportion of patients with Proteobacteria as the dominant phylum was higher in the placebo group, and the beta diversity in T1-T3 was more
different.
Figure 3

Figure 4

3.
Taking Bifidobacterium quadruple viable tablets can reduce the fluctuation of gastric flora after Helicobacter pylori eradication

A total of 68 gastric mucosal samples were analyzed
in 34 patients (18 in the bifidobacterium quadruple viable tablet group and 16 in the placebo group) at two time nodes before and 8 weeks after Helicobacter pylori eradication treatment.
Unlike the intestinal flora, in patients with Helicobacter pylori infection, the gastric flora is dominated by Proteobacteria, followed by Firmicutes and Bacteroides (Figure 5).

The Chao1 and Shannon indices showed that alpha diversity increased in the placebo group after Helicobacter pylori eradication while there was no significant change in the Bifidobacterium quadruple viable tablet group (Figure 6).

Suggests that supplementation with Bifidobacterium quadruple viable tablets (Siliancom) can mitigate gastric microbiota changes
caused by Helicobacter pylori eradication.
Figure 5

Figure 6

4.
Taking Bifidobacterium quadruple viable tablets can inhibit the growth of some pathogenic bacteria in the oral cavity after Helicobacter pylori is eradicated

Through the analysis of a total of 112 saliva samples in 56 patients (27 in the bifidobacterium quadruple viable tablet group and 29 in the placebo group) at two time points before eradication and 8 weeks after eradication treatment, it was found that the administration of Bifidobacterium quadruple viable tablets (Siliankan) could inhibit the increase of pathogenic bacteria (such as Porphyromonas spp.
, Ciliates spp.
, Actinomycetes, and Prevos) in oral saliva compared with the placebo group (Figure 7).

Figure 7

Summary

There is growing evidence that bismuth quadruple therapy to eradicate Helicobacter pylori infection results in short-term impairment
of gut microbiota homeostasis.
This study showed that taking Bifidobacterium quadruple viable tablets (Siliankang) reduced the incidence
of gastrointestinal adverse reactions.
After eradication of Helicobacter pylori, the composition of the saliva, stomach, and gut microbiota changed significantly, and the gut flora returned to baseline two weeks after stopping antibiotics
.
By taking Bifidobacterium quadruple viable tablets (Siliankang) treatment, the disorder of microbial flora can be alleviated
.
This provides a new clinical application direction and ideas
for the further optimization of Helicobacter pylori treatment regimen and the reduction of side effects.