In the present study including PPI-users as the subjects, the administration of a probiotic strain, LG21, was strongly suggested to improve the upper GI tract-related symptoms that had persisted in spite of the use of a PPI every day, whereas interpretation of the result takes caution because the present study lacked a control group. In a previous study on H. pylori
-infected individuals, on the other hand, the efficiency of LG21 for the treatment of stomach-related symptoms was demonstrated by a double-blinded randomized controlled trial [10
]. In this study, LG21 was revealed to be effective for suppressing the symptoms of postprandial distress syndrome such as fullness and bloating. While it still remains unclear how LG21 improved these symptoms, a mechanism other than gastric acid suppression is suggested because LG21 could still alleviate the symptoms in the patients who had been treated by a PPI in everyday clinical practice. The stomach-related biomarker values showed some change in association with the improvement of the symptoms by LG21 treatment. Therefore we investigated the relationship between the symptoms and these gastric biomarkers to elucidate the reasons for such improvement.
In the analysis using both Spearman’s correlation and the multiple regression tests, a significant correlation was found between the PGI level and the symptoms, especially the dysmotility symptom. PGI is predominantly secreted into the gastric lumen by chief cells and is detectable in the serum. PGs are then degraded auto-catalytically in the acidic environment to form a number of active pepsins that in turn initiate the digestion of ingested proteins in the stomach [11
]. Therefore if the PGI level was directly involved in the occurrence of the symptoms, an increase in the PGI/pepsin level and thus the acceleration of the digestion of food proteins in the stomach might be one of the reasons to explain the association between the higher PGI level and the amelioration of symptoms in our patients, especially in the case of dysmotility symptoms.
Another possible reason might be that a common factor is involved in both the regulation of the serum PGI level and the degree of the symptoms. Long-term therapy with PPI is known to be associated with increased levels of PGI, an effect probably mediated by the associated hyper-gastrinemia [12
]. In the present study, all of the subjects had been treated with a PPI for several years or more and many of them had already exhibited a high level of both gastrin and PGI at the start of the LG21 treatment. However, LG21 treatment exerted no change on the gastrin level whereas this treatment tended to further increase the PGI level. Therefore, it is unlikely that gastrin is a common factor that improves the symptoms and increases the level of PGI. Uchida et al.
] reported that yogurt containing LG21 significantly increased the prostaglandin E2
generation in the gastric mucosa in rats. Prostaglandins, such as prostaglandin E2
and prostaglandin I2
, are known to exert gastro-protective effect by increasing the gastric mucosal blood flow or bicarbonate secretion. Moreover, prostaglandin E2
is reported to stimulate chief cells to secrete PGI via the cAMP pathway [14
]. Taken together, these data suggest the possibility that LG21 induced the generation of prostaglandin E2
, which then improved the symptoms via its gastro-protective effects and also increased the PGI level in the stomach in the present study.
Of note was that a strong reverse correlation was found between age and the symptom scores in the present study. The risk of developing gastric atrophy is one of the pathophysiological features of PPI-users [15
]. As all the subjects were chronic PPI-users, the older subjects tended to have used PPI longer and thus had a higher risk of advanced atrophy. Such atrophic gastric mucosa will secrete less amount of gastric acid, and may be insensitive to recognizing the disorders causing stomach-related symptoms. The development of dementia with aging might also have caused a loss in the sensation of the symptoms in the older subjects.