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Probiotic L. Gasseri Strain (LG21) for the Upper Gastrointestinal Tract Acting Through Improvement of Indigenous Microbiota

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Probiotic L. Gasseri Strain (LG21) for the Upper Gastrointestinal Tract Acting Through Improvement of Indigenous Microbiota BMJ Open Gastroenterol: first published as 10.1136/bmjgast-2019-000314 on 12 August 2019. Downloaded from Review Probiotic L. gasseri strain (LG21) for the upper gastrointestinal tract acting through improvement of indigenous microbiota Yasuhiro Koga, 1 Toshihiro Ohtsu,2 Katsunori Kimura,2 Yukio Asami2 To cite: Koga Y, Ohtsu T, ABSTRACT adequate amounts, confers a health benefit Kimura K, et al. Probiotic Objective To describe probiotics including a Lactobacillus on the host’. The International Scientific strain (LG21) for L. gasseri gasseri strain LG21 used for the upper gastrointestinal Association for Probiotics and Prebiotics the upper gastrointestinal tract, which are considered to act through improvement of tract acting through consensus statements recently reported in indigenous microbiota inhabiting there. 3 improvement of indigenous 2014 also retained the main body of these Background and design Because the early definition microbiota. BMJ Open Gastro definitions. of probiotics emphasized their effects on improving 2019;6:e000314. doi:10.1136/ The gut contains a complex and dynamic bmjgast-2019-000314 the intestinal microbial ecology, their effects on the intestinal tract and its immunity have been considered microbial ecosystem with a high density of common general benefits associated with probiotics. bacteria whose cell number can reach as Received 24 May 2019 12 Revised 29 June 2019 This conclusion was also based on a body of successful high as approximately 10 /g faeces, the Accepted 16 July 2019 clinical trials whose endpoints were the prevention or total number of which is thus estimated to be treatment of intestinal diseases. In contrast to intestinal 10-fold larger than the total number of eukary- by copyright. microbiota, our understanding of the role of gastric otic cells in the human body.4 Because the microbiota in human health and physiology remains early definition of probiotics emphasised their poor, as the bacterial load in the stomach is considered effects on improving the intestinal microbial too small to exert a significant effect due to the highly ecology, their effects on the intestinal tract and acidic environment of the human stomach. Therefore, the intervention using probiotics in the stomach is still limited its immunity have been considered common at present.Results:In this article using representative 38 general benefits associated with probiotics. quoted articles, we first describe the gastric microbiota, as This conclusion was also based on a body the indigenous microbiota in the stomach is thought to be of successful clinical trials whose endpoints http://bmjopengastro.bmj.com/ significantly involved in the pathophysiology of this organ, were the prevention or treatment of intestinal since probiotics exert their beneficial effects through diseases, such as infectious diarrhoea, anti- improving the resident microbiota. We then review the microbial-associated diarrhoea, constipation, present status and future prospects of probiotics for the irritable bowel syndrome (IBS), inflammatory treatment of upper gastrointestinal diseases by quoting bowel diseases, necrotising enterocolitis and representative published articles, including our basic and symptomatic abdominal pain. clinical data. By contrast, the size of the gastric microbial Conclusions Probiotics have been demonstrated to suppress Helicobacter pylori in the stomach, and are also mass, in which probiotic bacteria are consid- expected to improve functional dyspepsia through the ered to exert their beneficial effects, has been correction of dysbiotic gastric microbiota. thought to be very small because of the high © Author(s) (or their on September 28, 2021 by guest. Protected employer(s)) 2019. Re-use acidity and frequent peristalsis to the gut permitted under CC BY-NC. No in the stomach. The high acidity due to the commercial re-use. See rights secreted gastric acid kills probiotic bacteria as and permissions. Published INTRODUCTION well as gastric commensal bacteria. Thus the by BMJ. 1 1 In 1989, Fuller defined probiotics as ‘a live application of probiotics to the stomach or Gastroenterology, Tokai proximal small intestine has historically been University School of Medicine, microbial feed supplement that beneficially Isehara City, Japan affects the host animal by improving its intes- considered impractical. However, the Maas- 5 2Food Microbiology Research tinal microbial balance’. This influential defi- tricht 2-2000 Consensus Report first noted Laboratories, Meiji, Hachiouji nition was then followed by the standard defi- the possible role of gastric probiotics in the City, Japan nition presented by the Joint (Food and Agri- treatment of Helicobacter pylori infection in Correspondence to culture Organizationns of the UNs) FAO/ the stomach, as several studies reported that 2 Yasuhiro Koga; WHO Expert Consultation in 2001 : ‘a live some probiotic bacteria exerted an inhibi- jpn. probio1998@ mbr. nifty. com microorganism that, when administered in tory effect on H. pylori in vitro and in vivo. Koga Y, et al. BMJ Open Gastro 2019;6:e000314. doi:10.1136/bmjgast-2019-000314 1 BMJ Open Gastroenterol: first published as 10.1136/bmjgast-2019-000314 on 12 August 2019. Downloaded from Open access Nevertheless, even at present the use of probiotics for relatively small-size population in the GF from subjects the treatment of illness in the upper gastrointestinal (GI) with H. pylori infection. tract, including the oesophagus, stomach and duodenum, remains limited and far rather than their application in Difference in the microbial community structure among GF, the colon. saliva and faeces In this article, we first describe the gastric microbiota, Tsuda et al9 compared three bacterial communities in the as the indigenous microbiota in the stomach is thought oral cavity, stomach and colon along the alimentary tract to be significantly involved in the pathophysiology of using 45 subjects, including 18 patients taking proton- this organ, since probiotics exert their beneficial effects pump inhibitors (PPIs). Stimulated saliva, GF and faeces through improving the resident microbiota. We then were obtained from each subject for the microbiota anal- review the present status and future prospects of probi- ysis using 16S rRNA gene sequencing method. A total of otics for the treatment of upper GI diseases by quoting 3000 high-quality reads for the sequence analysis were representative published articles, including our basic and randomly selected from each sample and used for the clinical data. subsequent bioinformatic analyses. No marked difference in the degree of bacterial species richness (α-diversity) was found among salivary, GF and GASTRIC MICROBIOTA faecal microbiotas. The average numbers of operational Gastric microbiota analyses by 16S rRNA gene profiling taxonomic units, that is, the number of bacterial species, using high-throughput DNA sequencing all ranged from 120 to 140/mL or g in the three micro- So far, in reports of gastric microbiota analyses using biota samples, indicating that the overall species rich- traditional culturing methods, the bacterial count was so ness was so similar among these microbiotas, regardless small (~103 colony-forming unit (CFU)/mL gastric fluid of differences in their habitats. In contrast, the log CFU (GF)) that it was almost impossible to accurately deter- bacterial counts (median) quantified by real-time PCR mine an overview of the bacterial community structure were 8.7/mL, 7.8/mL and 10.5/g in the saliva, GF and in the stomach.6 faeces, respectively, meaning that the total bacterial count In 2006, Bik et al7 performed a 16S rRNA gene anal- was sensitive to different environmental factors such as ysis using 1833 sequences obtained from 23 human the pH, oxygen concentration and nutrient availability. by copyright. gastric endoscopic biopsy samples and identified 128 It is also noteworthy that the copy number of bacterial bacterial phylotypes. Li et al8 also performed 16S rRNA genome is far higher than the CFU number of bacteria gene profiling using 1223 non-H. pylori sequences from in the GF (107.8/mL vs 102~4/mL), suggesting that more 10 gastric biopsy samples, which were classified into 133 than 99.9% of the GF bacteria are dead and/or viable but phylotypes. In both of those studies regarding the gastric non-culturable. These results suggest that the diversity mucosa-associated microbiota using high-throughput and mass size of GF microbiota might be great enough 16S rDNA sequencing, the results were so similar, to significantly affect the pathophysiology of the stomach although the two studies analysed racially distinct popu- through the metabolites and components of the bacteria. http://bmjopengastro.bmj.com/ lations living in different countries. Both studies found The structure of the whole bacterial community was two predominantly abundant genera—Streptococcus and compared using unique fraction metric (UniFrac) anal- Prevotella—that accounted for approximately half of the yses. Unweighted and weighted UniFrac principal coor- total detected species. In 2015, Tsuda et al9 performed a dinate analyses showed that the salivary and GF samples meta-16S analysis of the gastric luminal microbiota from aggregated to form a common cluster different from the Japanese subjects with far greater sequencing depth. cluster of faecal samples (figure 1). This result suggested They obtained roughly 40 000 high-quality reads for the that the majority of GF microbiota might originate from sequence analysis from 45
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