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  • 1. Aims and Scope

    Gut and Liver is an international journal of gastroenterology, focusing on the gastrointestinal tract, liver, biliary tree, pancreas, motility, and neurogastroenterology. Gut atnd Liver delivers up-to-date, authoritative papers on both clinical and research-based topics in gastroenterology. The Journal publishes original articles, case reports, brief communications, letters to the editor and invited review articles in the field of gastroenterology. The Journal is operated by internationally renowned editorial boards and designed to provide a global opportunity to promote academic developments in the field of gastroenterology and hepatology. +MORE

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    Yong Chan Lee Professor of Medicine
    Director, Gastrointestinal Research Laboratory
    Veterans Affairs Medical Center, Univ. California San Francisco
    San Francisco, USA

    Deputy Editor

    Deputy Editor
    Jong Pil Im Seoul National University College of Medicine, Seoul, Korea
    Robert S. Bresalier University of Texas M. D. Anderson Cancer Center, Houston, USA
    Steven H. Itzkowitz Mount Sinai Medical Center, NY, USA
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Letter to the Editor

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Comments on Efficacy of a Synbiotic Containing Lactobacillus paracasei DKGF1 and Opuntia humifusa in Elderly Patients with Irritable Bowel Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial

Kwang Woo Kim

Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea

Correspondence to: Kwang Woo Kim
ORCID https://orcid.org/0000-0002-5379-1016
E-mail labottw5@snu.ac.kr

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Gut Liver 2023;17(6):954-955. https://doi.org/10.5009/gnl230446

Published online November 15, 2023, Published date November 15, 2023

Copyright © Gut and Liver.

To the Editor:

A recently published randomized controlled trial by Oh et al.1 elucidated the efficacy of specific synbiotics in older patients with irritable bowel syndrome (IBS), regardless of disease subtype, by assessing the rates of improvement in global IBS symptoms and abdominal symptom reduction. The synbiotic combination of Lactobacillus paracasei DKGF1 and prebiotics from Opuntia humifusa appears to provide relief from IBS symptoms, particularly abdominal pain, and psychological well-being in older patients. Subgroup analysis revealed that patients with constipation-dominant IBS or diarrhea-dominant IBS experienced improvements in altered bowel habits and abdominal pain. To the best of our knowledge, this is the first randomized controlled trial to evaluate the efficacy and safety of synbiotics in older patients with IBS.

The interest for clinical efficacy of gut microbiome has gained momentum since van Nood et al.2 reported the efficacy of fecal microbiota transplantation in patients with Clostridioides difficile infection. Since then, numerous studies have reported on the efficacy of microbiome in various diseases and phenotypes.3-6 IBS was no exception; it has been a significant concern in the realm of gastrointestinal disorder due to its high prevalence. It has been reported to affect approximately 11% of the global population, surpassing the numerical impact of most other diseases.7 Several studies have explored the relationship between the gut microbiome and IBS.8-10 The prevailing hypothesis suggests that dysbiosis may lead to alteration in the immune system within the gastrointestinal tract, resulting in low-grade inflammation and the onset of IBS. However, as reported in this study, various microbial treatments for IBS have shown controversial results. From this perspective, this study provides clinically important results.

While this study is interesting and significant in the context of the microbial treatment of IBS, I would like to address some concerns. First, although the authors mentioned a similar limitation in the Discussion section, because the treatment was related to the gut microbiome, it is advisable to conduct an analysis of the fecal microbiota, including measures of alpha- and beta-diversity, 16s RNA sequencing profile, and additional assessments of the metabolomic pathway, as well as related cytokine or messenger RNA expression levels. Microbial analysis may be performed at the initiation and conclusion of the study, enabling the comparison of differences between the two groups and intragroup changes before and after treatment. Given that this was a randomized controlled trial, these microbial-level differences could be adjusted to assess the efficacy of microbial treatment in comparison to a placebo.

Second, it would have been beneficial to gather baseline dietary data from the study population. Dietary intake is also associated with IBS symptoms. Although it shows heterogeneity according to individuals, regions, and ethnicities, it seems to play a role in modulating the gut microbiome.11,12 As the synbiotics in this study were a combination of ingredients from kimchi and cactus, the dietary intake of these items might have had a similar impact on the synbiotics. Furthermore, other dietary components could alleviate IBS symptoms, such as turmeric or prunes, which have been proven to help improve altered gastrointestinal symptoms.13,14 Although dietary control might be challenging in practice, it could introduce a bias in estimating the efficacy of microbial treatments.

In addition, there are some minor concerns. Although the role of the appendix has not yet been clearly elucidated, it is believed to play a role in modulating the gut microbiome. Therefore, a stratification analysis based on the history of appendectomy might be included. Additionally, the sample sizes for diarrhea-dominant IBS and constipation-dominant IBS were relatively small, and the number of patients in each treatment group was insufficient to obtain statistically significant results. More patients are required for a robust analysis. Finally, there seemed to be a typographical error in the phrase “Allocated to placebo (n=33)” in Figure 1, the last flowchart of the “allocation to synbiotics.”

In conclusion, as the authors noted, combining microbial analysis and dietary profiles with a large sample size would further strengthen the findings of this study. Despite these concerns, this study provided meaningful and essential evidence for microbial treatment in older patients with IBS.

No potential conflict of interest relevant to this article was reported.

  1. Oh JH, Jang YS, Kang D, et al. Efficacy of a synbiotic containing Lactobacillus paracasei DKGF1 and Opuntia humifusa in elderly patients with irritable bowel syndrome: a randomized, double-blind, placebo-controlled trial. Gut Liver 2023;17:100-107.
    Pubmed KoreaMed CrossRef
  2. van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med 2013;368:407-415.
    Pubmed CrossRef
  3. Kim SH, Lim YJ. The role of microbiome in colorectal carcinogenesis and its clinical potential as a target for cancer treatment. Intest Res 2022;20:31-42.
    Pubmed KoreaMed CrossRef
  4. Bamba S, Inatomi O, Nishida A, et al. Relationship between the gut microbiota and bile acid composition in the ileal mucosa of Crohn's disease. Intest Res 2022;20:370-380.
    Pubmed KoreaMed CrossRef
  5. Sehgal K, Khanna S. Gut microbiome and checkpoint inhibitor colitis. Intest Res 2021;19:360-364.
    Pubmed KoreaMed CrossRef
  6. Shin SY, Kim Y, Kim WS, et al. Compositional changes in fecal microbiota associated with clinical phenotypes and prognosis in Korean patients with inflammatory bowel disease. Intest Res 2023;21:148-160.
    Pubmed KoreaMed CrossRef
  7. Canavan C, West J, Card T. The epidemiology of irritable bowel syndrome. Clin Epidemiol 2014;6:71-80.
    Pubmed KoreaMed CrossRef
  8. Labus JS, Hollister EB, Jacobs J, et al. Differences in gut microbial composition correlate with regional brain volumes in irritable bowel syndrome. Microbiome 2017;5:49.
    Pubmed KoreaMed CrossRef
  9. Jeffery IB, O'Toole PW, Öhman L, et al. An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota. Gut 2012;61:997-1006.
    Pubmed CrossRef
  10. Tap J, Derrien M, Törnblom H, et al. Identification of an intestinal microbiota signature associated with severity of irritable bowel syndrome. Gastroenterology 2017;152:111-123.
    Pubmed CrossRef
  11. Jung KW, Myung SJ. An Asian perspective on irritable bowel syndrome. Intest Res 2023;21:189-195.
    Pubmed KoreaMed CrossRef
  12. Shafiee NH, Razalli NH, Mokhtar NM, Tan E, Ali RAR. An evaluation of dietary adequacy among patients with constipation-predominant irritable bowel syndrome in Malaysia. Intest Res 2022;20:124-133.
    Pubmed KoreaMed CrossRef
  13. Jafarzadeh E, Shoeibi S, Bahramvand Y, et al. Turmeric for treatment of irritable bowel syndrome: a systematic review of population-based evidence. Iran J Public Health 2022;51:1223-1231.
    Pubmed KoreaMed CrossRef
  14. Koyama T, Nagata N, Nishiura K, Miura N, Kawai T, Yamamoto H. Prune juice containing sorbitol, pectin, and polyphenol ameliorates subjective complaints and hard feces while normalizing stool in chronic constipation: a randomized placebo-controlled trial. Am J Gastroenterol 2022;117:1714-1717.
    Pubmed KoreaMed CrossRef

Article

Letter to the Editor

Gut and Liver 2023; 17(6): 954-955

Published online November 15, 2023 https://doi.org/10.5009/gnl230446

Copyright © Gut and Liver.

Comments on Efficacy of a Synbiotic Containing Lactobacillus paracasei DKGF1 and Opuntia humifusa in Elderly Patients with Irritable Bowel Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial

Kwang Woo Kim

Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea

Correspondence to:Kwang Woo Kim
ORCID https://orcid.org/0000-0002-5379-1016
E-mail labottw5@snu.ac.kr

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Body

To the Editor:

A recently published randomized controlled trial by Oh et al.1 elucidated the efficacy of specific synbiotics in older patients with irritable bowel syndrome (IBS), regardless of disease subtype, by assessing the rates of improvement in global IBS symptoms and abdominal symptom reduction. The synbiotic combination of Lactobacillus paracasei DKGF1 and prebiotics from Opuntia humifusa appears to provide relief from IBS symptoms, particularly abdominal pain, and psychological well-being in older patients. Subgroup analysis revealed that patients with constipation-dominant IBS or diarrhea-dominant IBS experienced improvements in altered bowel habits and abdominal pain. To the best of our knowledge, this is the first randomized controlled trial to evaluate the efficacy and safety of synbiotics in older patients with IBS.

The interest for clinical efficacy of gut microbiome has gained momentum since van Nood et al.2 reported the efficacy of fecal microbiota transplantation in patients with Clostridioides difficile infection. Since then, numerous studies have reported on the efficacy of microbiome in various diseases and phenotypes.3-6 IBS was no exception; it has been a significant concern in the realm of gastrointestinal disorder due to its high prevalence. It has been reported to affect approximately 11% of the global population, surpassing the numerical impact of most other diseases.7 Several studies have explored the relationship between the gut microbiome and IBS.8-10 The prevailing hypothesis suggests that dysbiosis may lead to alteration in the immune system within the gastrointestinal tract, resulting in low-grade inflammation and the onset of IBS. However, as reported in this study, various microbial treatments for IBS have shown controversial results. From this perspective, this study provides clinically important results.

While this study is interesting and significant in the context of the microbial treatment of IBS, I would like to address some concerns. First, although the authors mentioned a similar limitation in the Discussion section, because the treatment was related to the gut microbiome, it is advisable to conduct an analysis of the fecal microbiota, including measures of alpha- and beta-diversity, 16s RNA sequencing profile, and additional assessments of the metabolomic pathway, as well as related cytokine or messenger RNA expression levels. Microbial analysis may be performed at the initiation and conclusion of the study, enabling the comparison of differences between the two groups and intragroup changes before and after treatment. Given that this was a randomized controlled trial, these microbial-level differences could be adjusted to assess the efficacy of microbial treatment in comparison to a placebo.

Second, it would have been beneficial to gather baseline dietary data from the study population. Dietary intake is also associated with IBS symptoms. Although it shows heterogeneity according to individuals, regions, and ethnicities, it seems to play a role in modulating the gut microbiome.11,12 As the synbiotics in this study were a combination of ingredients from kimchi and cactus, the dietary intake of these items might have had a similar impact on the synbiotics. Furthermore, other dietary components could alleviate IBS symptoms, such as turmeric or prunes, which have been proven to help improve altered gastrointestinal symptoms.13,14 Although dietary control might be challenging in practice, it could introduce a bias in estimating the efficacy of microbial treatments.

In addition, there are some minor concerns. Although the role of the appendix has not yet been clearly elucidated, it is believed to play a role in modulating the gut microbiome. Therefore, a stratification analysis based on the history of appendectomy might be included. Additionally, the sample sizes for diarrhea-dominant IBS and constipation-dominant IBS were relatively small, and the number of patients in each treatment group was insufficient to obtain statistically significant results. More patients are required for a robust analysis. Finally, there seemed to be a typographical error in the phrase “Allocated to placebo (n=33)” in Figure 1, the last flowchart of the “allocation to synbiotics.”

In conclusion, as the authors noted, combining microbial analysis and dietary profiles with a large sample size would further strengthen the findings of this study. Despite these concerns, this study provided meaningful and essential evidence for microbial treatment in older patients with IBS.

CONFLICTS OF INTEREST

No potential conflict of interest relevant to this article was reported.

References

  1. Oh JH, Jang YS, Kang D, et al. Efficacy of a synbiotic containing Lactobacillus paracasei DKGF1 and Opuntia humifusa in elderly patients with irritable bowel syndrome: a randomized, double-blind, placebo-controlled trial. Gut Liver 2023;17:100-107.
    Pubmed KoreaMed CrossRef
  2. van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med 2013;368:407-415.
    Pubmed CrossRef
  3. Kim SH, Lim YJ. The role of microbiome in colorectal carcinogenesis and its clinical potential as a target for cancer treatment. Intest Res 2022;20:31-42.
    Pubmed KoreaMed CrossRef
  4. Bamba S, Inatomi O, Nishida A, et al. Relationship between the gut microbiota and bile acid composition in the ileal mucosa of Crohn's disease. Intest Res 2022;20:370-380.
    Pubmed KoreaMed CrossRef
  5. Sehgal K, Khanna S. Gut microbiome and checkpoint inhibitor colitis. Intest Res 2021;19:360-364.
    Pubmed KoreaMed CrossRef
  6. Shin SY, Kim Y, Kim WS, et al. Compositional changes in fecal microbiota associated with clinical phenotypes and prognosis in Korean patients with inflammatory bowel disease. Intest Res 2023;21:148-160.
    Pubmed KoreaMed CrossRef
  7. Canavan C, West J, Card T. The epidemiology of irritable bowel syndrome. Clin Epidemiol 2014;6:71-80.
    Pubmed KoreaMed CrossRef
  8. Labus JS, Hollister EB, Jacobs J, et al. Differences in gut microbial composition correlate with regional brain volumes in irritable bowel syndrome. Microbiome 2017;5:49.
    Pubmed KoreaMed CrossRef
  9. Jeffery IB, O'Toole PW, Öhman L, et al. An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota. Gut 2012;61:997-1006.
    Pubmed CrossRef
  10. Tap J, Derrien M, Törnblom H, et al. Identification of an intestinal microbiota signature associated with severity of irritable bowel syndrome. Gastroenterology 2017;152:111-123.
    Pubmed CrossRef
  11. Jung KW, Myung SJ. An Asian perspective on irritable bowel syndrome. Intest Res 2023;21:189-195.
    Pubmed KoreaMed CrossRef
  12. Shafiee NH, Razalli NH, Mokhtar NM, Tan E, Ali RAR. An evaluation of dietary adequacy among patients with constipation-predominant irritable bowel syndrome in Malaysia. Intest Res 2022;20:124-133.
    Pubmed KoreaMed CrossRef
  13. Jafarzadeh E, Shoeibi S, Bahramvand Y, et al. Turmeric for treatment of irritable bowel syndrome: a systematic review of population-based evidence. Iran J Public Health 2022;51:1223-1231.
    Pubmed KoreaMed CrossRef
  14. Koyama T, Nagata N, Nishiura K, Miura N, Kawai T, Yamamoto H. Prune juice containing sorbitol, pectin, and polyphenol ameliorates subjective complaints and hard feces while normalizing stool in chronic constipation: a randomized placebo-controlled trial. Am J Gastroenterol 2022;117:1714-1717.
    Pubmed KoreaMed CrossRef
Gut and Liver

Vol.17 No.6
November, 2023

pISSN 1976-2283
eISSN 2005-1212

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