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Efficacy of Prebiotics and Probiotics for Functional Dyspepsia

Prebiotics and probiotics have been widely used in functional dyspepsia treatment. It is because the functional dyspepsia pathophysiology is thought to be related to various factors, including: 
  • the imbalance of intestinal flora, 
  • changes in gastrointestinal motility, 
  • visceral hypersensitivity, 
  • dysregulation of the gut-brain axis, 
  • and psychological disorders, 
  • mild inflammation, 
  • and immune dysfunction. 
Until now, no definitive management for functional dyspepsia. The use of prebiotics and probiotics for this purpose is still controversial.

Efficacy of Prebiotics and Probiotics for Functional Dyspepsia
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Overview of Prebiotics and Probiotics

According to the International Scientific Association of Probiotics and Prebiotics (ISAPP), dietary prebiotics are the selective ingredients that will undergo fermentation to produce changes in the composition and or activity of gastrointestinal microbiota that benefit the health of the host.

Prebiotics are resistant to gastric acid, are not hydrolyzed by the host digestive enzymes, and are not absorbed by the digestive tract, but are fermented by intestinal microbiota. 

The prebiotic type consists of:
  1. fructans such as inulin and fructooligosaccharides such as oligofructose, galactooligosaccharides, 
  2. starches and glucose-derived oligosaccharides such as polydextrose,
  3. pectic oligosaccharide such as pectin, and non-carbohydrate oligosaccharides, 
  4. starches and glucose-derived oligosaccharides such as polydextrose,
  5. pectic oligosaccharide such as pectin, and non-carbohydrate oligosaccharides such as starch and glucose-derived oligosaccharides such as polydextrose, 
  6. pectic oligosaccharide such as pectin, and non-carbohydrate oligosaccharides such as starch and glucose-derived oligosaccharides such as polydextrose, 
  7. pectic oligosaccharide such as pectin, and non-carbohydrate oligosaccharides like starch and cocoa-derived oligosaccharides.


According to the Food and Agriculture Organization of the United Nations and the World Health Organization (FAO / WHO), Probiotics are living microorganisms that provide health benefits to the host if given in sufficient quantities.

Probiotic microorganisms basically contain lactic acid-producing bacteria such as Bifidobacterium sp (adolescentis, animalis, bifidum, breve, and longum) and Lactobacillus sp (acidophilus, casei, fermentum, gasseri, johnsonii, paracasei, plantarum, breve, and longum) and Lactobacillus sp (acidophilus, casei, fermentum, gasseri, johnsonii, paracasei, plantarum, breve, and longum).

The use of probiotics and prebiotics in functional dyspepsia is assumed to be beneficial (as in irritable bowel syndrome), which is able to reduce mild inflammation and increase mucosal permeability by reducing or changing the intestinal microbiota or abnormal intestinal flora compositions.

Latest Scientific Evidence Related to the Efficacy of Prebiotics and Probiotics for Functional Dyspepsia

In 2019, Zhang et al. conducted a systematic review and meta-analysis that examined the efficacy of prebiotics and probiotics' affections for functional dyspepsia. They conducted medical literature searches on the MEDLINE database (from 1946 to 30 September 2018), EMBASE, EMBASE Classic (1947 to 30 September 2018), and the Cochrane central register of controlled trials.

Inclusion criteria only include:
  • The placebo-controlled randomized study in adult patients (over 16 years) who examined the effects of prebiotics, probiotics, or their combined products (synbiotic), with a duration of therapy of at least 7 days,
  • diagnosis of functional dyspepsia is established through diagnostic criteria,
  • negative findings of organic disorders in upper gastrointestinal endoscopy.

The primary outcomes examined included the effects of prebiotics and probiotics, or their combination (synbiotic) compared with placebo on symptoms of functional dyspepsia—the secondary output checks for adverse events caused by the above interventions.

Dichotomous data sets were analyzed as relative risk (RR) with a confidence level of 95% (95% CI), while continuous data were analyzed with a standardized or weighted mean difference. I2 test is used to evaluate heterogeneity between studies. Meta-analysis uses random-effect or fixed-effect models that are adjusted to the results of heterogeneity between studies. Publication bias is checked by the Egger test.

Zhang et al. identified 1062 citations consisting of 27 relevant articles, but only five studies that met the inclusion criteria consisted of 4 probiotic studies and 1 prebiotic study. There were no studies that examine combination products (synbiotic).

The 5 randomized controlled studies included 409 patients (210 received active therapy, and 199 received placebo). The probiotics used are Lactobacillus, Bifidobacterium, Streptococcus, Bacillus subtilis, and Bacilllus lichenformis. While the prebiotics used was Caraway Oil / L-Menthol.

The results of meta-analysis obtained RR 1.15 (95% CI 1.01-1.30) for improvement of symptoms of functional dyspepsia with the use of probiotics or prebiotics when compared with placebo. In other words, probiotics and prebiotic products did not provide a statistically significant benefit in the improvement of symptoms of functional dyspepsia, even though the results of studies included in the analysis show a trend of symptom improvement.

The five studies analyzed were evenly distributed when collected for the combined effect assessment, indicating that the publication bias of each study was quite minimal. There were no differences in adverse events between the intervention and placebo groups. Zhang et al. did not conduct sub-analyses to compare the efficacy of certain types of probiotic products due to the lack of data.


References
1. Zhang J, Wu HM, Wang X, Xie J, Li X, Ma J, Wang F, Tang X. Efficacy of prebiotics and probiotics for functional dyspepsia: A systematic review and meta-analysis. Medicine 2020;99:7(e19107).
2. Tziatzios G, Giamarellosbourboulis EJ, Papanikolaou IS, et al. Is small intestinal bacterial overgrowth involved in the pathogenesis of functional dyspepsia? Med Hypotheses 2017;106:26–32
3. Shimura S, Ishimura N, Mikami H, et al. Small intestinal bacterial overgrowth in patients with refractory functional gastrointestinal disorders. J Neurogastroenterol Motil 2016;22:60–8.
4. Hadizadeh F, Bonfiglio F, Belheouane M, et al. Faecal microbiota composition associates with abdominal pain in the general population. Gut 2017; Epub 2017 Aug 1. PubMed PMID: 28765473.
5. Vanheel H, Farré R. Changes in gastrointestinal tract function and structure in functional dyspepsia. Nat Rev Gastroenterol Hepatol 2013;10:142–9.
6. Davani-Davari D, Negahdaripour M, Karimzadeh I, Seifan M, Mohkam M, Masoumi SJ, Berenjian A, Ghasemi Y. Prebiotics: Definition, Types, Sources, Mechanisms, and Clinical Applications. Foods. 2019;8(3):92. DOI: 10.3390/foods8030092.
7. Hill, C. et al. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol 11, 506–514 (2014); published online 10 June 2014; DOI:10.1038/nrgastro.2014.66
8. Patel RM, Myers LS, Kurundkar AR, et al. Probiotic bacteria induce maturation of intestinal claudin 3 expression and barrier function. Am J Pathol 2012;180:626–35.
9. Igarashi M, Nakae H, Matsuoka T, et al. Alteration in the gastric microbiota and its restoration by probiotics in patients with functional dyspepsia. BMJ Open Gastroenterology 2017;4 :e000144.doi: 10.1136/bmjgast-2017-000144
10. Sarowska J et al. The therapeutic effect of probiotic bacteria on gastrointestinal disease. Adv Clin Exp Med.2013;22(5):759-66.
11. Chey WD, Lacy BE, Cash BD, Epstein M, Shah SM. Randomized Controlled Trial to Assess the Efficacy & Safety of Caraway Oil/L-Menthol Plus Usual Care Polypharmacy vs. Placebo Plus Usual Care Polypharmacy for Functional Dyspepsia. Gastroenterology, 152(5), S306. DOI:10.1016/s0016-5085(17)31313-6

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