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Updated: Jul 1, 2025

Microbiota Analysis Using Two-step PCR and Next-generation 16S rRNA Gene Sequencing
Published on: October 15, 2019
Placebo-resistant gut bacteria: Akkermansia muciniphila spp. and Familial Mediterranean fever disease
Elya Pepoyan1,2,3, Francesco Marotta4, Anahit Manvelyan1,2
1Food Safety and Biotechnology Department, Scientific Research Institute of Food Science and Biotechnology, Armenian National Agrarian University, Yerevan, Armenia.
Introduction:
Despite numerous investigations into the impact of drugs/probiotics on the gut microbiota composition in Familial Mediterranean Fever (FMF) patients, the question as to whether there exists a significant bacterial diversity(ies) independent of the placebo effect that can be reliably considered in clinical and nutritional trials remains unresolved.
Methods:
This study represents the in augural analysis of the placebo's influence on the gut microbiota of both healthy individuals and FMF afflicted men, utilizing previously collected data from PhyloChip™ DNA microarray experiments. A total of 15 healthy and 15 FMF male volunteers, aged 18 to 50, participated in this partially randomized placebo trial, which is accessible through the GEO Series accession number GSE111835.
Results And Discussion:
Key findings from current investigations include i. the anticipated divergence in gut bacteria resistance to placebo between healthy and FMF individuals, ii. the minor impact of placebo on gut bacterial diversities in healthy individuals, with Enterobacteriaceae diversities identified as placebo-resistant among "healthy" gut bacteria, and iii. the comprehensive influence of placebo on all bacterial phyla in the gut microbiome of FMF patients, extending to nearly all bacterial genera, except for the resilience of gut Akkermansia muciniphila spp. to placebo in FMF patients. This study underscores the susceptibility of Faecalibacterium, Blautia, and Clostridium genera to placebo. Consequently, this investigation holds significance for the proper design of placebo-controlled trials and establishes a foundation for further exploration of the gut-brain axis. Furthermore, it contributes valuable insights to discussions regarding proposals for probiotic therapies, particularly focusing on Faecalibacterium spp., Blautia spp., and Clostridium spp.
Insights
Familial Mediterranean Fever (FMF) patients’ gut bacteria are significantly impacted by placebo, unlike healthy individuals. Certain gut bacteria, like Akkermansia muciniphila, show placebo resistance in FMF patients, informing clinical trial design.
Area of Science:
- Microbiology
- Gastroenterology
- Clinical Trials
Background:
- Gut microbiota composition is crucial in Familial Mediterranean Fever (FMF) pathogenesis and treatment.
- The influence of placebo on gut microbiota in FMF patients remains unclear, complicating clinical trial interpretations.
Purpose of the Study:
- To investigate the placebo effect on gut microbiota composition in healthy individuals versus FMF patients.
- To identify bacterial taxa resistant or susceptible to placebo in both groups.
Main Methods:
- Analysis of previously collected PhyloChip™ DNA microarray data.
- Inclusion of 15 healthy and 15 FMF male volunteers (aged 18-50).
- Partially randomized placebo-controlled trial design (GEO Series accession number GSE111835).
Main Results:
- Healthy individuals showed minor placebo impact on gut bacteria, with Enterobacteriaceae being placebo-resistant.
- FMF patients exhibited comprehensive placebo influence across most gut bacterial phyla and genera.
- Akkermansia muciniphila in FMF patients and Enterobacteriaceae in healthy individuals demonstrated placebo resistance.
Conclusions:
- Placebo significantly affects gut microbiota in FMF patients, necessitating careful trial design.
- Findings provide insights into placebo-resistant bacteria, guiding future probiotic therapy development for FMF.
- Understanding placebo effects is critical for interpreting gut microbiota studies and designing effective interventions.
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