Placebo-resistant gut bacteria: Akkermansia muciniphila spp. and Familial Mediterranean fever disease

Elya Pepoyan; Francesco Marotta; Anahit Manvelyan; Artak Galstyan; Lena Stepanyan; Hasmik Grigoryan; Liana Grigoryan; Mikayel Mikayelyan; Marine Balayan; Natalya Harutyunyan; Susanna Mirzabekyan; Vardan Tsaturyan; Tamas Torok; Astghik Pepoyan

doi:10.3389/fcimb.2024.1336752

Placebo-resistant gut bacteria: Akkermansia muciniphila spp. and Familial Mediterranean fever disease

Front Cell Infect Microbiol. 2024 Feb 23:14:1336752. doi: 10.3389/fcimb.2024.1336752. eCollection 2024.

Authors

Elya Pepoyan^{1

2

3}, Francesco Marotta⁴, Anahit Manvelyan^{1

2}, Artak Galstyan³, Lena Stepanyan^{1

2}, Hasmik Grigoryan^{1

2}, Liana Grigoryan¹, Mikayel Mikayelyan^{1

2}, Marine Balayan^{1

2}, Natalya Harutyunyan^{1

2}, Susanna Mirzabekyan^{1

2}, Vardan Tsaturyan^{2

3}, Tamas Torok⁵, Astghik Pepoyan^{1

2}

Affiliations

¹ Food Safety and Biotechnology Department, Scientific Research Institute of Food Science and Biotechnology, Armenian National Agrarian University, Yerevan, Armenia.
² International Association for Human and Animals Health Improvement, Yerevan, Armenia.
³ Faculty of Military Medicine, Yerevan State Medical University, Yerevan, Armenia.
⁴ ReGenera R&D International for Aging Intervention, Milan, Italy.
⁵ Lawrence Berkeley National Laboratory, Berkeley, CA, United States.

Abstract

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.

Keywords: Akkermansia muciniphila; Blautia; Enterobacteriaceae spp.; Faecalibacterium; familial Mediterranean fever; male patients; microbiome; placebo.

Publication types

Randomized Controlled Trial

MeSH terms

Adolescent
Adult
Akkermansia
Bacteria
Familial Mediterranean Fever* / drug therapy
Familial Mediterranean Fever* / microbiology
Gastrointestinal Microbiome*
Humans
Male
Middle Aged
Probiotics* / pharmacology
Young Adult

Supplementary concepts

Akkermansia muciniphila

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the State Committee of Science, Armenia (project 21AG-4D065).