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

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.

Figure 1

Hybridization scores of altered gut bacterial diversities in non-FMF and FMF men after the placebo administration. The impact of the placebo on 18,725 bacterial OTUs was evaluated; P < 0.0001. FMF – Familial Mediterranean fever. OTUs – operational taxonomic units. (A) Hybridization score of Ruminococcus OTUs after placebo in non-FMF men. (B) Hybridization score of Ruminococcus OTUs after placebo in FMF men. (C) Hybridization score of Lachnospiraceae OTUs after placebo in non-FMF men. (D) Hybridization score of Lachnospiraceae OTUs after placebo in FMF men. (E) Hybridization score of Bacteroidia OTUs after placebo in non-FMF men. (F) Hybridization score of Bacteroidia OTUs after placebo in FMF men. (G) Hybridization score of Escherichia OTUs after placebo in FMF men.

Figure 2

Overlapping gut bacterial diversities of family Lachnospiraceae in non-FMF and FMF men after the placebo administration (number of OTUs). P < 0001. FMF, Familial Mediterranean fever; OTUs, operational taxonomic units; g, genus.

Figure 3

Overlapping gut bacterial diversities of family Ruminococcaceae in non-FMF and FMF men after the placebo administration (number of OTUs). P < 0001. FMF, Familial Mediterranean fever; OTUs, operational taxonomic units; g, genus; f, family.