Comparative Genomic Insights into Pangenome Diversity and Functional Adaptation of Akkermansia and Faecalibacterium as Gut-Associated Next-Generation Probiotics: A Systematic Review

Abstract

Background Gut-associated next-generation probiotics (NGPs), particularly Akkermansia and Faecalibacterium , are promising candidates for restoring gut homeostasis and managing dysbiosis-related diseases. Comparative genomics can reveal their pangenome diversity, lineage-specific traits, and functional adaptations. This review aimed to synthesize comparative genomic evidence on their probiotic-associated genomic features and identify current research gaps. Methods A systematic review was conducted in accordance with the PRISMA 2020 guidelines. Comprehensive literature searches were performed in PubMed, Scopus, and The Lens to identify original comparative genomic studies published between January 2020 and December 2025. From 167 records initially identified, 17 studies met the predefined eligibility criteria and were included in the qualitative synthesis. Data were systematically extracted and narratively synthesized to compare comparative genomic approaches, pangenome characteristics, and functional adaptations of Akkermansia and Faecalibacterium. Results Comparative genomics showed that Akkermansia and Faecalibacterium have high genomic diversity, open pangenomes, and large accessory or strain-specific gene repertoires, indicating lineage- and strain-dependent probiotic potential. Akkermansia was mainly characterised by functional traits associated with the utilization of mucin, human milk oligosaccharides, and host-glycan. These traits were accompanied by mucin-degrading enzymes, epithelial adherence-related features, pili, autotransporters, oxygen-tolerance mechanisms, and genes associated with vitamin B12 biosynthesis. In contrast, Faecalibacterium showed broader carbohydrate utilization, glycan-degrading enzymes, trehalose metabolism, extracellular polysaccharide (EPS) or capsule genes, acetate/butyrate-associated metabolism, and strain-specific anti-inflammatory traits. Conclusions Comparative genomics provides a useful framework for strain-level prioritization of Akkermansia and Faecalibacterium as gut-associated next-generation probiotic candidates. The evidence indicated broad pangenome diversity and lineage-dependent functional potential in both genera. However, safety-related genomic features, including antimicrobial resistance genes, virulence or pathogenicity markers, horizontal gene transfer signals, and risk indices, were assessed unevenly across studies. Future development of these taxa as next-generation probiotics should therefore combine comparative genomics with standardized genome-based safety screening and experimental functional validation. Systematic Review Registration This systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO; Registration No. CRD420261437920) on July 2, 2026.