Guardians within: Cross-talk between the gut microbiome and host immune system

Table 1 summarizes the key microbiota–immune interactions described in the manuscript

Microbiota	Metabolite/MAMP	Receptor/mechanism	Target cell	Effect/outcome
Segmented filamentous bacteria	Adhesion factors (MAMPs)	Microbial adhesion-triggered endocytosis uptake by IEC to SAA	IECs to Th17 cells	IEC-derived SAA drives IL-1β to Th17 differentiation
Citrobacter spp.	Bacterial antigens	Antigen presentation by IEC/DC: Uptake and peptide presentation by IECs or dendritic cells	Th17 cells	Pro-inflammatory Th17 responses
Clostridia clusters IV and XIVa	SCFAs (butyrate, propionate)	GPR43/GPR109A activation HDAC inhibition	Peripheral (p) Tregs	RORγt+ pTreg induction and expansion
Helicobacter spp./Helicobacter hepaticus	Microbial antigens	Antigen presentation by DC	RORγt+ pTregs	Promotes pTreg differentiation
Akkermansia muciniphila	MAMPs (outermembrane components)	Antigen presentation cytokine cues	RORγt+ pTregs	Supports pTreg induction
Faecalibacterium prausnitzii and Bacteroides fragilis	SCFAs (butyrate, acetate)	GPR41/GPR43 activation HDAC inhibition	Macrophages and dendritic cells	M2 polarization; enhanced IL-10; epigenetic priming for IL-6, tumor necrosis factor production
Bifidobacterium spp./Lactobacillus spp.	Recolonization antigens	GALT colonization	GALT progenitors	Restores GALT development and T cell maturation

For each microbial taxon, the principal metabolite or microbe-associated molecular pattern (MAMP), it produces is listed, along with the host sensing mechanism or receptor involved, the primary target cell type, and the resulting immunological effect or outcome. DC: Dendritic cell; GALT: Gut-associated lymphoid tissue; GPR: G protein-coupled receptor; HDAC: Histone deacetylase inhibition; IEC: Intestinal epithelial cell; IL: Interleukin; MAMP: Microbe-associated molecular pattern; pTreg: Peripheral regulatory T cell (RORγt+); SAA: Serum amyloid A; SCFAs: Short-chain fatty acids; Th: T helper; Tregs: Regulatory T.