Table 1.

Signal classes, routes, recognition, and evidence boundaries.

Signal class	Candidate source(s)	Possible route	Recognition/relay	Evidence state and interpretive boundary
Host-derived DAMPs	Injured brain and other damaged host tissues	Local release; cerebrospinal fluid; blood	TLR2/4, RAGE, cGAS-STING, NLRP3	Sterile inflammatory pathways are established in experimental stroke (1–10). Shared receptor activation must not be interpreted as microbial exposure.
Viable bacteria	Gut, oral cavity, airway, or another colonized/infected site	Barrier crossing to lymph/blood; aspiration; local-to-systemic dissemination	Organism-dependent pattern-recognition receptors (PRRs) and host-cell responses	Selected models report culture-positive bacterial recovery in peripheral compartments and source-linked gut-to-periphery dissemination (18–22). Functional leak and translocation were not consistent across all models (23); gut Enterobacteriaceae expansion was not required for lung colonization in another model (95). Interpret each result within its model and use viability and source controls for live-bacteria claims.
Structural microbial products	Microbial communities or infection; anatomical source often unresolved	Barrier crossing; blood/lymph; local tissue exposure	LPS: LBP-CD14-MD-2/TLR4; other products: TLR2, NOD1/2, endosomal/cytosolic sensors	Peh et al. detected peptidoglycan/LPS-positive structures and bacterial 16S signal in blood and ischemic brain; the germ-free comparison supports microbiota dependence, but strain-level gut-to-brain origin and viability in brain remain unresolved (24). Molecular detection or receptor recognition does not by itself demonstrate intestinal crossing (11, 24, 57, 59, 96).
Microbial metabolites	Microbiota plus diet and host metabolism	Physiological absorption; portal metabolism; systemic circulation	G-protein-coupled receptors (GPCRs), histone deacetylases, metabolic and immune pathways	Context-dependent associations and experimental effects (54, 60–65, 80–86, 89, 90, 92, 97, 101–104). Do not label metabolites as bacterial translocation; account for diet, medication, kidney and liver function.
Community composition	Stool, oral, or airway microbiota	Composition alone does not measure transport	Not applicable	Human association and prediction studies (28–44, 47–53, 55, 56). Taxonomic abundance does not prove source, passage, or causality.

Distinct signal classes require different route models and evidentiary standards. DAMPs, viable microorganisms, structural microbial products, metabolites, and microbial community composition should not be grouped under a single concept of “translocation.” Source attribution and causal role are evaluated separately. NOD1/2 denotes nucleotide-binding oligomerization domain-containing proteins 1 and 2.