Table 1.

Major preclinical studies of traumatic brain injury and its effects on the fecal microbiome and/or intestinal barrier. Arrows indicate a significant change (increase or decrease) and ↔ indicates no significant change compared to uninjured controls; we only selected microbial composition changes shown. TBI—traumatic brain injury; HS—hemorrhagic shock. TBI^†—open; TBI^§—closed head injury; NS—not studied.

	Author and Year	Species	Trauma Model	Time Point(s) Studied Postinjury	Fecal Microbiome Diversity and Composition Changes	Intestinal Barrier Effects
Age matters: microbiome depletion prior to repeat mild traumatic brain injury differentially alters microbial composition and function in adolescent and adult rats	Sgro et al., 2022 [33]	Male and Female Sprague-Dawley Rats	TBI§ (repetitive)	17 and 30 days	↔ Alpha-diversity (30 d) ↔ Beta-diversity (30 d) ↔ Microbial composition (30 d)	↔ Tight-junction protein expression in small intestine (30 d) ↓ Occludin expression in small intestine (30 d)
Traumatic brain injury induces gastrointestinal dysfunction and dysbiosis of gut microbiota accompanied by alterations in bile acid profile	You et al., 2022 [19]	Male C57BL/6J Mice	TBI†	1 h, 6 h, 1, 3, and 7 days	↓ Alpha-diversity (all time points) Beta-diversity differences (1 d, 3 d, 7 d) ↓ Firmicutes (6 h) ↑ Bacteroidetes, Proteobacteria (6 h) Changes in genus composition over time	↔ ZO-1 expression in colon and small intestine (1 d, 3 d) ↓ Occludin expression in colon (3 d) ↓ Claudin-1 expression in small intestine (1 d, 3 d), colon (1 d) ↓ Claudin-2 expression in small intestine (3 d), colon (1 d)
Translocation and dissemination of gut bacteria after severe traumatic brain injury	Yang et al., 2022 [20]	Male C57BL/6 Mice	TBI†	3 h, 1, 3, 7, and 14 days	↑ Alpha-diversity (3 d, 7 d) Beta-diversity differences ↓ Firmicutes, Lactobacillus, Akkermansia, Roseburia (7 d) ↑ Bacteroidetes, Streptococcus, Lachnoclostridium (7 d)	↑ Villous atrophy in small intestine (1 d, 3 d, 7 d, 14 d) ↓ Lysozyme from Paneth cells in small intestine (3 d) ↑ Caspase-3 in small intestine (1 d, 3 d, 7 d, 14 d)
Oral administration of brain protein combined with probiotics induces immune tolerance through the tryptophan pathway	Hou et al., 2021 [21]	Male Sprague-Dawley Rats	TBI†	3 and 7 days	↓ Alpha-diversity (3 d) Beta-diversity differences ↑ Akkermansia (3 d) ↓ Lactobacillus (3 d, 7 d), Parabacteroides (7 d)	↓ Claudin in colon, small intestine (3 d, 7 d) ↓ Occludin in colon, small intestine (3 d, 7 d) ↑ Plasma fluorescein isothiocyanate-dextran (3 d, 7 d)
Sustained dysbiosis and decreased fecal short-chain fatty acids after traumatic brain injury and impact on neurologic outcome	Opevemi et al., 2021 [41]	Male C57BL6/J Mice	TBI†	3 h, 1, 3, 7, 14, and 28 days	↓ Alpha-diversity (7 d, 14 d, 28 d) Beta-diversity differences ↑ Verrucomicrobiaceae, Erysipelotrichaceae ↓ Lachnospiraceae, Ruminococcaceae, Bacteroidaceae	NS
Effects of traumatic brain injury on the gut microbiota composition and serum amino acid profile in rats	Taraskina et al., 2022 [24]	Male Wistar Rats	TBI†	7 days	↓ Alpha-diversity Beta-diversity differences ↓ Bacteroidetes ↑ Rikenellaceae, Prevotellaceae, Lactobacillus, Turicibacter, Helicobacter	NS
Traumatic brain injury in mice induces acute bacterial dysbiosis within the fecal microbiome	Treangen et al., 2018 [18]	Male C57BL/6J Mice	TBI†	24 h	↓ Lactobacillus ↑ Marvinbryantia, Clostridiales	NS
Moderate traumatic brain injury alters the gastrointestinal microbiome in a time-dependent manner	Nicholson et al., 2019 [23]	Male Sprague-Dawley Rats	TBI†	2 h, 1, 3, and 7 days	↓ Alpha-diversity (3 d) Beta-diversity differences (1 d, 3 d) ↓ Firmicutes (1 d, 3 d), Lachnospiraceae (2 h, 3 d), Mogibacteriaceaei (1 d, 3 d) ↑ Bacteroidaceae (1 d), Verrucomicrobia (1 d), Enterobacteriaceae (3 d)	NS
Differential fecal microbiome dysbiosis after equivalent traumatic brain injury in aged versus young adult mice	Davis 4th et al., 2021 [32]	Male C57BL/6 Mice	TBI†	1, 7, and 28 days	↔ Beta-diversity over time ↑ Clostridium clocleatum, Anaerostipes, Lactobacillus, Coprococcus	NS
Susceptibility to epilepsy after traumatic brain injury is associated with preexistent gut microbiome profile	Medel-Matus et al., 2022 [26]	Male and Female Sprague-Dawley Rats	TBI†	7 days, 1 month, and 7 months	↔ Alpha-diversity over time Beta-diversity differences over time ↓ Lachnospiraceae (7 d, 1 mo, 7 mo), Lactobaccillus (1 mo) ↑ Ruminiclostridium, Pseudomonas (7 d), Bacteroides (1 mo), Parabacteroides (7 mo)	NS
Traumatic brain injury alters the gut-derived serotonergic system and associated peripheral organs	Mercado et al., 2022 [38]	Male C57BL/6J Mice	TBI†	1, 3, and 7 days	↓ Clostridium leptum (7 d) ↑ Clostridium scindens (7 d)	NS
Acute gut microbiome changes after traumatic brain injury are associated with chronic deficits in decision making and impulsivity in male rats	Frankot et al., 2023 [25]	Male Long-Evans Rats	TBI†	3, 30, and 60 days	↓ Alpha-diversity (3 d v 30 d) Beta-diversity differences over time ↓ Firmicutes, Bacteroides	NS
An integrated analysis of gut microbiota and the brain transcriptome reveals host–gut microbiota interactions following traumatic brain injury	Bao et al., 2023 [22]	Male C57BL/6 Mice	TBI†	7 days	↔ Alpha-diversity ↔ Beta-diversity ↑ Actinobacteria, Bifidobacteriales, Bifidobacteriaceae, Bifidobacterium	NS
Bidirectional brain–gut interactions and chronic pathological changes after traumatic brain injury in mice	Ma et al., 2017 [34]	Male C57BL/6 Mice	TBI†	24 h, 28 days	NS	↑ Colonic injury (28 d) ↔ Jejunal injury (24 h, 28 d) ↓ Transepithelial electrical resistance in jejunum (24 h) ↑ Paracellular flux in colon (28 d) ↔ ZO-1 in colon (28 d) ↔ Occludin expression in colon (28 d) ↓ Claudin-1 in colon (28 d) ↔ Claudin-2 in colon (28 d)
CORM-3 exerts a neuroprotective effect in a rodent model of traumatic brain injury via the bidirectional gut–brain interactions	Zhang et al., 2021 [35]	Male Sprague-Dawley Rats	TBI† & HS	24 h, 30 days	NS	Jejunal histological changes at 24 h postinjury characterized by cleaved caspase-1-positive cells, pyroptotic cells
Disruption of the intestinal barrier and endotoxemia after traumatic brain injury: implications for post-traumatic epilepsy	Mazarati et al., 2021 [36]	Male Sprague-Dawley Rats	TBI†	1 week, 7 months	NS	↑ Plasma lipopolysaccharide (1 week, 7 month) ↑ Plasma fluorescein isothiocyanate-labeled dextran (1 week, 7 month)