Exploring exercise modalities and their impact on inflammatory bowel disease: A systematic review of rodent colitis models

Table 1 Characteristics of included studies

Ref.	Year	Experimental subjects	Modeling method	Exercise type	Exercise parameters
Kasimay et al[15]	2006	Sprague–Dawley rats	4% acetic acid, 1 mL, intracolonic administration	FTR	7 m/minute, 30 minutes/day, 3 days/week, total 6 weeks
Saxena et al[16]	2012	Adiponectin KO and WT C57BL/6 mice	2% DSS, drinking water, 5 days	FTR	18 m/minute, 55 minutes/day, 5 days/week, total 4 weeks
Cook et al[17]	2013	C57Bl/6 mice	2% DSS, drinking water, 5 days	FTR	8-12 m/minute, 40 minutes/day, 5 days/week, total 6 weeks, inclination of 5°
Bilski et al[18]	2015	Wistar rats	TNBS, 10 mg/kg in 50% ethanol, 250 μL, intracolonic administration	FTR	20 m/minute, 30 minutes/day, 5 days/week, total 6 weeks
Bilski et al[19]	2019	C57BL/6 mice	TNBS, 100 μg/g in 40% ethanol, 175 μL, intracolonic administration	FTR	7.2 m/minute, 30 minutes/day, 7 days/week, total 6 weeks
Qonitatillah et al[20]	2020	BALB/c mice	λ-carrageenan, 20 mg/L, drinking water, 6 weeks	FTR	7 m/minute, 30 minutes/day, 3 days/week, total 6 weeks
Van Mechelen et al[21]	2022	C57BL/6 mice	Acute colitis: 2% DSS, drinking water, 7 days; chronic colitis: Three cycles of 7 days DSS and 14 days recovery	FTR	11 m/minute, 60 minutes/day, 7 days/week, total 3 weeks, inclination of 5°
Hao et al[22]	2024	C57BL/6J mice	2% DSS, drinking water, 7 days	FTR	10 m/minute, 5 minutes × 10 bouts with 2 minutes of rest, 5 days/week, total 12 weeks
Jin et al[23]	2024	C57BL/6 mice	2% DSS, drinking water, 7 days	FTR	5 m/minute × 10 minutes, 8 m/minute × 50 minutes, total 14 days
Wojcik-Grzybek et al[24]	2024	C57BL/6 mice	TNBS, 4 mg in 50% ethanol, 175 μL, intracolonic administration	FTR	6 m/minute, 10 minutes/day, 5 days/week, total 6 weeks
Cook et al[17]	2013	C57BL/6 mice	2% DSS, drinking water, 5 days	VWR	30 days
Szalai et al[25]	2014	Wistar rats	TNBS, 10 mg in 0.25 mL of 50% ethanol, intracolonic administration	VWR	6 weeks
Liu et al[26]	2015	C57BL/6 mice	2% DSS, drinking water, 5 days	VWR	30 days
Mazur-Bialy et al[27]	2017	C57BL/6 mice	TNBS, 100 μg/g in 40% ethanol, 250 μL, intracolonic administration	VWR	6 weeks
Maillard et al[28]	2019	CEABAC10 transgenic mice	Bacterial exposure	VWR	12 weeks
Estaki et al[29]	2020	Muc2-/- and WT C57BL/6 mice	Muc2-/- idiopathic colitis	VWR	6 weeks
Wojcik-Grzybek et al[30]	2022	C57BL/6 mice	TNBS, 4 mg in 50% ethanol, 175 μL, intracolonic administration	VWR	7 weeks
Kolahi et al[31]	2023	C57BL/6 mice	1.5% DSS, drinking water, 7 days	Swimming	15-20 minutes/day, 5 days/week, for 6 weeks
Özbeyli et al[32]	2016	Sprague-Dawley rats	4% acetic acid, 1 mL, intracolonic administration	Swimming	30 minutes/day, 3 days/week, 5 weeks
de Oliveira Santos et al[33]	2021	Wistar rats	4% acetic acid, 1 mL, intracolonic administration	Swimming	1 hour/day, 5 days/week, 8 weeks
Özbeyli et al[32]	2016	Sprague-Dawley rats	4% acetic acid, 1 mL, intracolonic administration	Climb	Rats climbed vertical ladder with a load, 8 repeats 3 sets, 3 days/week, total 5 weeks
de Oliveira Santos et al[33]	2021	Wistar rats	4% acetic acid, 1 mL, intracolonic administration	Jump	Rats jump in the water with a load, 4 × 10 repetitions, 60 minutes/day, 5 days/week, total 8 weeks with progressive overload

KO: Knockout; WT: Wild-type; DSS: Dextran sulfate sodium; TNBS: Trinitro-benzene-sulfonic acid; FTR: Forced treadmill running; VWR: Voluntary wheel running.

Table 2 Impact of exercise on the outcomes of colitis animals fed normal diet

Ref.	Exercise type	Macroscopic parameters					Microscopic parameters				Conclusion
		Body weight change	Diarrhea and bloody stools	Disease activity index	Colon length or weight	Colon macroscopic injury	Histopathology scores	Blood inflammatory indicators	Colon inflammatory indicators	Colon oxidation/antioxidant balance
Szalai et al[25]	VWR	No statistical difference				Decreasing		TNF-α mRNA (no change); IL-1β mRNA (decreasing); CXCL1 mRNA (decreasing); IL-10 mRNA (decreasing)	MPO (decreasing); TNF-α mRNA (no change); IL-1β mRNA (decreasing); CXCL1 mRNA (decreasing); IL-10 mRNA (increasing); TNF-α protein (no change)	HO-1 (no change); cNOS (increasing); iNOS (decreasing)	Improving
Liu et al[26]	VWR	Increasing	Decreasing		No statistical difference		Decreasing		IL-1β mRNA (no change); IL-1β protein (no change); TNF-α mRNA (decreasing); TNF-α protein (decreasing); IL-6 mRNA (decreasing); IL-6 protein (decreasing)		Improving
Mazur-Bialy et al[27]	VWR	No statistical difference	Decreasing	No statistical difference	Increasing		Decreasing				Improving
Cook et al[17]	VWR	No statistical difference	Decreasing				No statistical difference	IL-6 mRNA (decreasing); TNF-α mRNA (decreasing); CXCL1 mRNA (decreasing)			Improving
Cook et al[17]	FTR	No statistical difference	Increasing				Increasing	IL-1β mRNA (increasing); IL-6 mRNA (increasing); IL-17 mRNA (increasing); IL-10 mRNA (increasing); CCL6 mRNA (increasing)			Exacerbating
Kasimay et al[15]	FTR					Decreasing	Decreasing		MPO (decreasing)	MDA (decreasing); GSH (decreasing)	Improving
Bilski et al[18]	FTR					Decreasing; CBF (increasing)		IL-1 protein (decreasing); TNF-α protein (decreasing); TWEAK (decreasing); IL-6 protein (increasing); irisin (increasing); leptin (decreasing); adiponectin (no change)	MPO (decreasing)		Improving
Bilski et al[19]	FTR			Increasing		Increasing	Increasing		IL-1 mRNA (increasing); IL-6 mRNA (increasing); TNF-α mRNA (increasing)	MDA (increasing); SOD1 mRNA (increasing); SOD2 mRNA (increasing); GPx mRNA (increasing); COX2 mRNA (increasing); iNOS mRNA (increasing); HIF-α protein (increasing)	Exacerbating
Hao et al[22]	FTR	Increasing		Decreasing	Increasing		Decreasing				Improving
Jin et al[23]	FTR	Increasing		Decreasing	Increasing		Decreasing	TNF-α (decreasing); IL-1β (decreasing); IL-6 (decreasing)			Improving
Van Mechelen et al[21]	FTR			No statistical difference			No statistical difference		CXCL1 (no change); CCL20 (no change); CCL2 (no change)		No impact
Saxena et al[16]	FTR	No statistical difference		No statistical difference	No statistical difference		No statistical difference; BrdU (no change)	Serum APN (increasing)	IL-6 (no change); IL-1β (no change); TNF-α (no change); IL-10 (no change)		No impact
Qonitatillah et al[20]	FTR						Increasing				Exacerbating
Kolahi et al[31]	Swimming	No statistical difference		Decreasing	Increasing		Decreasing		Collagen deposition (decreasing)	MDA (decreasing); DTNB (increasing); SOD (increasing); CAT (increasing)	Improving
de Oliveira Santos et al[33]	Swimming	Increasing			No statistical difference	Decreasing	Decreasing		MPO (decreasing); IL-1β (decreasing); IL-6 (decreasing); TNF-α (decreasing)	NO (decreasing); MDA (decreasing); SOD (increasing)	Improving
de Oliveira Santos et al[33]	Jumping	No statistical difference			Increasing	Decreasing	Decreasing		MPO (decreasing); IL-1β (decreasing); IL-6 (decreasing); TNF-α (decreasing)	NO (no change); MDA (decreasing); SOD (increasing)	Improving

All data were colitis + exercise vs colitis + sedentary. FTR: Forced treadmill running; VWR: Voluntary wheel running; CBF: Cerebral blood flow; BrdU: 5-bromo-2’-deoxyuridine; TNF: Tumor necrosis factor; mRNA: Messenger RNA; IL: Interleukin; TWEAK: Tumor necrosis factor-like weak inducer of apoptosis; APN: Adiponectin; MPO: Myeloperoxidase; HO-1: Heme oxygenase-1; iNOS: Inducible nitric oxide synthase; NO: Nitric oxide; cNOS: Constitutive isoforms of endothelial nitric oxide synthase or neuronal nitric oxide synthase; MDA: Malondialdehyde; GSH: Glutathione; SOD: Superoxide dismutase; GPx: Glutathione peroxidase; COX2: Cyclooxygenase 2; HIF: Hypoxia-inducible factor; DTNB: 5,5’-dithiobis (2-nitrobenzoic acid); CAT: Catalase.

Table 3 Effects of exercise on obese mice with colitis

Ref.	Diet	Model	Exercise	Outcomes
Mazur-Bialy et al[27]	HFD: 42% fat, 5495.855 kcal/kg; SD: 3518.05 kcal/kg	TNBS	VWR	Macroscopic parameters: Body weight (decreasing), mesenteric fat pad/body weight (decreasing), colonic blood flow (increasing), DAI (decreasing); Plasma level: TNF-α (decreasing), MCP-1 (decreasing), IL-6 (decreasing), IL-13 (decreasing), IL-17 (decreasing), IL-1α (decreasing), KC (decreasing), IL-4 (decreasing), leptin (decreasing), irisin (increasing), adiponectin (increasing); White adipose tissue: TNF-α (decreasing), IL-6 (decreasing), MCP-1 (decreasing), leptin (decreasing), adiponectin (increasing)
Wojcik-Grzybek et al[30]	HFD: 42% fat, 5495.855 kcal/kg; SD: 3518.05 kcal/kg	TNBS	VWR	Macroscopic parameters: Body weight (decreasing), grip strength test (increasing), DAI (decreasing); Colon parameters: MDA/4-HNE (decreasing), 8-OHdG (decreasing), GSH/GSSG (increasing), SOD (decreasing); Plasma level: IL-2 (increasing), IL-10 (decreasing), IL-17α (decreasing), MCP-1 (decreasing), IL-6 (decreasing), IL-12 p70 (decreasing), TNF-α (decreasing), leptin (decreasing)
Maillard et al[28]	High-fat and sugar diet: 13.2% proteins, 58.7% lipids, 28.1% carbohydrates(sucrose), 5317 kcal/kg	CEABAC10 transgenic mice + invasive Escherichia coli	VWR	Macroscopic parameters: Body weight (no change), mesenteric adipose tissue (decreasing); Plasma level: Active LPS (no change); Colon tight junction proteins: Occludin (increasing), ZO-1 (increasing); Fecal SCFAs: Propionate (increasing), butyrate (increasing), acetate (no change); Gut microbiota: Α-diversity (no change), β-diversity (increasing), Ruminococcus (increasing), Oscillospira (increasing)
Bilski et al[18]	HFD: 70% cholesterol; LFD: 10% cholesterol; SD: < 5% of total fat	Wistar rats with TNBS	FTR	Macroscopic parameters: Area of colonic lesions(decreasing), colonic blood flow (increasing), weight of colonic tissue (decreasing); Plasma level: IL-1β (decreasing), TNF-α (decreasing), TWEAK (decreasing), irisin (increasing), IL-6 (increasing); Colon parameters: MPO activity (decreasing), leptin (decreasing), adiponectin (increasing), IL-1β (decreasing), TNF-α (decreasing), HIF-1α (decreasing)
Bilski et al[19]	HFD: 42% fat	C57BL/6 TNBS	FTR	Macroscopic parameters: DAI (increasing), CBF (decreasing), histological score (increasing), energy intake (decreasing); Colon inflammatory parameters: TNF-mRNA (increasing), TNF-protein (increasing), IL-1 mRNA (increasing), IL-1 protein (increasing), IL-6 mRNA (increasing), IL-6 protein (increasing), IL-17 (increasing), IL-10 (increasing), IFN-γ (increasing); Colon oxidation and antioxidant parameters: MDA/4-HNE (increasing), GSH (increasing), SOD (increasing), HO-1 mRNA (no change), iNOS mRNA (increasing), COX2 mRNA (increasing), HO-1 protein (no change), HIF-1α protein (increasing)

All data were obese colitis + exercise vs obese colitis + sedentary. HFD: High-fat diet; LFD: Low-fat diet; SD: Standard diet; TNBS: Trinitro-benzene-sulfonic acid; FTR: Forced treadmill running; VWR: Voluntary wheel running; DAI: Disease activity index; TNF: Tumor necrosis factor; mRNA: Messenger RNA; IL: Interleukin; MCP-1: Monocyte chemoattractant protein-1; KC: Murine chemokine; MDA: Malondialdehyde; 4-HNE: 4-hydroxynonenal; 8-OHdG: 8-oxo-2’-deoxyguanosine; GSH: Glutathione; GSSG: Oxidized glutathione; SOD: Superoxide dismutase; LPS: Lipopolysaccharides; ZO-1: Zonula occludens-1; SCFAs: Short-chain fatty acids; TWEAK: Tumor necrosis factor-like weak inducer of apoptosis; MPO: Myeloperoxidase; HIF: Hypoxia-inducible factor; CBF: Cerebral blood flow; IFN: Interferon; HO-1: Heme oxygenase-1; iNOS: Inducible nitric oxide synthase; COX2: Cyclooxygenase 2.