Table 2.

Overview of the therapeutic effects of B. breve on NDDs

Disease	Research types	Strain	Model	Dose	Key effects	Ref
AD	in vivo	B. breve MCC1274	AppNL-G-F mice	1×109 CFU/mouse for 4 weeks	- Improvement in cognitive function - Reduction in Aβ accumulation and neuroinflammation in the brain - Increase in synaptic protein expression in the brain	Abdelhamid et al., 2024
	in vivo	B. breve HNXY26M4	APP/PS1 Mice	1×109 CFU/mouse for 12 weeks	- Improvement in cognitive function - Alleviation of neuroinflammation and synaptic dysfunction - Restoration of gut microbiota balance	Zhu et al., 2023
	in vivo	B. breve MCC1274	APP Knock-In mice	1×109 CFU/mouse for 4 months	- Increase in antioxidant-active metabolites in plasma - Increase in glutathione-related metabolites in plasma	Ohno et al., 2022
	in vivo	B. breve MCC1274	Wild type mice	1×109 CFU/mouse for 4 months	- Reduction in Aβ42 levels and tau phosphorylation in the brain - Activation of the AKT/GSK-3β pathway in the brain - Inhibition of neuroinflammation	Abdelhamid et al., 2022a
	in vivo	B. breve MCC1274	APP Knock-In mice	1×109 CFU/mouse for 4 months	- Improvement in memory impairment - Inhibition of Aβ accumulation - Activation of the ERK/HIF-1α signaling pathway - Inhibition of neuroinflammation	Abdelhamid et al., 2022b
	in vivo	B. breve MCC1274	Aβ-Injected mice	1×109 organisms/mouse for 11 days	- Improvement in cognitive function - Inhibition of gene expression related to inflammation and immune responsiveness in the brain	Kobayashi et al., 2017
	RCT	B. breve MCC1274	Older patients with MCI	2×1010 CFU for 24 weeks	- Improvement in the "orientation" subscale of ADAS-Jcog - Improvement in the "orientation in time" and "writing" subscales of MMSE	Asaoka et al., 2022
	RCT	B. breve MCC1274	Older patients with MCI	2×1010 CFU for 16 weeks	- Total RBANS scores are correlated with hemoglobin A1c levels.	Bernier et al., 2021
	RCT	B. breve MCC1274	Older patients with MCI	2×1010 CFU for 16 weeks	- Increase in total RBANS scores - Increase in scores of immediate memory, visuospatial/constructional, and delayed memory in both intention-to-treat analysis and per-protocol analysis	Xiao et al., 2020
	RCT	B. breve MCC1274	Older adults with memory comlaints	2 capsules (1×1010 CFU/capsule) for 12 weeks	- Increase in the 'immediate memory' subscale of RBANS and MMSE	Kobayashi et al., 2019b
	Clinical trials	B. breve MCC1274	Older patients with MCI	2 capsules (2×1010 CFU/capsule) for 24 weeks	- Increase in MMSE scores - Increase in POMS2 and GSRS scores	Kobayashi et al., 2019a
PD	in vivo	B. breve Bif11	MPTP-injected rats	1 or 2×1010 CFU/mouse for 21 days	- Improvement in cognitive and motor functions - Protection of neurons and inhibition of neuroinflammation - Restoration of SCFAs in the gut and reduction of intestinal permeability	Valvaikar et al., 2024
	in vivo	B. breve CCFM1067	MPTP-injected mice	1.0×109 CFU/mL (0.2 mL/mouse) for 33 days	- Protection of neurons and inhibition of neuroinflammation - Alleviation of oxidative stress and mitigation of BBB damage - Restoration of gut microbiota balance	Li et al., 2022
	in vivo	B. breve MCC1274	MPTP-injected mice	1×109 organisms/mouse for 4 days	- Recovery of facilitation of contextual fear extinction - Enhancement of synaptic plasticity in the brain - Reduction of neuropsin levels in the brain	Ishii et al., 2021
MS	in vivo	B. breve PTCC1367	Cuprizone-induced rats	2×109 CFU/mouse for 28 days	- Improvement in cognitive function - Alleviation of oxidative stress and demyelination	Hasaniani et al., 2024

AD, Alzheimer’s disease; B. breve, Bifidobacterium breve; APP/PS1, amyloid precursor protein and mutant human presenilin 1; CFU, colony forming unit; Aβ, Amyloid β; APP, Amyloid precursor protein; AKT, Protein kinase B; GSK-3β, glycogen synthase kinase-3β; ERK, Extracellular signal-regulated kinase; HIF-1α, Hypoxia Inducible Factor 1α; RCT, Randomized controlled trial; MCI, Mild cognitive impairment; ADAS-Jcog, Alzheimer Disease Assessment Scale (Japanese version) cognitive subscale; MMSE, Mini-Mental State Examination; RBANS, Repeatable Battery for the Assessment of Neuropsychological Status; POMS2, Profile of Mood States 2nd Edition; GSRS, Gastrointestinal Symptom Rating Scale; PD, Parkinson’s disease; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; SCFAs, Short-chain fatty acids; BBB, Blood-Brain Barrier; MS, Multiple sclerosis.