Table 1.
Summary behavioural studies.
| Study | Species | HMO Component and Dose | Age and Duration Administration | Age Test | Tests | Key Results |
|---|---|---|---|---|---|---|
| Fucosylated HMOs | ||||||
| Oliveros et al., 2016 [46] | Lister Hooded Rats | 2′-FL (1g/KG/BW) |
From PND 3–weaning | Long Term study: (1) 4–6 weeks (2) 1 year old |
NORT Y maze MWM LTP (only at 1 year) |
At 6 weeks of age no differences in behaviour (n = 12) were found. At 1 year of age, 2′-FL rats showed improved performance in the NORT and Y- maze paradigms. No effect was observed in the MWM. LTP was more intense and long lasting in the 2′-FL supplemented groups (n = 10) |
| Sprague Dawley Rats | 2′-FL (1g/ KG/BW) |
From PND3 until week 6 | Short Term study: 6 weeks |
LTP | LTP was more intense and long lasting in the 2′-FL supplemented groups (n = 10). | |
| Vazquez et al., 2016 [48] | Sprague Dawley Rats | 2′FL (350 mg/kg/BW via AIN-93M diet) L-Fucose (Fuc) (equimolar amounts of fuc and 2′-FL via AIN-93M diet) |
3–4.5 months old for 5 weeks | Started at 2.5–4 months old | Operant conditioning (FR1) LTP |
2′-FL but not fuc displayed enhanced LTP. Vagotomy inhibited the effects of oral 2′-FL on LTP (n = 10) and operant learning paradigms (n = 10). |
| Fleming et al., 2020a [52] | Pigs (1050 Cambro genetics) | Three groups: Oligofructose (OF) 5 g/L OF + 2′-FL 5 g/L OF + 1 g/L 2′-FL Control. Nothing |
PND 2–33 | PND 22 | NORT | Pigs (n = 12) who received Oligofructose (OF) displayed enhanced object recognition when tested 1 h after being habituated to the two objects. When pigs consumed both 2′-FL and OF, they showed improved recognition memory after a 48-h delay. |
| Fleming et al., 2020b [53] | Pigs (1050 Cambro genetics) | Four groups: HMOs (2′FL + LNnT) 1 g/L 2′-FL + 0.5 g/L LNnT BMOs 12.4 g/L HMOs + BMOs 1 g/L 2′-FL + 0.5 g/L LNnT + 12.4 g/L BMOs Control. Nothing |
PND 2–33 | PND 22 | NORT | Pigs (n = 12) who received only HMOs displayed enhanced object recognition when tested 1 h after being habituated to the two objects. When pigs consumed both HMOs and BMOs, they showed improved recognition memory after a 48-h delay. |
| Vazquez et al., 2015 [46] | Sprague Dawley Rats | 2′FL (1 g/kg/BW) via oral gavage during acute administration and 2′-FL (350 mg/Kg/BW) via AIN-93G diet, during short time feeding |
Acute administration: when rats were 3 months old Short-time feeding from 2.5–4 months, for 5 weeks |
Operant tests started when administration started. LTP was performed after administration period. |
Operant conditioning (FR1) LTP |
2′-FL groups performed better in operant learning paradigms (rats n = 10, mice n = 28) and showed an enhanced LTP response (rats and mice n = 8). The long-time supplementation of 2′FL also increased the expression of molecules involved in storage newly acquired memories (BDNF, PSD-95 phosphorylated CamKII, etc.) |
| C57BL/6 mice | 2′FL (350 mg/Kg/BW via AIN-93G diet) | Long-time feeding from 2–3.5 months old, for 12 weeks | Intellicage (FR1, FR4, FR8) LTP |
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| Sialylated HMOs | ||||||
| Oliveros et al., 2018 [47] | Sprague Dawley Rats | Neu5Ac 6′-SL (Dose ranged from 400 mg/Kg/BW to 2600 mg/Kg/BW based on theoretical model) |
From PND 3 until weaning | After weaning | NORT Y maze |
No effects detected after weaning (n = 10). At 1 year old, sia (Neu5Ac and 6′-SL) exposed rats (n = 8♀) showed improved performance on all the behavioural tests (NORT, Y-maze, Intellicage) and showed enhanced LTP (n = 10) when compared to the control group. Of the SL supplemented animals, the 6′-SL group performed better than the Neu5AC group |
| 1 year old | NORT Y maze Intellicage LTP |
|||||
| Wang et al., 2007 [50] | Piglets Landrace/Large White cross | Sialic Acid (ingredient of Casein glycomacropeptide cGMP)) (4 groups of animals with their own dose each; 0 mg/L (control), 140 mg/L; 300 mg/L; 635 mg/L and 830 mg/L) |
From PND 3 until end of experiment | PND 21–PND 35 | 8-arm Radial maze | Supplemented groups (n = 12–14 per group) required less trials to learn the required response, with a dose–response correlation for the difficult task. |
| Obelitz-Ryom et al., 2019 [51] | Pre-term delivered (experimental groups) Piglets Landrace x Yorkshire x Duroc | Sialyllactose (6′-SL + 3′-SL) (380 mg/L) Lactose (control) (6000 mg/L) |
PND1–PND19 | PND13–PND18 | Spatial T-maze | Four experimental groups were included in the study; PRE-SAL (n = 10 ♀, 10 ♂), PRE-CON (n = 9 ♀, 11 ♂), TERM-CON (n = 9 ♀, 5 ♂) and TERM-SAL (n = 6 ♀, 6 ♂). TERM CON piglets reached learning criteria of 80% correct choices on day 3, PRE-SAL on day 4 and PRE-CON on day 5. More PRE-SAL piglets reached the T maze learning criteria compared to PRE-CON piglets. Upregulation of genes for sialic acid metabolism, myelination and ganglioside biosynthesis were present in the hippocampus of SL supplemented preterm piglets. |
| Term delivered piglets (reference groups) Landrace x Yorkshire x Duroc |
Lactose (control) (6000 mg/L) Pig’s milk (under natural rearing conditions) |
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| Fleming et al., 2018 [54] | Piglets (no breed specified) |
Sialyllactose (380 mg/L) | PND2–PND22 | PND15–PND22 | NORT | No effects (n = 17) were observed. |
NORT: Novel Object Recognition Test, MWM: Morris Water Maze, LTP: Long-Term Potentiation. BMO: Bovine Milk Oligosaccharide. When provided, strains of species have been included in the table. In all studies presented here, the HMOs were administered orally. All animals used in the studies were male, unless otherwise specified. When the experimental groups have not been detailed in the key results column, the reported n indicates the number of animals per experimental group of that study.