Table 2.

Summary of animal studies on prebiotics in anemia.

Prebiotic/ Author	Dose	Type of Administration	Subject Study Group (n)/Control Group (n)	Assessment Method	Main Result
FOS; Lobo AR. et al., (2014) [39]	7.5% FOS for 1 or 2 weeks	yacon flour or Raftilose P95	iron deficient anemic rats supplemented with FP assigned to RAF group (n = 16) or YF (n = 16)/control group (n = 16)	HRE, hepatic Fe stores	FOS supplementation increased Fe bioavailability measured by HRE and hepatic Fe stores, which were more pronounced in the RAF group at week 1 changes in Hb level in FOS-fed rats were greater than those in the FP group (p = 0.01) and similar to those in the FS group
FOS, Ohta A. et al., (1998) [41]	75 g/kg for 6 weeks	added to diet	rats after surgically stomach removing (n = 7) or sham operated rats (n = 7) fed the FOS diet/no FOS diet (n = 7)	Ht, Hb concentration, HRE	Ht, Hb concentration, and HRE were significantly lower in gastrectomized rats fed a diet without FOS compared to the other three groups FOS prevented anemia in totally gastrectomized rats
FOS; Zhang F. et al., (2017) [40]	5% (w/v) FOS = 1–2/g per day for 28 days	dissolved in water	non anemic rats fed regular diet + FOS (n = 6)/regular no FOS diet (n = 6) anemic rats fed regular diet + FOS (n = 6)/regular no FOS diet (n = 6) anemic rats fed low iron diet + FOS (n = 6)/low-iron no FOS diet (6)	Hb concentration	anemic rats fed low-iron diet + FOS had higher Hb level (p < 0.05) after 21 days, compared to control group in anemic rats fed regular diet, Hb returned to normal level after 14 days and FOS supplementation showed no additional effects
Sc-FOS, inulin; Sakai K. et al., (2000) [42]	Sc-FOS (75 g/kg diet) or inulin (75/kg diet) for 6 weeks	with diet	gastrectomized rats fed sc-FOS diet (n = 5) or inulin diet (n = 5)/gastrectomized (n = 5) or sham operated (n = 5) rats fed control diet	Hb concentration, Ht, HRE	in gastrectomized rats Hb and Ht levels were significantly higher in the group fed the Sc-FOS-containing diet compared with levels in rats fed the control diet or the inulin-containing diet HRE after 3 weeks in the FOS diet group was significantly higher than HRE in the other groups
Sc-FOS; Sakai K. et al., (2000) [43]	Sc-FOS 75 g/kg diet for 28 days	with diet	sham-operated (n = 7)/GX (n = 7)/CX (n = 7)/GCX (n = 7) rats fed Sc-FOS diet (n = 7)/control diet (n = 7)	Ht, Hb and SI concentration, UIBC, Hb-Fe, HRE	Hb and Ht in the GX rats without cecectomy and fed the Sc-FOS diet were higher than those in the control group (p < 0.05) GX rats without cecectomy and fed the Sc-FOS diet had significantly higher UIBC and HRE compared with gastrectomized rats without cecectomy and fed the control diet the effectiveness of Sc-FOS in preventing postgastrectomy anemia was significantly decreased by cecectomy
Inulin; Mohammad O. et al., (2021) [48]	4% long or short-chain inulin by 4 weeks	in yogurt	anemic rats fed inulin free yogurt (n = 8) or yogurt containing long-chain inulin (n = 8) or short chain inulin (n = 8)/anemic (n = 8) or non-anemic (n = 8) rats fed inulin-free yogurt (n = 8)	Hb concentration, RBC, Ht, SI content	long-chain inulin exhibited the best effects in terms of iron supplementation and bioavailability
Inulin; Freitas K.C. et al., (2012) [49]	100 g/kg of ration by 21 days	with diet	anemic rats fed HP inulin (n = 12) or HP inulin + oligofructose (n = 12) or oligofructose (n = 11)/control diet (n = 12)	intestinal absorption of Fe, Hb concentration	HP inulin and oligofructose increased the intestinal absorption of Fe in rats values of Hb in the HP inulin were significant higher (p ≤ 0.001) than in the control group
inulin, FOS, GOS; Zhang F. et al., (2021) [50]	5% (m/V) (1–1.5 g/d) prebiotic by 35 dys	dissolved in water	45 u Fe/g diet (n = 8) or 12 u Fe/g diet (n = 8) + short-chain FOS + long-chain inulin (n = 8)/45 u Fe/g diet (n = 8) or 12 u Fe/g diet (n = 8) 12 u Fe/g diet + FOS (n = 8) or inulin (n = 8) or GOS (n = 8) or lactulose (n = 8)/12 u Fe/g diet (n = 8)	Hb concentration, tissue non-heme iron levels	Hb concentration in rats supplemented with GOS after 3 weeks was significantly higher than in rats without supplementation Hb concentration in rats supplemented with FOS after 4 weeks was significantly higher than in rats without supplementation inulin, lactulose, short chain FOS + long chain inulin showed no effect; prebiotics had no effects on rats with normal iron status
Pectin; Kim M. et al., (1992) [56]	80 g/kg diet	added to diet	group 1—pectin high DE and high MW (n = 6)/rats fed control diet (n = 6) group 2—pectin with high DE and low MW (n = 6)/rats fed control diet(n = 6) group 3—pectin with low DE and high MW (n = 6)/rats fed control diet (n = 6) group 4—pectin with low DE and low MW (n = 6)/rats fed control diet (n = 6) + pair fed rats: each rat was fed an amount of the control diet equal to the average consumed by its respective pectin-fed group on the previous day	HRE, MCHC, UIBC, TIBC, Ht, SI concentration	pectin did not reduce iron bioavailability rats from group 2 had higher (p < 0.05) HRE, Ht, SI concentration, transferrin saturation, and lower UIBC and TIBC compared with the control group rats from groups 1 and 4 had improved hematological indices compared with group 3 and the control group

FIA—fractional iron absorption, FS—ferrous sulphate, FP—ferric pyrophosphate, Ht—hematocrit, Hb—hemoglobin concentration, HRE—hemoglobin regeneration efficiency, SI -serum iron, UIBC—unsaturated iron-binding capacity, Hb-Fe—Hemoglobin-iron, Ascorbic Acid (AA), RAF—Raftilose, YF—yacon flour, GX—gastrectomy, CX—cecectomy, GCX—gastrectomy and cecectomy, MCHC—mean corpuscular hemoglobin concentration, DE—degree of esterification, HP inulin—high performance, MW—molecular weight, MCHC—mean corpuscular hemoglobin concentration, TIBC—total iron-binding capacity.