Table 1.
A summary of prebiotic interventions among animals to evaluate their effectiveness in altering mineral absorption, bone health outcomes, and intestinal parameters
| Prebiotic/substance | Treatment dose and duration | Study design | Animal model description | Measures/analyses | Findings | Abbreviated reference |
|---|---|---|---|---|---|---|
| Anoectochilus formosanus (AF), inulin | 4 diets: control, 200 mg/kg AF, 400 mg/kg AF and 400 mg/kg inulin, for 12 weeks | Parallel design with 5 groups: OVX or SHAM on control diet + water; remaining 3 OVX groups randomly assigned to supplemented diets; AF delivered as aqueous solution | Female Wistar rats (n = 40), age 3 months | Apparent Ca absorption and retention; tibia BMD/BMC; bone-breaking strength of femur; trabecular bone microarchitecture; fecal microbial culture assessments; cecum morphology, SCFA and pH | 400 g/kg AF and 400 g/kg inulin resulted in greater apparent Ca absorption and retention, cecal wall weight and lower cecal pH, greater total fecal SCFA and butyrate, as well as improved biomechanical properties of bone and decreased bone turnover; AF improved fecal bifidobacteria content | Yang L, et al. 2013 (Ref. 78) |
| Difructose anhydride III (DFAIII) | 0 or 15 g/kg DFAIII, for 4 weeks | Parallel design; rats divided into 4 groups (2 groups of OVX and 2 groups of SHAM rats) and randomly assigned to control (AIN93G) or vitamin D-deficient diets for 8 weeks; at 11-weeks of age, the 4 groups were further divided into DFAIII groups | Female OVX Sprague Dawley rats (n = 64), age 3 weeks | Apparent Ca absorption and retention; femur Ca, Mg and P content; intestinal Ca transporter expression; cecum morphology, pH and SCFA content | Serum Ca concentration and calbindin D9k mRNA levels were affected by vit-D-deficient diets; Ca absorption rates in vit-D-deficient groups were much lower than any other group; DFAIII increased Ca absorption rates in both SHAM and OVX groups, but the effect was higher in the OVX rats; femoral Ca content was significantly lower in the vit-D-deficient group in both SHAM and OVX but DFAIII increased femoral Ca content over other groups; femur Mg content was higher in the DFAIII-vit-D-deficient SHAM rats; femoral P content was influence by vit-D deficiency and OVX but not DAFIII; cecal weight was affected by vit-D deficiency, OVX and DFAIII diet; cecal pH decreased while total SCFA increased with DFAIII diets | Mitamura R, et al. 2006 (Ref. 106) |
| FOS | 0 or 5% FOS, for 23 days | Parallel design; AIN-93G used as base diet with 7.5 g/kg Ca; FOS replaced sucrose in the diet | Male Wistar rats (n = 16), age 4 weeks | Apparent Ca and Mg absorption for 5 day intervals starting at days 4, 10 and 16; femur and tibia BMD by DXA; bone biomechanical properties; cecal weight and pH | Ca and Mg absorption and retention were greater with FOS compared to control at all three measurement time points even though the percentage of Ca and Mg absorbed decreased over time; femur and tibia Ca content were greater in the FOS group; no difference in BMD between the two groups; peak breaking force of femur improved with FOS; cecal wall and content weights were greater in FOS group and cecal pH was lower with FOS | Lobo A, et al. 2006 (Ref. 113) |
| FOS | 0 or 5% FOS, for 15 days | Parallel design, SI; rats were pair-fed to match dietary intake; FOS consisted of 34% 1-ketose, 53% nystose and 10% 1F-b-fructofuranosyl nystose; diet run-in for 6 days; FOS replaced dietary sucrose | Male Wistar rats (n = 16), age 45 days | Apparent and true Ca absorption and kinetics | FOS increased both true Ca absorption and Ca balance relative to controls; no differences in bone formation or resorption were observed; urinary Ca excretion in FOS group was significantly greater than in controls; Ca balance in FOS group was correlated with Ca absorption | Morohashi T, et al. 1998 (Ref. 109) |
| FOS | 0 or 50 g FOS/kg of diet, for 28 days | Parallel design; sham and cecectomized rats received both diets | Male Sprague Dawley rats (n = 28), age 5 weeks | Apparent Ca and Mg absorption; cecal pH and fecal SCFA concentrations | FOS improved both Ca and Mg absorption in the sham animals but only Mg in the cecectomized rats; FOS decreased cecal and colonic pH and altered the composition of SCFA | Ohta A, et al. 1994 (Ref. 107) |
| FOS | 0 or 50 g FOS/kg of diet, for 8 days | Parallel design; 1 week dietary run-in on control diet | Male Sprague Dawley rats (n = 28) 6-week-old | Apparent Ca and Mg absorption | Ca and Mg absorption increased across the colon and rectum | Ohta A, et al. 1995 (Ref. 110) |
| FOS | 100 g/kg FOS or sucrose by weight of diet, for 10 days | Parallel design; 3 study groups: sham-operated rats on control diet and gastrectomized rats distributed into each treatment group | Male Sprague Dawley rats (n = 17), age 4 weeks | Apparent Ca, P and Mg absorption; Ca transporter quantification by western blots | FOS-supplemented gastrectomized rats experienced improvements in apparent Mg absorption relative to gastrectomized and sham controls; FOS + gastrectomy resulted in greater P absorption relative to sham but not gastrectomized controls; Ca absorption was improved in FOS + gastrectomy rats compared to gastrectomized but not sham controls; FOS + gastrectomized rats had greater cecal mucosa wet weight and presence of calbindin D9k in the distal small intestine, cecum and colon | Ohta A, et al. 1998 (Ref. 84) |
| FOS | 0, 50 or 100 g/kg FOS, for 10 days | Parallel design; control diet contained 100 g/kg sucrose | Male Sprague Dawley rats (n = 18), age 5 weeks | Apparent Ca absorption; total and calbindin D9k protein expression by Western blot | Ca absorption increased dose-dependently with FOS; small intestinal and cecal weight increased with FOS; calbindin D9k concentration was significantly increased in the cecum on the 10% FOS treatment compared to 5% FOS | Ohta A, et al. 1998a (Ref. 101) |
| FOS | 5 and 10% nystose, 5 and 10% kestose, 5 and 10% FOS, 24 days | Parallel design; 7 study diets with control diet containing 100 g/kg sucrose, all prebiotic diets contained 50 g/kg sucrose | Male Sprague Dawley rats (n = 49), age 5 weeks | Apparent Ca and Mg absorption at 10 and 24 days | Each prebiotic treatment increased Ca and Mg absorption dose-dependently after 10 days but not at 24 days; 10% FOS decreased fecal Ca excretion and increased urinary Ca excretion; apparent absorption of Ca in rats on 10% FOS was higher that control rats; fecal Mg excretion decreased with 10% FOS while urinary Mg excretion increased with 10% FOS; apparent absorption of Mg was higher than controls for both 5 and 10% FOS | Ohta A, et al. 1998b (Ref. 103) |
| FOS | 0 or 5 g FOS/100 g diet, for 15 days | Parallel design; control diet was AIN-93; FOS replaced dietary sucrose; run-in diet for 3 days before intervention; Ca content of both diets was ~ 5.2 g/kg of diet | Male Wistar rats (n = 16), age 45 days | Apparent and fractional Ca and Mg absorption; femur microarchitecture | Apparent and fractional Ca and Mg absorption were increased with FOS relative to controls; trabecular bone volume in the distal metaphysis and bone volume in the femoral neck were greater with FOS; bone area of the mid-femur did not differ; significant positive correlation between absorbed Ca and femoral Ca content | Takahara S, et al. 2000 (Ref. 112) |
| FOS and soy isoflavones (IF) | 0 or 7.5% FOS with 0, 10, 20, 40, or 80 µg/g body weight of IF, for 90 days | Parallel design; 12 study groups including sham and OVX controls with and without FOS; short-chain FOS given at 2.5% for week 1, 5% for week 2 and at 7.5% for remainder of 3 months | Female OVX Wistar rats (n = 96), age 3 months | BMD and body composition by DXA; femur biomechanical properties; bone biomarkers | FOS enhanced the bone-sparing effects of IF by increasing femur BMD and bone strength (femur failure load); FOS addition did not significantly alter osteocalcin and deoxypyridinoline concentrations | Mathey J, et al. 2004 (Ref. 115) |
| FOS and soy isoflavones (IF) | 5% FOS, 0.2% IF, 5% FOS + 0.2% IF, for 6 weeks | Parallel design; 2 week adaptation period before surgery; diet treatments began 7 days post-OVX; control diet was AIN-93G with corn oil replacing soybean oil | Female OVX ddY mice (n = 64), age 8 weeks | BMD and BMC by DXA; femur BMC by pQCT; femur Ca, Mg, and P content | Relative to OVX controls, IF and FOS + IF increased BMD of the middle and distal femur while FOS + IF increased BMD of the proximal femur; FOS + IF increased trabecular BMD of the femur compared to control and FOS alone; IF improved femur mineral content | Ohta A, et al. 2002 (Ref. 117) |
| FOS from yacon flour + Bifidobacterium longum | 15.6 g yacon flour/100 g of diet, for 28 days | Parallel design; control diet consisted on AIN-93G; 4 diets: control, yacon flour, control + B. longum, yacon flour + B. longum; yacon flour contains 4% FOS | Male Wistar rats (n = 32) | Bone biomechanical properties; mineral content (Ca, P, Mg); cecal morphology, pH and SCFA content; bifidobacteria, lactobacillus and total anaerobes quantified | Both control + B. longum and yacon + B. longum resulted in greater tibial Ca, Mg and P content relative to control; Ca and Mg were also higher in the yacon + B. longum groups compared to yacon only; peak breaking force did not differ; cecal weight was greatest with the yacon diet and was also greater in yacon + B. longum compared to control; cecal propionate content was greater in all treatments compared to control; cecal weight and total anaerobes were highest with yacon diet | Rodrigues F, et al. 2012 (Ref. 56) |
| FOS, dried plum, soy | 5% FOS, for 60 days | Parallel design with 6 groups: sham-operated and OVX (OVX) groups served as controls consuming casein, remaining 4 OVX groups consumed all other non-casein diets; 45 day run-in on standard diet following OVX; 5 diets: casein-based diet (casein), soy-based diet (soy), soy-based diet with dried plum at 7.5% (soy + plum), FOS at 5% (soy + FOS), and combination of dried plum and FOS (soy + plum + FOS) | Female OVX Sprague Dawley rats (n = 72), age 3 months | Bone biomarkers; femoral strength; DXA; histomorphometry of tibia | Higher whole-body BMD was observed in rats from soy + FOS, soy + plum, and soy + plum + FOS groups; soy + FOS increased peak breaking force of the femur more than any other treatment; reductions in bone resorption (deoxypyridinoline) and increases in alkaline phosphatase were greatest for soy diets with plum, FOS and plum + FOS relative to controls | Johnson C, et al. 2011 (Ref. 55) |
| FOS, soy | 5% FOS, for 4 months | Parallel design with 5 groups: sham-operated and OVX groups served as controls, remaining 3 OVX groups consumed soy-based diet (soy), FOS-supplemented diet (FOS), or soy-based plus FOS (soy + FOS); 3 month run-in on standard diet following OVX | Female Sprague Dawley rats (n = 63), age 9 months | BMD and BMC by DXA; bone biomechanical and microarchitectural analysis | Whole-body BMD was higher in FOS and soy + FOS groups; FOS and soy + FOS diets improved lumbar BMC and BMD; soy + FOS was most effective at increasing trabecular number and decreasing trabecular separation when compared to OVX controls; femur biomechanical measures were not changed by any diet | Devareddy L, et al. 2006 (Ref. 54) |
| GOS | 0 or 5% GOS, for 30 days | Parallel design; both diets fed to sham and OVX animals; AIN-76 diet used with GOS replacing sucrose | Female OVX Wistar rats (n = 36), age 4 weeks | Apparent Ca absorption; femur and tibia Ca content; cecal pH, wall and content weights; fecal SCFA concentrations | GOS improved Ca absorption at 8–10 days and 18–20 days relative to control OVX animals but this effect disappeared by 28–30 days; among the OVX group, GOS only improved tibia Ca content; cecal content and wall weight were increased by GOS and cecal pH was reduced; total SCFA and acetate, propionate, butyrate and succinate were increased with GOS treatment | Chonan O, et al. 1995 (Ref. 24) |
| GOS | 5 g GOS/100 g of diet, for 30 days | Parallel design, SI; rats were acclimated to their assigned calcium intake for 30 days prior to GOS feeding; diets based on AIN-76 formulation; 4 diets: normal-Ca (0.5 g/100 g), low-Ca (0.05 g/100 g), and normal and low Ca with the addition of 6′-GOS | Male Wistar rats (n = 32), age 4 weeks | Apparent Ca absorption; femoral and tibia Ca content; cecal morphology and SCFA content | GOS was more potent than control diet at stimulating Ca absorption with normal-Ca diet after 8–10 and 18–20 days, but this effect did not persist through 28–30 days; femur and tibia Ca content were higher in rats fed GOS + normal-Ca diet; Ca absorption and bone Ca content were not affected by GOS when combined with a low-Ca diet; GOS feeding increased, cecal tissue and content weights, total SCFA and acetic, propionic and butyric acid content on both low and normal-Ca diets | Chonan O, et al. 1996 (Ref. 25) |
| GOS | 0, 2, 4, 6 or 8% of GOS by weight of diet, for 8 weeks. | Parallel design, SI; dietary adaptation with AIN 93-G for 12 days; GOS replaced cornstarch in diet | Male Sprague Dawley rats (n = 75), age 4 weeks | Apparent absorption/retention of Ca and Mg; femur Ca uptake and micro-CT; cecal morphology, pH, wall and content weights; PCR-DGGE and bifidobacteria qPCR | Dose-dependent increases in net Ca and Mg absorption and retention, greater femur Ca uptake, vBMD and breaking force; dose-dependent increase in cecal wall and content weights and decreased cecal pH; PCR-DGGE profiles suggested differences in bacterial community structure and greater bifidobacteria by qPCR | Weaver C, et al. 2011 (Ref. 26) |
| GOS, Bifidobacteria bifidum and longum | 0, 12, 50 and 100 g/kg GOS, for 30 days | Parallel design; control diet was follow-up infant formula; all other treatments were infant formula plus probiotic and/or prebiotic; 8 diets: control, probiotic (bifidobacteria), prebiotic at 3 GOS intakes, and synbiotic (GOS + bifidobacteria at 3 GOS intakes) | Male Sprague Dawley rats (n = 54), age 3 weeks | Apparent mineral absorption and retention (Ca, Mg and P) at 8–10, 18–20 and 28–30 days | Infant formulas supplemented with 100 g/kg GOS and 50 and 100 g/kg synbiotic treatments were most effective at increasing Ca, Mg and P bioavailability compared to control; apparent absorption and retention of Ca, Mg and P were initially above 80% but decreased at later measurement time points | Pérez-Conesa D, et al. 2006 (Ref. 57) |
| GOS, Bifidobacteria bifidum and longum | 0, 12, 50 and 100 g/kg GOS, for 30 days | Parallel design; control diet was follow-up infant formula; all other treatments were infant formula plus probiotic and/or prebiotic; 8 diets: control, probiotic (bifidobacteria), prebiotic at 3 GOS intakes, and synbiotic (GOS + bifidobacteria) at 3 GOS intakes | Male Sprague Dawley rats (n = 54), age 3 weeks | Ca, Mg and P content of femur and tibia; cecal/colon morphology and pH | Femur and tibia Ca and P were improved most with prebiotic and synbiotic treatments; femur Mg content was reduced with all treatments relative to control while tibia Mg was unaffected; cecal wall weight was greater and pH lower with 100 g/kg GOS and synbiotic diets compared to control; synbiotic diets decreased colonic pH relative to control; colonic pH was negatively correlated with proximal and distal colon crypt depth and with distal colon cell density | Pérez-Conesa D, et al. 2007 (Ref. 58) |
| GOS, FOS | 5.3% GOS–FOS mix, for 50 days | Parallel design; 4 diets: normal-Ca diet (AIN 93-G + 0.5% Ca), low-Ca diet (AIN 93-G + 0.3% Ca), normal-Ca diet + 5.3% GOS + FOS, or low-Ca diet + 5.3% GOS + FOS; GOS and FOS were fed in a 9:1 ratio | Male Wistar weanling rats (n = 32) | Apparent Ca absorption; BMD and BMC by DXA; tibia histomorphometry; fecal lactobacillus colony assessment; cecal morphology and pH; femur biomechanical analysis | Femur Ca and P content was significantly higher among GOS + FOS groups; GOS + FOS groups resulted in greater tibia length than other diets; lactobacillus colonies were also increased with GOS + FOS; GOS + FOS groups had greater cecum weight and lower cecal pH | Bryk G, et al. 2015 (Ref. 53) |
| Inulin | 0, 3.75 and 7.5% inulin, for 3 weeks | Parallel design, SI: 4 age groups with control and treatment groups at each age; control diets included AIN 1993 mineral and vitamin mix; first 4 days at 3.5% inulin followed by 7.5% inulin | Male Wistar rats (n = 80), age 2.5, 5, 10, and 20 months | Fractional Ca and Mg absorption; cecal wall and content weights, pH and SCFA content | Inulin increased Ca and Mg absorption at all age groups but 10- and 20-month-old rats absorbed less Ca and Mg than younger rats; Ca and Mg retention decreased with age; cecal wall and content weights increased with a decrease in cecal pH at all inulin intakes; inulin also increased individual and total SCFAs relative to control | Coudray C, et al. 2005 (Ref. 100) |
| Inulin | 0 and 10% inulin, for 40 days | Parallel design; run-in on semi-purified diets until 10 weeks of age; 6 diets: 0% inulin + 0.25% Ca, 0% inulin + 0.5% Ca, 0% inulin + 0.75% Ca, 10% inulin + 0.25% Ca, 10% inulin + 0.5% Ca, 10% inulin + 0.75% Ca | Male Wistar rats (n = 60) | Apparent Ca and Mg absorption at days 13 and 36; cecal pH and SCFA content | Ca and Mg absorption increased with all inulin treatments; inulin effects on Ca absorption were greatest with low and high-Ca diets in the short-term but persisted only for the low-Ca diet in the long-term; inulin also lowered cecal pH and increased cecal weight; inulin improved cecal SCFA content and total SCFA was greatest in the 10% inulin + 0.25% Ca diet compared to 10% inulin + 0.75% Ca | Coudray C, et al. 2005 (Ref. 91) |
| Inulin | 3.75 and 7.5% inulin, for 26 days | Parallel design, SI; 8 study groups by age category and treatment group; first 4 days was 3.75% inulin followed by 7.5% inulin | Male Wistar rats (n = 80), age 2, 5, 10 and 20 months | Zn and Cu absorption; cecal morphology, SCFA content and pH determined | 7.5% inulin increased cecal wall and content weights, and decreased cecal pH; while Zn and Cu excretion increased and retention decreased with age, inulin increased Zn and Cu retention; Zn absorption correlated with cecal acetate, propionate and total SCFA; bone Zn increased with increasing age but was not affected by inulin intake; bone Cu did not vary by inulin intake or age | Coudray C, et al. 2006 (Ref. 104) |
| Inulin | 7.5% inulin, for 3 months | Parallel design; control diet designed to reflect “western diet”; 2 week run-in for dietary adaptation; measures at 1 and 3 months post-inulin diets; 4 diets: control, native inulin, reformulated inulin (combination of short- and long-chain fructans), dehydrated chicory | Male Wistar rats (n = 40), age 3 months | Apparent Ca and Mg absorption; BMD and BMC by DXA; bone biomarkers; femur biomechanical properties; cecal morphology, pH and SCFA content | Ca absorption increased with inulin at 1 month but the effect disappeared by 3 months; Mg absorption was improved at both 1 and 3 months; BMC was increased only with chicory inulin; BMD of diaphysis was improved by the chicory treatment but all other measures of bone strength or turnover were not different; inulin diets improved SCFA production with the chicory diet increasing propionate more than other inulin treatments | Demigné C, et al. 2008 (Ref. 114) |
| Inulin | 7% inulin solution (v/w) | Parallel design; 4 diets: gluten-free diets with either the appropriate Ca content or reduced Ca content, or gluten-free diets with adequate or reduced Ca plus inulin | Male Wistar rats (n = 32), age 4 weeks | Ca, Mg, and P balance; fecal SCFA concentration; microbial community analysis by PCR-DGGE and quantitative rt-qPCR of 16S rRNA gene | Diets with inulin resulted in increased mineral absorption; Ca content of the diet influenced Ca, P, and Mg absorption; inulin stimulated fecal bifidobacteria content when dietary Ca was adequate; SCFA content in cecum was influenced by interaction between dietary Ca and inulin | Krupa-Kozak U, et al. 2017 (Ref. 92) |
| inulin | 0, 5, 10 and 20% inulin, for 21 days | Parallel design | Male Wistar rats (n = 24), age 6 week | Apparent Ca absorption, cecal pools of Ca, P and Mg; cecal wall and content weights, pH and SCFA content | Inulin increased the cecal pool of Ca and P and to a lesser degree Mg; absorption of Ca was improved in a dose-dependent manner; total SCFA increased with inulin treatment; propionate content was increased with 10% inulin treatment relative to control | Levrat M, et al. 1991 (Ref. 99) |
| Inulin | 10% inulin, for 15 days | Parallel design; rats were stratified based on body weight; run-in diet for 7 days prior to treatments which were modified from AIN-93G diet; 4 diets: 15% soy bean oil (SO), 15% Soy bean oil + EPA + DHA (FSO), 15% SO + 10% Synergy1® or 15% FSO + 10% Synergy1® | Male Wistar rats (n = 24), age 6 week | Apparent mineral absorption and balance for Ca, Mg, Cu, Fe and Zn; bone mineral and biomechanical assessments (bone breaking); tibia and femur Ca and Zn content; tibia strength measures; cecal morphology and pH | Inulin improved apparent mineral absorption of Ca, Mg, Cu, Fe and Zn but FO and SO appeared to differentially influence absorption; FO negatively affected Mg absorption, while FSO potentiated the effects of inulin for Ca absorption and balance, and Cu, Fe and Zn absorption; bone Ca and Zn content were enhanced most by FSO + inulin; compared with controls, inulin increased cecal weight, number of crypts and cell density, and decreased cecal content pH | Lobo A, et al. 2009 (Ref. 111) |
| Inulin | 10% inulin, for 22 days | Various parallel design experiments following animal feeding: Using chamber experiments for Ca flux following treatment with varying Ca doses, SCFA, intestinal pH and inulin exposures; Synergy1® as inulin type | Male Sprague Dawley rats (n = 48) | Ca flux across excised intestinal tissue; morphological features of cecal and colonic tissue | Inulin increased Ca absorption in cecum; inulin altered gene expression of calbindin D9k, TRPV6 and Na–Ca co-transporters; inulin lowered cecal pH and increased cecal and colon content and wall weights; inulin increased intestinal SCFA content; pH alone had no influence on Ca absorption | Raschka L, et al. 2005 (Ref. 79) |
| Inulin | 0, 5, or 10 g inulin/100 g of diet, for 22 weeks | Parallel design; Inulin diets in combination with 0.2, 0.5, 1.0 g Ca/100 g of diet | Male Wistar rats (n = 108), age 4 weeks | Whole-body BMC and BMD by DXA at 0, 10, 14, 18 and 22 weeks | 5 g/100 g inulin had the greatest impact on whole-body BMC and BMD compared to control; BMC and BMD were improved by inulin at all Ca and age levels; bone area was differentially influenced by age and Ca | Roberfroid M, et al. 2002 (Ref. 96) |
| Inulin and polydextrose | 5% inulin or polydextrose, for 4-weeks | Parallel design, SI; 2 month stabilization period with non-purified diet post-OVX; 6 groups: OVX + control diet (AIN-93M), sham + control diet, OVX + biweekly estradiol injections, remaining 3 groups were 5% inulin from Synergy1® (SYN), 5% inulin from Fruitafit HD® (FRT), or 5% polydextrose (PDX) | Female Sprague Dawley rats, age 5 months | Mineral content of diet, fecal and urine samples; BMD by DXA | Among OVX groups there were no differences in BMD due to fiber treatment; OVX + SYN, FRT, or PDX increased net Mg absorption and retention; OVX + PDX group showed a significant increase in Ca absorption and utilization; OVX + SYN group resulted in an increase in cecal wall weight, SCFA production and chronic Ca absorption; OVX + FRT group demonstrated higher cecal wall weight than SHAM-CON but not OVX-CON | Legette L, et al. 2012 (Ref. 97) |
| Inulin and soy isoflavones (IF) | 0 mg/g inulin, 8 mg/g IF, or 50 mg/g + 8 mg/g inulin and IF, for 21 days | Parallel design; SI; control diet was AIN-93G; inulin and IF replaced cornstarch in diets | Male Sprague Dawley rats (n = 48), age 6 weeks | Ca absorption; femoral Ca content | Ca absorption and femoral Ca were significantly increased with IF compared to inulin; inulin + IF did not have an added benefit for Ca absorption or femoral content | Zafar T, et al. 2004 (Ref. 116) |
| Inulin, agave fructans | 10% inulin, 10% agave fructan 1 (CAF1), 10% agave fructan 2 (CAF2), for 6 weeks | Parallel design with 5 groups: OVX or sham on control diet; remaining 3 OVX groups randomly assigned to supplemented diets; CAF1 and 2 derived from Agave tequilana with average DP of 22 and 13, respectively | Female C57BL/6J mice (n = 48), age 12 weeks | Apparent Ca and Mg absorption; bone biomarkers; femur microarchitecture; cecal and colon morphology; fecal SCFA content | Ca absorption but not Mg absorption increased with all fructan treatments at 3 and 6 weeks; Ca and Mg content of bone was improved on all fructan treatments; P content also increased relative to control treatments; osteocalcin increased with fructan treatment; cecal and colonic SCFA production did not differ | García-Vieyra M, et al. 2014 (Ref. 80) |
| Inulin, FOS | 0 or 50 g/kg inulin + FOS mix, for 21 days | Parallel design, SI; control diet was AIN-93 with inulin + FOS replacing equal amounts of cornstarch and sucrose; run-in AIN-93 diet for 3 months following OVX | Female OVX Sprague Dawley rats (n = 26), age 6 months | True Ca absorption and kinetics; femur BMD and BMC by DXA | Inulin + FOS increased Ca absorption and retention compared to controls; inulin + FOS decreased bone turnover and improved bone Ca content; no differences were observed in bone-breaking strength | Zafar T, et al. 2004 (Ref. 105) |
| Inulin, soy isoflavone (genistein) | 0 or 5% inulin, for 4 weeks | Parallel design, SI; 6 treatment groups: sham and OVX controls, OVX + daily estradiol injections, and remaining OVX groups with genistein, ITF or both; control diet was AIN-93M; 4 diets: control, 200 ppm genistein, 5% Synergy1®, 200 ppm genistein + 5% Synergy1® | Female OVX Sprague Dawley rats (n = 96), age 5 months | Ca balance and kinetics; femur and tibia BMD by underwater weighing; bone pQCT; femur and tibia biomechanical properties and Ca content; cecal SCFA content | Inulin improved Ca absorption; genistein improved total and trabecular BMD of the distal femur; rats consuming genistein + inulin experienced greater bone formation and resorption rates | Legette L, et al. 2011 (Ref. 118) |
| Lactose | 0 or 10% lactose, for 6 weeks | Parallel design; 4 diets: vit-D-deficient; vit-D-deficient + 0.5% Ca + 0.3% P, vit-D-deficient + 1.5% Ca + 0.9% P + 15% lactose, and normal diet containing vit-D. 0.5% Ca + 0.3% P | Male Wistar rats (n = 26) resulting from in utero vitamin D deficiency, age 4 weeks | Plasma Ca and P and urine Ca at 3 and 6 weeks; femur and tibia histomorphometry and urine hydroxyproline at 6 weeks | Addition of lactose to vit-D-deficient diets improved femur and tibia measures relative to other vit-D-deficient groups but improvements did not reach those observed in the control group with adequate vit-D | Schaafsma G, et al. 1988 (Ref. 28) |
| Lactose, lactulose, xylitol, lactobionate, arabinose, raffinose, pyroglutamate, sorbitol, gluconate, and raftilose | 2.5–15% prebiotic by weight of diet | Parallel design, DI; prebiotic treatments each tested over a single night incorporated into the standard diet (AIN-76A); treatments provided in various experimental iterations | Male Fischer 344 rats (n = 8–9 rats per group), age 5–38 weeks | Fractional Ca absorption | All sugars increased fractional Ca absorption relative to control diets lacking prebiotics; additive effects of vit-D and lactulose together were observed; fractional Ca absorption following lactulose consumption and cecectomy remained high | Brommage R, et al. 1993 (Ref. 36) |
| Oligofructose | 0, 25, 50 and 100 g/kg oligofructose, for 16 weeks | Parallel design; 7 groups including sham and OVX control groups; weanling rats were placed on diets with 8 g/kg Ca and 5 g/kg P as run-in until 5 months of age; 6 diets: control (5 g/kg Ca + 0 g/kg oligofructose), 5 g/kg Ca + 25 g/kg oligofructose, 5 g/kg Ca + 50 g/kg oligofructose, 5 g/kg Ca + 100 g/kg oligofructose, 10 g/kg Ca + 0 g/kg oligofructose, 10 g/kg Ca + 50 g/kg oligofructose | Female OVX Fisher 344 rats (n = 96), age 5 months | Apparent Ca absorption; bone microarchitecture | Oligofructose was most effective at influencing Ca absorption and bone microarchitecture when dietary Ca was high; bone loss due to OVX was prevented but different Ca and oligofructose combinations resulted in different microarchitecture changes; compared to controls, 5 g/kg Ca + 100 g/kg oligofructose and 10 g/kg Ca + 50 g/kg oligofructose improved femur Ca content while only 10 g/kg Ca + 50 g/kg oligofructose increased lumbar Ca content; 5 g/kg Ca + 25 g/kg and 100 g/kg oligofructose increased trabecular bone area compared to controls, as did both 10 g/kg Ca diets; at 10 g/kg Ca trabecular number increased with cortical thickness reaching higher levels when 50 g/kg oligofructose was added to the diet | Scholz-Ahrens K, et al. 2002 (Ref. 108) |
| Oligofructose, inulin | 0 or 10% oligofructose or inulin, for 28 days | Parallel design; diet intervention followed a 21 day adaptation period; diets contained 5400 and 520 mg/kg of Ca and Mg, respectively; 5 diets: control, 10% oligofructose (OF), 10% HP-inulin, 10% Synergy1®, or 10% branched-chain inulin | Male Wistar rats (n = 50). age 6 weeks | Ca and Mg absorption; cecal wall and content weight, pH and SCFA content | Ca balance was increased among all ITF treatments relative to controls but no differences were observed between ITF groups; Mg balance was improved with all ITF treatments compared to control; oligofructose and Synergy1® increased Mg absorption more than other ITF treatments; cecal pH was lower and cecal wall and content weight were increased with all ITF treatments; SCFA content was increased among all ITF groups relative to control | Coudray C, et al. 2003 (Ref. 98) |
| Oligofructose + acacia gum, Lactobacillus acidophilus NCC90 | 2.5% oligofructose + acacia gum, for 16 weeks | Parallel design; 5 groups: sham-operated and OVX controls consumed semi-purified diet with 0.7% Ca and 0.5% P (SP diet), remaining 3 groups consumed SP diet with lactobacillus (probiotic), SP diet with 2.5% oligofructose + acacia gum (prebiotic), and SP diet with probiotic and prebiotic (synbiotic); 2 week run-in on SP diet; prebiotic replaced cornstarch in diets | Female OVX Fisher-344 rats (n = 80), age 21 weeks | Apparent absorption and retention of Ca and P; bone biomarkers; bone microarchitecture; intestinal weight and pH; fecal microbial culture analyses | Prebiotic increased Ca absorption, decreased urinary phosphorus, increased cecal content weight, lowered cecal and colon pH and tended to increase calcium balance compared to control; synbiotic reduced pH in small intestine and cecum, and stimulated colonic absorption surface area; synbiotic prevented OVX-induced Ca and P losses in lumbar vertebrae; synbiotic bone-sparing effects were associated with greater fecal bifidobacteria at 6 weeks and greater Bacteroides at 16 weeks; BAP had a tendency to decrease with prebiotic and synbiotic treatments and BAP was negatively correlated with femur P and lumbar Ca and P content | Scholz-Ahrens K, et al. 2016 (Ref. 75) |
| Resistant starch (RS), daidzein (DZ) | 4 diets: control, 0.1% DZ supplement, 12% RS supplement, 0.1% DZ + 12% RS, for 40 days | Parallel design; 6 groups: OVX or sham controls on AIN-93G with corn oil instead of soybean oil; 3 OVX groups consumed supplemented diets; final group was OVX + daily subcutaneous administration of 17 β-estradiol; 4 day run-in on AIN-93G; daidzein/RS replaced sugar/cornstarch in diet | Female ddY mice (n = 36), age 8 weeks | Tibia BMD; amplification of the fecal bacteria 16S DNA and terminal restriction fragment length polymorphism | RS alone did not improve BMD; BMD in the DZ + RS group tended to be higher than in the DZ group; RS feeding resulted in a greater proportion of bifidobacteria species | Tousen Y, et al. 2011 (Ref. 76) |
| Resistant starch (RS), soy isoflavones (IF) | 4 diets: control, 0.05% IF, 9% RS, and 0.05% IF + 9% RS, for 42 days | Parallel design; 5 groups: OVX or sham controls on AIN-93G with corn oil instead of soybean oil; 3 groups consumed supplemented diets; 4 day run-in on AIN-93G; IF/RS replaced sugar/cornstarch in diet; animals pair-fed | Female ddY mice (n = 35), age 8 weeks | Femur BMD and trabecular microarchitecture; cecal content weight and pH; amplification of the fecal bacteria 16S DNA and terminal restriction fragment length polymorphism; bone marrow inflammation | IF + RS increased equol production, prevented the OVX-induced decline in trabecular BMD of the distal femur and improved inflammation in bone marrow; no difference in bone measures between IF + RS and IF diets; diets with RS increased cecal bifidobacteria content | Tousen Y, et al. 2016 (Ref. 77) |
| Resistant Starch (RS60 and 75), Soluble Corn Fiber (SCF), Soluble Fiber Dextrin (SFD), Pullulan, Polydextrose (PDX), Inulin, and Synergy1® (Inulin + FOS) | 4% of prebiotic by weight of diet, for 12 weeks | Parallel design, SI; initially 2 weeks of diets were AIN-93G + 10% prebiotic but due to loose stools in several groups, the % fiber was reduced to 5% after 2 weeks for all treatments and again after another 3 weeks in SCF, SFD, and PDX groups to 4% prebiotic and 1% cellulose; prebiotics replaced cornstarch in diets | Male Sprague Dawley rats (n = 150), age 4 weeks | Ca absorption and mineral (Ca, Zn, Fe, Mg, K and Cu) retention; whole-body BMD, BMC and body composition by DXA; bone density (by water displacement), pQCT and bone-breaking strength of femurs; cecal morphology and fecal SCFA concentrations | Whole-body BMD and BMC were greatest following SCF and SFD consumption; Ca and Mg concentrations in bone and femur contents were improved by RS60, RS75, SFD, PDX, inulin and inulin/FOS; Cu retention was improved by all fibers except inulin; Zn femur content was improved by all fibers but pullulan and SCF; Fe retention was improved by SCF; cecal content weight improved with SFD, SCF, PDX, inulin and Synergy1®; all fibers except RS60 and RS75 increased total SCFA and propionate in the cecum; peak breaking force of femurs was significantly improved by SCF and SFD | Weaver C, et al. 2010 (Ref. 41) |
| sc-FOS | 0 or 100 g/kg of sc-FOS, for 10 days | Parallel design; adequate Ca diet (0.5%) or low Ca diet (0.01%) were administered in conjunction with both sc-FOS treatments | Male Sprague Dawley rats (n = 20), age 4 weeks | Serum Ca concentration; calbindin D9k protein expression; circulating markers of vitamin D and Ca metabolism; small intestine and cecum weight | sc-FOS increased calbindin D9k expression in the large intestine; changing the Ca level of the diet did not have an effect on protein expression; positive correlations were observed between 1,25(OH)2D and calbindin D9k; cecum and colon tissue weight were significantly increased with the addition of sc-FOS; serum Ca was unaffected by sc-FOS | Takasaki M, et al. 2000 (Ref. 102) |
1,25(OH) 2 D 1,25 dihydroxy vitamin D, BMC bone mineral content, BMD bone mineral density, BMI body mass index, Ca calcium, CTx C-telopeptide of type I collagen, Cu copper, DI double-isotope method, DNA deoxyribose nucleic acid, DXA dual-energy X-ray absorptiometry, Fe iron, FOS fructooligosaccharides, GOS galactooligosaccharides, IF isoflavones, ITF inulin-type fructans, Mg magnesium, OVX ovariectomized, P phosphorus, PCR-DGGE polymerase chain reaction-density gradient gel electrophoresis, PDX polydextrose, rRNA ribosomal ribonucleic acid, RS resistant starch, rt-qPCR real-time quantitative polymerase chain reaction, sc-FOS short-chain fructooligosaccharides, SCFA(s) short-chain fatty acid(s), SI single-isotope method, vit-D vitamin D, Zn zinc