A probiotic mixture including galactooligosaccharides decreases fecal β-glucosidase activity but does not affect serum enterolactone concentration in men during a two-week intervention

A high serum concentration of enterolactone, an enterolignan produced by colonic microbiota from precursors in cereals, vegetables, and fruits, is associated with reduced risk of acute coronary events. Probiotics and prebiotics modify colonic metabolism and may affect the serum enterolactone concentration. The effects of a probiotic mixture alone and with galactooligosaccharides (GOS) on serum enterolactone concentration and fecal metabolism were investigated in 18 healthy men. Participants received 3 interventions, each for 2 wk: 1) probiotics [Lactobacillus rhamnosus strains GG (LGG) and LC705, Propionibacterium freudenreichii ssp. shermanii JS, and Bifidobacterium breve Bb99, for a total amount of 2 × 10(10) CFU/d]; 2) probiotics and GOS 3.8 g/d; 3) probiotics, GOS, and rye bread (minimum 120 g/d). Serum enterolactone and fecal dry weight, enzyme activities, pH, SCFA, lactic acid bacteria, bifidobacteria, propionibacteria, and the strains LGG and LC705 were determined. The serum enterolactone concentration (nmol/L) tended to be decreased from baseline [mean (95% CI) 18.6 (10.8-26.4)] by probiotics alone [15.2 (7.8-22.7); P = 0.095], was not significantly affected by probiotics with GOS [21.5 (13.2-29.8)], and was increased by probiotics with GOS and rye bread [24.6 (15.4-33.7); P < 0.05]. Probiotics alone did not affect fecal β-glucosidase activity and bifidobacteria, but probiotics with GOS decreased β-glucosidase activity and increased bifidobacteria compared with baseline (P < 0.05) and with probiotics alone (P < 0.01). In conclusion, this probiotic mixture with or without GOS does not significantly affect serum enterolactone concentration. Because probiotics with GOS decreased fecal β-glucosidase activity but not serum enterolactone, the reduced fecal β-glucosidase, within the range of activities measured, does not seem to limit the formation of enterolactone.     

Supplementation with active hexose correlated compound increases the innate immune response of young mice to primary influenza infection

The emergence of H5N1 avian influenza and the threat of new or adapted viruses in bioterrorism have created an urgent interest in identifying agents to enhance the immune response to primary virus infection. Active hexose correlated compound (AHCC) is a natural mushroom extract reported to increase natural killer (NK) cell activity, survival, and bacterial clearance in young mice. However, the effects of AHCC on the response to viral infections have not been studied. In this study, young C57BL/6 mice were supplemented with 1 g AHCC/(kg body weight x d) for 1 wk prior to and throughout infection with influenza A (H1N1, PR8). Supplementation increased survival, decreased the severity of infection, and shortened recovery time following intranasal infection with flu, as determined by the recovery of body weight and epithelial integrity in the lungs. AHCC increased NK activity in lungs at d 1 (P < 0.05) and d 4 (P < 0.01) and in the spleen at d 2 postinfection (P < 0.01). Supplementation increased the percentage (P < 0.05) and number (P < 0.01) of NK1.1+ cells in the lung and reduced the infiltration of lymphocytes and macrophages compared with controls (P < 0.01). These data suggest that AHCC supplementation boosts NK activity, improves survival, and reduces the severity of influenza infection in young mice. Bolstering innate immunity with dietary bioactives may be one avenue for improving the immune response to primary flu infection.     

The Alleviation of Gut Microbiota-Induced Depression and Colitis in Mice by Anti-Inflammatory Probiotics NK151, NK173, and NK175

Gut microbiota dysbiosis is strongly associated with psychiatric disorders and inflammatory bowel disease (IBD). Herein, we examined whether the fecal microbiota of IBD patients with depression (IBDD) and their gut microbiota culture (iGm) could cause depression and colitis in mice and anti-inflammatory probiotics could mitigate depression in iGm-transplanted or immobilization stress (IS)-exposed mice. Fecal microbiota transplantation (FMT) from IBDD patients, which exhibited Enterobacteriaceae-rich gut microbiota, and its gut microbiota culture (iGm) increased depression-like behaviors in mice. Their treatments heightened the blood lipopolysaccharide (LPS) level and colonic IL-1β and IL-6 expression. However, FMT from healthy volunteers or sulfasalazine treatment alleviated cGm-induced depressive-like behaviors and hippocampal and colonic inflammation in mice. Moreover, oral administration of Lactobacillus plantarum NK151, Bifidobacterium longum NK173, and Bifidobacterium bifidum NK175, which inhibited LPS-induced IL-6 expression in macrophages, alleviated cGm-induced depression-like behaviors, hippocampal NF-κB⁺Iba1⁺ cell numbers and IL-1β and IL-6 expression, blood LPS, IL-6, and creatinine levels, and colonic NF-κB⁺CD11c⁺ number and IL-1β and IL-6 expression in mice. Treatment with NK151, NK173, or NK175 mitigated immobilization stress (IS)-induced depressive-like behaviors, neuroinflammation, and gut inflammation in mice. NK151, NK173, or NK175 also decreased IS-induced blood LPS, IL-6, and creatinine levels. The transplantation of Enterobacteriaceae-rich gut microbiota can cause depression and colitis, as IS exposure, and anti-inflammatory NK151, NK173, and NK175, may alleviate stress-induced fatigue, depression, and colitis by regulating the expression of proinflammatory and anti-inflammatory cytokines through the suppression of gut bacterial LPS.     

Nutrient Intake and Gut Microbial Genera Changes after a 4-Week Placebo Controlled Galacto-Oligosaccharides Intervention in Young Females

Recent interest in the gut-brain-axis has highlighted the potential of prebiotics to impact wellbeing, and to affect behavioral change in humans. In this clinical trial, we examined the impact of four-weeks daily supplementation of galacto-oligosaccharides (GOS) on self-reported nutrient intake and relationships on gut microbiota in a four-week two-armed parallel double-blind placebo controlled GOS supplement trial in young adult females. Food diaries and stool samples were collected prior to and following 28 days of supplement consumption. It was found that four weeks of GOS supplementation influenced macronutrient intake, as evident by reduced carbohydrate and sugars and increased fats intake. Further analysis showed that the reduction in carbohydrates was predicted by increasing abundances of Bifidobacterium in the GOS group in comparison to the placebo group. This suggests that Bifidobacterium increase via GOS supplementation may help improve the gut microbiota composition by altering the desire for specific types of carbohydrates and boosting Bifidobacterium availability when fiber intake is below recommended levels, without compromising appetite for fiber from food.     

Starch with high amylose content and low in vitro digestibility increases intestinal nutrient flow and microbial fermentation and selectively promotes bifidobacteria in pigs

Diets containing different starch types can affect enzymatic digestion of starch and thereby starch availability for microbial fermentation in the gut. However, the role of starch chemistry in nutrient digestion and flow and microbial profile has been poorly explained. Eight ileal-cannulated pigs (29.4 ± 0.9 kg body weight) were fed 4 diets containing 70% purified starch (amylose content, <5, 20, 28, and 63%; reflected by in vitro maximal digestion rate; 1.06, 0.73, 0.38, and 0.22%/min, respectively) in a replicated 4 × 4 Latin square. Ileal and fecal starch output, postileal crude protein yield, fecal total SCFA and total butyrate content, and gene copies of Bifidobacterium spp. in feces were higher (P < 0.05) when pigs consumed the slowly digestible starch diet than the remaining 3 starch diets. The in vitro starch digestion rate had a negative, nonlinear relationship with ileal starch flow (R(2) = 0.98; P < 0.001). Ileal starch flow was positively related to Bifidobacterium spp. (R(2) = 0.27; P < 0.01), Lactobacillus group (R(2) = 0.22; P < 0.01), and total butyrate content (R(2) = 0.46; P < 0.01) but was not related to Enterobacteriaceae (R(2) < 0.00; P = 0.92). In conclusion, starch with high amylose content and low in vitro digestibility increased postileal nutrient flow and microbial fermentation and selectively promoted Bifidobacterium spp. in the distal gut.     

Citation: Tight Junction Protein Expression-Inducing Probiotics Alleviate TNBS-Induced Cognitive Impairment with Colitis in Mice

A leaky gut is closely connected with systemic inflammation and psychiatric disorder. The rectal injection of 2,4,6-trinitrobenzenesulfonic acid (TNBS) induces gut inflammation and cognitive function in mice. Therefore, we selected Bifidobacterium longum NK219, Lactococcus lactis NK209, and Lactobacillus rhamnosus NK210, which induced claudin-1 expression in TNBS- or lipopolysaccharide (LPS)-stimulated Caco-2 cells, from the fecal bacteria collection of humans and investigated their effects on cognitive function and systemic inflammatory immune response in TNBS-treated mice. The intrarectal injection of TNBS increased cognitive impairment-like behaviors in the novel object recognition and Y-maze tests, TNF-α, IL-1β, and IL-17 expression in the hippocampus and colon, and LPS level in the blood and feces, while the expression of hippocampal claudin-5 and colonic claudin-1 decreased. Oral administration of NK209, NK210, and NK219 singly or together decreased TNBS-impaired cognitive behaviors, TNF-α and IL-1β expression, NF-κB⁺Iba1⁺ cell and LPS⁺Iba1⁺ cell numbers in the hippocampus, and LPS level in the blood and feces, whereas BDNF⁺NeuN⁺ cell and claudin-5⁺ cell numbers and IL-10 expression increased. Furthermore, they suppressed TNBS-induced colon shortening and colonic TNF-α and IL-1β expression, while colonic IL-10 expression and mucin protein-2⁺ cell and claudin-1⁺ cell numbers expression increased. Of these, NK219 most strongly alleviated cognitive impairment and colitis. They additively alleviated cognitive impairment with colitis. Based on these findings, NK209, NK210, NK219, and their combinations may alleviate cognitive impairment with systemic inflammation by suppressing the absorption of gut bacterial products including LPS into the blood through the suppression of gut bacterial LPS production and alleviation of a leaky gut by increasing gut tight junction proteins and mucin-2 expression.     

Lactobacillus rhamnosus GG and Bifidobacterium animalis MB5 induce intestinal but not systemic antigen-specific hyporesponsiveness in ovalbumin-immunized rats

Probiotics may modulate the host immune response by mechanisms not yet fully understood. We evaluated the modulation of intestinal and systemic antigen-specific immune response by Lactobacillus rhamnosus GG (LGG) or Bifidobacterium animalis MB5 in tolerized and immunized rats. Three groups of rats received orally LGG, B. animalis, or PBS (control) for 28 d. Each group was divided into two subgroups of tolerized or immunized rats receiving orally ovalbumin (OVA; 7 mg) or PBS on d 7, 9, and 11. All rats were immunized with OVA (300 μg) on d 14 and 21. In tolerized rats, the OVA-induced proliferative response of mesenteric lymph nodes (MLN) and spleen cells did not differ from control, indicating that the two probiotics maintained the tolerance. LGG and B. animalis in immunized rats reduced the OVA-induced proliferative response in MLN (P < 0.01) but not in spleen, whereas the proliferative response to anti-CD3 and concanavalin A of MLN and spleen cells as well as the delayed-type hypersensitivity reaction were not affected by probiotic treatment, indicating OVA-specific hyporesponsiveness restricted to intestinal immunity. This hyporesponsiveness was associated with CD4+CD25+Foxp3+ T cell expansion (P < 0.01) and increased IL-10 and TGFβ after LGG (P < 0.05), and increased apoptosis after B. animalis (P < 0.001) in MLN. In conclusion, we report a novel activity of LGG and B. animalis in inducing OVA-specific hyporesponsiveness in MLN of OVA-immunized rats that can be useful for a therapeutic strategy to prevent undesirable reactions to immunogenic antigens in the gut.     

Docosahexaenoic acid-enriched fish oil consumption modulates immunoglobulin responses to and clearance of enteric reovirus infection in mice

We hypothesized that consumption of the (n-3) PUFA, docosahexaenoic acid (DHA), modulates the mucosal immune response to enteric infection with respiratory enteric orphan virus (reovirus), a model intestinal pathogen. Mice were fed either AIN-93G control diet, containing 10 g/kg corn oil and 60 g/kg high oleic acid safflower oil, or AIN-93G, containing 10 g/kg corn oil and 60 g/kg DHA-enriched fish oil, for 4 wk and then orally gavaged with reovirus strain Type 1 Lang, (T1/L). Reovirus-specific IgA antibody was first detectable in the feces of mice fed a control diet at 6 d postinfection (PI) and was further elevated at 8 and 10 d PI. IgA responses in DHA-fed mice were similar at 6 and 8 d PI but greater at 10 d PI (P < 0.05). Both reovirus-specific serum IgA and IgG(2a) were comparably induced in mice fed control or DHA diets. Reovirus-specific IgA and IgG(2a) secretion by ex vivo Peyer's patch, lamina propria, and spleen cultures derived from control and DHA groups were comparable. Although both groups carried similar numbers of reovirus plaque forming units per intestine, DHA-fed mice shed nearly 10 times more viral RNA in feces than control mice at 2, 4, and 6 d PI (P < 0.05). However, viral RNA was not detectable in either group at 8 and 10 d. Taken together, these data suggest that DHA consumption did not markedly alter mucosal or systemic Ig responses to reovirus but delayed clearance of the virus from the intestinal tract.     

Weight loss, but not fish oil consumption, improves fasting and postprandial serum lipids, markers of endothelial function, and inflammatory signatures in moderately obese men

Overweight persons are at risk for cardiovascular diseases, which may relate to a disturbed endothelial function and pro-inflammatory serum profiles. Indeed, weight loss lowers cardiovascular disease risk, but weight maintenance is difficult. Therefore, dietary supplements such as fish oil, which improve endothelial function, are useful. In this study, we evaluated effects of fish oil and moderate weight loss in the same population. For this, 11 normolipidemic healthy, moderately obese men (BMI 30-35 kg/m2) received in random order 1.1 g/d eicosapentanoic acid (EPA) + docosahexanoic acid (DHA) or oleic acid (control) for 6 wk. In the 3rd period, 8 of the 11 subjects consumed low-energy diets (2 MJ/d) for 4 wk followed by 4 wk weight stabilization. Their body weight was reduced by 9.4 +/- 2.0 kg (P < 0.05). On the final day of all 3 periods, a postprandial test was conducted. Weight loss lowered fasting and postprandial plasma triacylglycerol (TG) responses (P < 0.001), whereas fish oil reduced only postprandial TG (P = 0.006). Fish oil did not affect soluble intercellular adhesion molecule (s-ICAM), whereas weight loss reduced fasting (P = 0.009) and postprandial s-ICAM responses (P < 0.001). Fasting s-ICAM and TG correlated (r = 0.68; P = 0.029), as did changes in fasting s-ICAM and TG during weight loss (r = 0.80; P = 0.029) and fish oil treatment (r = 0.76; P = 0.009). Fasting (P = 0.027) and postprandial (P < 0.001) serum C-reactive protein were lowered by weight loss. The postprandial monocyte chemoattractant protein-1 response was lowered by fish oil and after weight loss (P < 0.001). This indicates that 1.1 g/d EPA+DHA supplied for 6 wk, in contrast to approximately 10 kg weight loss, does not improve markers of endothelial function and inflammation.     

A novel galactooligosaccharide mixture increases the bifidobacterial population numbers in a continuous in vitro fermentation system and in the proximal colonic contents of pigs in vivo

Prebiotics are nondigestible food ingredients that encourage proliferation of selected groups of the colonic microflora, thereby altering the composition toward a more beneficial community. In the present study, the prebiotic potential of a novel galactooligosaccharide (GOS) mixture, produced by the activity of galactosyltransferases from Bifidobacterium bifidum 41171 on lactose, was assessed in vitro and in a parallel continuous randomized pig trial. In situ fluorescent hybridization with 16S rRNA-targeted probes was used to investigate changes in total bacteria, bifidobacteria, lactobacilli, bacteroides, and Clostridium histolyticum group in response to supplementing the novel GOS mixture. In a 3-stage continuous culture system, the bifidobacterial numbers for the first 2 vessels, which represented the proximal and traverse colon, increased (P < 0.05) after the addition of the oligosaccharide mixture. In addition, the oligosaccharide mixture strongly inhibited the attachment of enterohepatic Escherichia coli (P < 0.01) and Salmonella enterica serotype Typhimurium (P < 0.01) to HT29 cells. Addition of the novel mixture at 4% (wt:wt) to a commercial diet increased the density of bifidobacteria (P < 0.001) and the acetate concentration (P < 0.001), and decreased the pH (P < 0.001) compared with the control diet and the control diet supplemented with inulin, suggesting a great prebiotic potential for the novel oligosaccharide mixture.     

Effects of galactooligosaccharide and long-chain fructooligosaccharide supplementation during pregnancy on maternal and neonatal microbiota and immunity--a randomized, double-blind, placebo-controlled study

BACKGROUND: Galactooligosaccharides (GOS) and long-chain fructooligosaccharides (lcFOS) proliferate bifidobacteria in infant gut microbiota. However, it is not known how GOS and FOS influence the microbiota of pregnant women and whether a potential prebiotic effect is transferred to the offspring. OBJECTIVES: We aimed to test how supplementation with GOS and lcFOS (GOS/lcFOS) in the last trimester of pregnancy affects maternal and neonatal gut microbiota. Variables of fetal immunity were assessed as a secondary outcome. DESIGN: In a randomized, double-blind, placebo-controlled pilot study, 48 pregnant women were supplemented 3 times/d with 3 g GOS/lcFOS (at a ratio of 9:1) or maltodextrin (placebo) from week 25 of gestation until delivery. Percentages of bifidobacteria and lactobacilli within total bacterial counts were detected by fluorescent in situ hybridization and quantitative polymerase chain reaction in maternal and neonatal (days 5, 20, and approximately 182) stool samples. Variables of fetal immunity were assessed in cord blood by using flow cytometry and cytokine multiplex-array analysis. RESULTS: The proportions of bifidobacteria in the maternal gut were significantly higher in the supplemented group than in the placebo group (21.0% and 12.4%, respectively; P = 0.026); the proportion of lactobacilli did not differ between the groups. In neonates, bifidobacteria and lactobacilli percentages, diversity and similarity indexes, and fetal immune parameters did not differ significantly between the 2 groups. Mother-neonate similarity indexes of bifidobacteria decreased over time. CONCLUSIONS: GOS/lcFOS supplementation has a bifidogenic effect on maternal gut microbiota that is not transferred to neonates. The increased maternal bifidobacteria did not affect fetal immunity as measured by a comprehensive examination of cord blood immunity variables.     

Oral glutamine prevents DMBA-induced mammary carcinogenesis via upregulation of glutathione production

OBJECTIVE: Glutamine is suggested to participate in glutathione synthesis. Furthermore, there is a positive relation between glutathione level and natural killer (NK) cell activity. Previously we demonstrated that supplemental glutamine inhibited tumor growth in an implantable tumor model and 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral squamous cell carcinoma model; these reductions were associated with enhancing NK cell cytotoxicity, blood glutathione levels, and/or gut glutathione release. Therefore, we hypothesized that oral glutamine might suppress DMBA-induced mammary carcinogenesis by upregulation of glutathione production and/or augmentation of NK cell activity. METHODS: Rats were randomized to six groups: DMBA + glutamine, DMBA + Freamine, DMBA + water, oil + glutamine, oil + Freamine, or oil + water. At age 50 d, rats were gavaged with DMBA or sesame oil. Rats also received glutamine, Freamine, or water by gavage from 1 wk before DMBA administration until sacrifice at 1, 2, 4, or 11 wk after DMBA. Tumor appearance, blood, gut mucosa and breast glutamine and/or glutathione concentrations, and NK cell cytotoxicity were measured. The gut extractions, defined as the difference of concentrations across the gut, were calculated. RESULTS: Oral glutamine reduced the tumorigenesis of DMBA by 50% in this model. DMBA altered the difference of glutathione concentrations across the gut; however, oral glutamine maintained the normal gut glutathione release. NK cell activities were lower in DMBA groups at early (week 1) and late (week 11) time points, but oral glutamine recovered the NK cell activity only at week 11. In addition, blood, gut, and breast glutathione concentrations were enhanced by glutamine supplementation. CONCLUSION: These results indicate that one of the mechanisms of dietary glutamine anticancer action is through upregulating gut glutathione metabolism.     

Photoprotective effects of galacto-oligosaccharide and/or Bifidobacterium longum supplementation against skin damage induced by ultraviolet irradiation in hairless mice

Abstract

This study aimed at examining whether oral administration of galacto-oligosaccharide (GOS) and Bifidobacterium longum, individually or in combination, could exert photoprotective effects on the skin of hairless mice. GOS and/or Bifidobacterium were administered orally to hairless mice for 12 weeks. Mice were irradiated with UV light daily for four consecutive days. GOS administration increased the water-holding capacity of the skin and prevented transepidermal water loss compared with the control. A reduction in the erythema formation of 16.8% was also observed in the GOS-treated group compared with the control, and CD44 gene expression was significantly increased. Oral administration of GOS or Bifidobacterium significantly increased TIMP-1 and Col1 mRNA expression compared with the control. Our findings support that prebiotics, including GOS, are beneficial not only to the intestine, but also to the skin, and present the possibility of new nutritional strategies for the prevention of UV-induced skin damage.     

Assessment of the safety, tolerance, and protective effect against diarrhea of infant formulas containing mixtures of probiotics or probiotics and prebiotics in a randomized controlled trial

BACKGROUND: Probiotics and prebiotics are considered to be beneficial to the gastrointestinal health of infants. OBJECTIVE: The objective was to evaluate infant formulas containing probiotics and synbiotics (combinations of probiotics and prebiotics) for safety and tolerance. DESIGN: In a prospective, controlled, double-blind, randomized trial, healthy full-term infants were exclusively fed a control formula or study formulas containing Bifidobacterium longum BL999 (BL999) + Lactobacillus rhamnosus LPR (LPR), BL999 + LPR + 4 g/L of 90% galactooligosaccharide/10% short-chain fructooligosaccharide (GOS/SCFOS), or BL999 + Lactobacillus paracasei ST11 (ST11) + 4 g/L GOS/SCFOS from < or = 2 to 16 wk of age (treatment period). Safety and tolerance were assessed based on weight gain during the treatment period (primary outcome) as well as recumbent length, head circumference, digestive tolerance, and adverse events (secondary outcomes), which were evaluated at 2, 4, 8, 12, 16, and 52 wk of age. RESULTS: Two hundred eighty-four infants were enrolled. During the treatment period, difference in mean weight gain between control and study formula groups in both the intention-to-treat and per-protocol populations were within the predefined equivalence boundaries of +/-3.9 g/d, indicating equivalent weight gain. Secondary outcomes did not show significant differences between groups during the treatment period. CONCLUSION: Infants fed formulas containing probiotics or synbiotics show a similar rate in weight gain compared with those fed a control formula and tolerate these formulas well.     

Folate status of elderly women following moderate folate depletion responds only to a higher folate intake

Dietary Reference Intakes (DRI) for folate for elderly women have been based primarily on data extrapolated from studies in younger women. This study was conducted to provide the first age-specific data in elderly women (60-85 y) from a controlled metabolic study on which to base folate intake recommendations. Subjects (n = 33) consumed a moderately folate-deplete (118 microg/d) diet for 7 wk, followed by repletion diets providing either 200 or 415 microg folate/d as diet plus folic acid (FA) or a combination of FA and orange juice (OJ) for 7 wk (n = 30). Comparisons among and within groups were made for serum folate (SF), RBC folate and plasma total homocysteine (tHcy) concentrations. SF concentrations decreased significantly (P < 0.001) during depletion (65 +/- 15%). Postrepletion, the adjusted SF concentration for subjects consuming 415 microg folate/d was significantly greater (P = 0.003) than for subjects consuming 200 microg folate/d. RBC folate concentrations decreased (P < 0.001) during depletion (21 +/- 10%) and further (P < 0.001) during repletion (5 +/- 14%). During depletion, plasma tHcy concentrations increased significantly (P < 0.001) and an inverse relationship between SF and plasma tHcy concentrations was observed in 94% of subjects (P < 0.001). Reversal of this inverse relationship was significant only for subjects consuming 415 microg folate/d (P < 0.001). Postrepletion, subjects consuming 200 microg folate/d had a significantly higher (P = 0.009) adjusted plasma tHcy concentration than subjects consuming 415 microg folate/d. These data in elderly women indicate that 415 microg/d folate, provided as a combination of diet, FA and OJ, or diet and FA, normalizes folate status more effectively than does 200 microg/d, thus providing age-specific data for future folate intake recommendations.     

Dietary supplementation with white button mushroom enhances natural killer cell activity in C57BL/6 mice

Mushrooms are reported to possess antitumor, antiviral, and antibacterial properties. These effects of mushrooms are suggested to be due to their ability to modulate immune cell functions. However, a majority of these studies evaluated the effect of administering extracts of exotic mushrooms through parental routes, whereas little is known about the immunological effect of a dietary intake of white button mushrooms, which represent 90% of mushrooms consumed in the U.S. In this study, we fed C57BL/6 mice a diet containing 0, 2, or 10% (wt/wt) white button mushroom powder for 10 wk and examined indices of innate and cell-mediated immunity. Mushroom supplementation enhanced natural killer (NK) cell activity, and IFNgamma and tumor necrosis factor-alpha (TNFalpha) production, but only tended to increase IL-2 (P = 0.09) and did not affect IL-10 production by splenocytes. There were significant correlations between NK activity and production of IFNgamma (r = 0.615, P < 0.001) and TNFalpha (r = 0.423, P = 0.032) in splenocytes. Mushroom supplementation did not affect macrophage production of IL-6, TNFalpha, prostaglandin E(2), nitric oxide, and H(2)O(2), nor did it alter the percentage of total T cells, helper T cells (CD4(+)), cytotoxic or suppressive T cells (CD8(+)), regulatory T cells (CD4(+)/CD25(+)), total B cells, macrophages, and NK cells in spleens. These results suggest that increased intake of white button mushrooms may promote innate immunity against tumors and viruses through the enhancement of a key component, NK activity. This effect might be mediated through increased IFNgamma and TNFalpha production.     

Synergy between Lactobacillus paracasei and its bacterial products to counteract stress-induced gut permeability and sensitivity increase in rats

Stressful events result in the alteration of gut permeability and sensitivity. Lactobacillus paracasei NCC2461 (Lpa) therapy prevents antibiotic-induced visceral hyperalgesia in mice. This study aimed at evaluating the influence of 3 probiotic strains: Bifidobacterium lactis NCC362, Lactobacillus johnsonii NCC533, and Lpa on stress-mediated alterations of colorectal hyperalgesia, on gut paracellular permeability and whether bacteria and/or bacterial products present in the spent culture medium (SCM) were involved in the antinociceptive properties of the effective strain. Rat pups were separated from their mothers 3 h/d during postnatal d 2-14. At wk 13, gut paracellular permeability was determined as a percentage of urinary excreted (51)Cr-EDTA and visceral sensitivity to colorectal distension (CRD), assessed by abdominal muscle electromyography. Visceral sensitivity was also analyzed in adults rats subjected to partial restraint stress (PRS, 2 h restriction of body movements). Rats received either the probiotics resuspended in SCM or fresh growth medium as control for 2 wk. Maternal deprivation significantly increased colonic sensitivity in response to CRD and enhanced gut paracellular permeability compared with control rats. Only Lpa treatment significantly improved stress-induced visceral pain and restored normal gut permeability. Similarly, among the 3 probiotics tested, only Lpa prevented PRS-mediated visceral hyperalgesia. Both bacteria and bacterial products present in Lpa SCM were required for the antinociceptive properties against PRS. This study illustrates strain-specific effects and suggests a synergistic interplay between L. paracasei bacteria and bacterial products generated during fermentation and growth that confers the ability to suppress PRS-induced hypersensitivity in rats.     

Decreasing linoleic acid with constant alpha-linolenic acid in dietary fats increases (n-3) eicosapentaenoic acid in plasma phospholipids in healthy men

High linoleic acid (LA) intakes have been suggested to reduce alpha-linolenic acid [ALA, 18:3(n-3)] metabolism to eicosapentaenoic acid [EPA, 20:5(n-3)] and docosahexaenoic acid [DHA, 22:6(n-3)], and favor high arachidonic acid [ARA, 20:4(n-6)]. We used a randomized cross-over study with men (n = 22) to compare the effect of replacing vegetable oils high in LA with oils low in LA in foods, while maintaining constant ALA, for 4 wk each, on plasma (n-3) fatty acids. Nonvegetable sources of fat, except fish and seafoods, were unrestricted. We determined plasma phospholipid fatty acids at wk 0, 2, 4, 6, and 8, and triglycerides, cholesterol, serum CRP, and IL-6, and platelet aggregation at wk 0, 4, and 8. LA and ALA intakes were 3.8 +/- 0.12% and 1.0 +/- 0.05%, and 10.5 +/- 0.53% and 1.1 +/- 0.06% energy with LA:ALA ratios of 4:0 and 10:1 during the low and high LA diets, respectively. The plasma phospholipid LA was higher and EPA was lower during the high than during the low LA diet period (P < 0.001), but DHA declined over the 8-wk period (r = -0.425, P < 0.001). The plasma phospholipid ARA:EPA ratios were (mean +/- SEM) 20.7 +/- 1.52 and 12.9 +/- 1.01 after 4 wk consuming the high or low LA diets, respectively (P < 0.001); LA was inversely associated with EPA (r = -0.729, P < 0.001) but positively associated with ARA:EPA (r = 0.432, P < 0.001). LA intake did not influence ALA, ARA, DPA, DHA, or total, LDL or HDL cholesterol, CRP or IL-6, or platelet aggregation. In conclusion, high LA intakes decrease plasma phospholipid EPA and increase the ARA:EPA ratio, but do not favor higher ARA.     

Ascorbic acid supplementation and regular consumption of fresh orange juice increase the ascorbic acid content of human milk: studies in European and African lactating women

BACKGROUND: Little is known about the influence of an increased intake of ascorbic acid (AA) on human milk AA output. OBJECTIVE: We aimed to compare human milk AA content in European and African women and to evaluate the influence of increased AA intake on human milk AA output. DESIGN: Apparently healthy lactating women were recruited. AA was analyzed by titration with 2,6-dichlorophenol-indophenol. RESULTS: Mean human milk AA was approximately 50% lower (P < 0.001) in the African women (31 mg/kg; n = 171) than in the European women (63 mg/kg; n = 142). AA supplementation (1000 mg/d for 10 d) increased mean human milk AA from 19 to 60 mg/kg (P < 0.001) and from 60 to 70 mg/kg (P = 0.03) in 18 African and 10 European women, respectively. In 11 African women, mean human milk AA increased from 17 to 36 mg/kg (P < 0.001) after intake of 100 mg AA/d for 10 d. In African women, intake of 1 serving of orange juice per week had no significant effect, whereas 3 or 5 servings/wk ( approximately 100 mg AA/serving) for 6 wk increased mean human milk AA from 16 to 32 mg/kg (n = 13) and from 21 to 46 mg/kg (n = 13), respectively (P < 0.001). CONCLUSIONS: Human milk AA can be doubled or tripled by increased intake of AA in women with low human milk AA content at baseline. The response to a relatively high dose of AA was modest in European women in contrast with the 3-fold increase in mean human milk AA content in African women. These data indicate that human milk AA content is regulated.     

Dietary nucleotides and fecal microbiota in formula-fed infants: a randomized controlled trial

BACKGROUND: Dietary nucleotides are nonprotein nitrogenous compounds that are thought to be important for growth, repair, and differentiation of the gastrointestinal tract. A higher nucleotide intake may also have favorable effects on the fecal microbial composition and incidence of diarrhea in infancy. However, few studies have tested this hypothesis with an experimental study design. OBJECTIVE: We tested the hypothesis that nucleotide supplementation of infant formula has beneficial effects on fecal bacteriology. DESIGN: Oligonucleotide probes were used to measure bacterial genus-specific 16S ribosomal RNA in stools of a subset of infants (mean age: 20.4 wk) who were randomly assigned to nucleotide-supplemented (31 mg/L; n = 35) or control formula (n = 37) from birth until age 20 wk or were breastfed (reference group; n = 44). The microbial pattern was assessed as the ratio of Bacteroides-Porphyromonas-Prevotella group (BPP) to Bifidobacterium species. RESULTS: The ratio of BPP to Bifidobacterium spp. rRNA in infants randomly assigned to the nucleotide-supplemented formula was lower than in infants receiving the control formula (mean difference: -118%; 95% CI: -203%, -34%; P = 0.007), but it did not differ in infants who were breastfed. The difference between randomized formula-fed groups was independent of potential confounding factors (P = 0.003). CONCLUSIONS: Our data support the hypothesis that nucleotide supplementation improves the composition of the gut microbiota in formula-fed infants. Because this effect could contribute to previously described benefits of nucleotide supplementation for gastrointestinal tract and immune function, these findings have important implications for optimizing the diet of formula-fed infants.