Christopher R. Villa

Health Effects of Mixed Fruit and Vegetable Concentrates: A Systematic Review of the Clinical Interventions

Diets rich in fruits and vegetables (FV) have been associated with a reduced risk of chronic disease, including cardiovascular disease. Unfortunately, public health campaigns to increase FV intake have had limited success. A number of mixed concentrated FV products have been studied, which may help certain individuals improve nutrient status. However, the possible health benefits of FV supplements have not been systematically reviewed. We, therefore, undertook a systematic search of MEDLINE and EMBASE to identify clinical interventions that examined the effect of commercially available concentrated mixed FV supplements on cardiovascular disease risk factors. Twenty-two reports, which used commercially available products, were identified. None of the studies reported any serious adverse effects. Overall, daily consumption of FV supplements significantly increased serum concentrations of the major antioxidant provitamins and vitamins found in plant foods (β-carotene, vitamins C and E) and folate. Functional changes, such as reduced serum homocysteine and markers of protein, lipid, and DNA oxidation, were also reported; in addition, the health advantages on markers of inflammation, immunity, and endothelial function are promising. Limitations of the available studies were related to the diversity of studies conducted with respect to design and study population and the variability in the measured outcomes and assays utilized. While mixed FV supplements may serve as an efficacious complement for individuals who have difficulty achieving their daily FV intake requirement, further research on additional retail preparations is warranted. Key teaching points: •  Mixed fruit and vegetable supplements produced from plant foods may serve as an efficacious complement to the habitual diet in individuals who have suboptimal intake or variety of nutrient-dense fruits and vegetables.•  Current research indicates that fruit and vegetable concentrates significantly increase serum levels of antioxidant provitamins and vitamins (β-carotene, vitamins C and E) and folate and reduce homocysteine and markers of oxidative stress.•  Mechanistic studies and larger, randomized, placebo-controlled double-blind trials in both healthy and high-risk populations are necessary to better understand the health effects of these supplements.

Impact of Bifidobacterium bifidum MIMBb75 on mouse intestinal microorganisms

Bifidobacterium bifidum MIMBb75 is a recently identified probiotic. However, its distribution along the intestine and impact on resident microbiota is unknown. Herein, we established a quantitative real-time polymerase chain reaction assay targeting the B. bifidum-specific BopA region for the quantification of B. bifidum in feces and used this assay to investigate transit of B. bifidum MIMBb75 through the murine intestine. We also analyzed the consequential impact on resident microbial cohorts. C57BL/6J mice were daily gavaged with 0.2 mL of either sterile PBS or PBS containing 10(8) colony-forming units of B. bifidum MIMBb75 for 2 weeks, after which intestinal contents and fecal samples were analyzed for microbial compositional changes. Bifidobacterium bifidum MIMBb75 was able to transiently colonize the murine intestine, with the predominant niche being the ceco-proximal colonic region. Region-specific effects on host microbiota were observed including decreased levels of Clostridium coccoides in the cecum, increased levels of bifidobacteria in the proximal and distal colon, total bacteria and Clostridium leptum in the proximal colon, and of C. coccoides in the feces. These findings suggest that probiotic properties of B. bifidum MIMBb75 may partially depend on its ability to at least transiently colonize the intestine and impact on the resident microbial communities at various intestinal loci.

Gut Microbiota-bone Axis.

ABSTRACT The gut microbiota (GM) is an important regulator of body homeostasis, including intestinal and extra-intestinal effects. This review focuses on the GM-bone axis, which we define as the effect of the gut-associated microbial community or the molecules they synthesize, on bone health. While research in this field is limited, findings from preclinical studies support that gut microbes positively impact bone mineral density and strength parameters. Moreover, administration of beneficial bacteria (probiotics) in preclinical models has demonstrated higher bone mineralization and greater bone strength. The preferential bacterial genus that has shown these beneficial effects in bone is Lactobacillus and thus lactobacilli are among the best candidates for future clinical intervention trials. However, their effectiveness is dependent on stage of development, as early life constitutes an important time for impacting bone health, perhaps via modulation of the GM. In addition, sex-specific difference also impacts the efficacy of the probiotics. Although auspicious, many questions regarding the GM-bone axis require consideration of potential mechanisms; sex-specific efficacy; effective dose of probiotics; and timing and duration of treatment.

Maternal vitamin D beneficially programs metabolic, gut and bone health of mouse male offspring in an obesogenic environment

Background/Objectives:Vitamin D is an anti-inflammatory nutrient and a determinant of bone health. Some prospective studies suggest that maternal vitamin D status is positively associated with offspring bone mass. We found that serum concentrations of lipopolysaccharide (LPS), an inflammatory molecule related to adiposity, insulin resistance and bone resorption, is lower in healthy mouse offspring exposed to high dietary vitamin D during pregnancy and lactation. LPS reaches the circulation via the gut. This study investigated whether maternal vitamin D programs metabolic, gut and bone health of male offspring in an obesogenic environment.Methods:C57BL/6J dams received an AIN-93G diet with high (H) or low (L) vitamin D during pregnancy and lactation. At weaning, offspring remained on their dam’s vitamin D level (LL or HH) or were switched (LH or HL) and fed a high fat (44.2%) and sucrose (19.8%) diet. Glucose response, adiposity, systemic inflammation (LPS, cytokines), intestinal permeability and mass, strength and microarchitecture of trabecular and cortical bone were assessed in 7-month-old male offsprings.Results:Higher maternal dietary vitamin D resulted in lower intestinal permeability (fecal albumin, P=0.010) and benefited trabecular but not cortical bone structure at the distal femur (higher trabecular number, P=0.022; less trabecular separation, P=0.015) and lumbar vertebra 2 (bone volume/total volume%, P=0.049). Higher maternal and offspring vitamin D resulted in lower fasting glucose (HH versus LL, P=0.039) and serum LPS concentrations (dam diet, P=0.011; pup diet, P=0.002). Higher offspring vitamin D resulted in lower epididymal fat pad relative weight (P=0.006). The serum concentrations of IL-6 and TNF-α did not differ among groups.Conclusions:Maternal dietary vitamin D beneficially programs intestinal permeability and systemic LPS concentration, which is accompanied by stronger trabecular bone in an obesogenic environment. Thus, the gut may mediate vitamin D effects. Moreover, optimizing vitamin D in early life may be critical for later health.

Maternal Dietary Vitamin D Does Not Program Systemic Inflammation and Bone Health in Adult Female Mice Fed an Obesogenic Diet

Obesity is associated with systemic inflammation and impaired bone health. Vitamin D regulates bone metabolism, and has anti-inflammatory properties and epigenetic effects. We showed that exposure to high dietary vitamin D during pregnancy and lactation beneficially programs serum concentration of lipopolysaccharide (LPS) and bone structure in male offspring fed an obesogenic diet. Here we assessed if this effect is also apparent in females. C57BL/6J dams were fed AIN93G diet with high (5000 IU/kg diet) or low (25 IU/kg diet) vitamin D during pregnancy and lactation. Post-weaning, female offspring remained on their respective vitamin D level or were switched and fed a high fat and sucrose diet (44.2% fat, 19.8% sucrose) until age seven months when glucose response, adiposity, serum LPS, and bone mineral, trabecular and cortical structure, and biomechanical strength properties of femur and vertebra were assessed. There was no evidence for a programming effect of vitamin D for any outcomes. However, females exposed to a high vitamin D diet post-weaning had higher bone mineral content (p = 0.037) and density (p = 0.015) of lumbar vertebra. This post-weaning benefit suggests that in females, bone mineral accrual but not bone structure is compromised with low vitamin D status in utero until weaning in an obesogenic context.

Prevalence of positive coeliac disease serology and HLA risk genotypes in a multiethnic population of adults in Canada: a cross-sectional study

Objectives Coeliac disease (CD) is a complex autoimmune disorder with known genetic risk factors. Approximately 1% of individuals of European ancestry have CD, but the prevalence among different ethnicities living in Canada remains unknown. The objective of the present study was to determine the prevalence of positive CD serology in a population of Canadian adults living in Toronto, and to determine whether the prevalence of CD seropositivity and predisposing human leucocyte antigen (HLA)-DQ2/DQ8 risk genotypes differ between major ethnocultural groups. Design Cross-sectional screening study of participants from the Toronto Nutrigenomics and Health and the Toronto Healthy Diet studies. Setting University campus and households across Toronto, Canada. Participants: free-living Adults (n=2832) of diverse ethnocultural backgrounds. Main outcome measures Prevalence of positive CD serology was determined by screening for antitissue transglutaminase antibodies in individuals with predisposing HLA-DQ2/DQ8 genotypes. HLA genotypes were determined using six single nucleotide polymorphisms in the HLA gene region. Results Of the 2832 individuals screened, a total of 25 (0.88%; 95% CI 0.57% to 1.30%) were determined to have positive CD serology. The majority of seropositive CD cases were undiagnosed (87%). Prevalence was highest among Caucasians (1.48%; 95% CI 0.93% to 2.23%), and similar in those of ‘Other’ (0.74%; 95% CI 0.09% to 2.63%) or ‘Unknown’ (0.43; 95% CI 0.01% to 2.36%) ethnicity. No cases of positive CD serology were identified among East Asian or South Asian individuals. East Asians had a lower prevalence of HLA risk genotypes than Caucasians and South Asians (p<0.005). Conclusions The prevalence of positive CD serology among Canadian adults living in Toronto is likely ~1%, with 87% of cases being undiagnosed. These findings suggest the need for better screening in high genetic risk groups. Trial registration number NCT00516620; Post-results.

Colonic Bacteroides are positively associated with trabecular bone structure and programmed by maternal vitamin D in male but not female offspring in an obesogenic environment

Background/Objectives:The gut microbiota is determined early in life, possibly including pregnancy. Pioneering data suggest vitamin D, a nutrient important for bone health, affects this microbiota. We found that high maternal vitamin D lowered circulating lipopolysaccharide (LPS), improved intestinal barrier and bone health in male but not female offspring in an obesogenic environment. This study determined if high maternal dietary vitamin D programs Bacteroides and Prevotella and whether this associates with bone mineral content, density and structure of male and female adult offspring fed an obesogenic diet.Methods:C57BL/6J females received an AIN93G diet with high or low vitamin D from before mating until weaning. Post-weaning, male and female offspring remained on their respective vitamin D level or were switched and fed a high fat and sucrose diet until killing (age 7 months). Bacteroides and Prevotella were quantified in dams’ feces and offspring colonic contents. LPS concentrations, bone mineral density and content, strength and structure data were integrated from our previous studies in the same mice. Spearman correlations were completed between Bacteroides and LPS, and bone outcomes.Results:There was a maternal vitamin D effect on colonic Bacteroides but not Prevotella (dam diet: <0.001 and 0.735) in adult male offspring, independent of dams fecal Bacteroides before birth (P=0.998). In males, but not females, Bacteroides correlated with LPS (r=−0.488, P=0.018), trabecular femur peak load (r=0.362, P=0.033), vertebral trabecular separation (r=−0.605, P=0.006), trabecular number (r=0.614, P=0.005) and bone volume fraction (r=0.549, P=0.015).Conclusions:Dietary vitamin D programs Bacteroides in male adult offspring only, which correlated negatively with systemic inflammation and positively with bone strength and structure. This may have implications on maternal diet and nutritional guidelines targeting sexes in a different manner.