Effects of parental omega-3 fatty acid intake on offspring microbiome and immunity.

The "Western diet" is characterized by increased intake of saturated and omega-6 (n-6) fatty acids with a relative reduction in omega-3 (n-3) consumption. These fatty acids can directly and indirectly modulate the gut microbiome, resulting in altered host immunity. Omega-3 fatty acids can also directly modulate immunity through alterations in the phospholipid membranes of immune cells, inhibition of n-6 induced inflammation, down-regulation of inflammatory transcription factors, and by serving as pre-cursors to anti-inflammatory lipid mediators such as resolvins and protectins. We have previously shown that consumption by breeder mice of diets high in saturated and n-6 fatty acids have inflammatory and immune-modulating effects on offspring that are at least partially driven by vertical transmission of altered gut microbiota. To determine if parental diets high in n-3 fatty acids could also affect offspring microbiome and immunity, we fed breeding mice an n-3-rich diet with 40% calories from fat and measured immune outcomes in their offspring. We found offspring from mice fed diets high in n-3 had altered gut microbiomes and modestly enhanced anti-inflammatory IL-10 from both colonic and splenic tissue. Omega-3 pups were protected during peanut oral allergy challenge with small but measurable alterations in peanut-related serologies. However, n-3 pups displayed a tendency toward worsened responses during E. coli sepsis and had significantly worse outcomes during Staphylococcus aureus skin infection. Our results indicate excess parental n-3 fatty acid intake alters microbiome and immune response in offspring

Dermatologic Consequences of Substandard, Spurious, Falsely Labeled, Falsified, and Counterfeit Medications

This article explores dermatologic consequences of substandard, spurious, falsely labeled, falsified, and counterfeit (SSFFC) pharmaceutical products. Many of these SSFFC products are neither safe nor effective, and are more likely to cause adverse events than the proper preparations. These products also affect the health of populations by generating drug-resistant pathogens and failing to control the spread of disease. This article reviews classification systems for fraudulent medications, provides a general overview of medical and public health problems associated with substandard medications, provides examples of dermatologic consequences of each category, and presents recommended steps to take when clinicians encounter suspected SSFFC products

High omega-3 intake altered colonic inflammation and gut microbiome.

<p>(a) 16S ribosomal RNA genes in cecal stool samples of female mice. Each bar represents one mouse. Phyla (Bacterioidetes, Firmicutes, or other) are classified into genus or unclassified family members. Further breakdown of composition within each phylum can be found in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0087181#pone-0087181-t002" target="_blank">Table 2</a>. (b-f) Cytokine production from female excised colons stimulated with LPS for 24–72 hours (n = 4–6). (g) Cytokine production from male splenocytes stimulated with LPS for 24–72 hours (n = 4–6). Results are representative of 2–3 independent experiments in BALB/c mice and displayed as mean+s.e.m. Significance determined by t test. All experiments were repeated with similar results in both genders. Gender is indicated when representative experiments are shown; otherwise, data reflects both male and female mice with matched ratios within experiments. n designates number of mice per experiment. The results from the Low Fat group shown in (a) are a subset of what was previously reported in reference 13. The remaining data is novel.</p

Summary of study design.

<p>(a) For experiments evaluating the effects of parental diet, littermate mice were placed on either Low Fat or high omega-3 formulations one day prior to being placed in breeding cages. Breeder mice were maintained on the different diets throughout gestation and nursing. When the pups were three weeks post-partum, they were weaned to new cages. All pups were weaned onto the Low Fat control diet. Two to four weeks after weaning, the mice were evaluated in the described models. (b) For evaluation of the effects of active diet consumption, the converse experiment was performed. Pups from breeders on the Low Fat control diet were weaned into new cages and placed on either the omega-3 or Low Fat control diet. Figure modified from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0087181#pone.0087181-Myles1" target="_blank">[13]</a>.</p

Omega-3 consumption altered MRSA susceptibility.

<p>(a) Survival after infection with <i>E. coli</i> 01 K18 in pups of breeders exposed to LF or n−3 diet (n = 10–12). (b–g) <i>Staphylococcus aureus</i> (MRSA USA300) skin infection in male BALB/c mice. Lesion sizes (b), CFU (c), and mRNA expression in skin abscess tissue normalized against LF controls (dotted line) (d) (n = 5–6) in offspring mice. Lesion sizes (e), CFU (f), and mRNA expression in skin abscess tissue normalized against LF controls (dotted line) (g) (n = 10) in adult male mice. Results are representative of two (d and g) or combined from 2–3 (a–c and e–f) independent experiments and displayed as mean+s.e.m. Significance determined by t test (b–c, e–f), ANOVA with Bonferroni’s correction (d and g), or Kaplan-Meier (a). n designates mouse number per group.</p

High omega-3 intake altered allergic responses.

<p>(a–d) Weaned male BALB/c pups were gavaged with peanut protein and cholera toxin weekly for 4–8 weeks before challenge. Temperature drop after intraperitoneal challenge (a), total IgE (b), and peanut-specific antibodies (c and d) (n = 5). LF, Low Fat; n−3, Omega-3 diet. Results are representative of 2 or more (b-d) or combined from two (a) independent experiments and displayed as mean+s.e.m. Significance determined by t test. n designates mouse number per group per experiment.</p

n−3 pups had altered microbiomes.

<p>16S ribosomal RNA genes in cecal stool samples as percent of total yield. Pups from indicated breeder diets were weaned to LF diet either in cages with their littermates. Each column represents one mouse. The column order of mice mirrors the presentation in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0087181#pone-0087181-g002" target="_blank">Figure 2a</a>. LF, Low Fat; n−3, omega-3. Results are representative of 2 independent experiments. Significance determined by t test (phyla) or ANOVA with Bonferroni’s correction (genera): * = p value <0.05, ** = <0.01, *** = <0.001, – = not significant. The results from the Low Fat group shown in this table are a subset of what was previously reported in reference 13. The remaining data is novel.</p