Modulation of gut microbiota from obese individuals by in vitro fermentation of citrus pectin in combination with Bifidobacterium longum BB-46

This study aimed to evaluate the effects of three treatments, i.e., Bifidobacterium longum BB-46 (T1), B. longum BB-46 combined with the pectin (T2), and harsh extracted pectin from lemon (T3) on obesity-related microbiota using the Simulator of the Human Intestinal Microbial Ecosystem (SHIME®). The effects of the treatments were assessed by the analysis of the intestinal microbial composition (using 16S rRNA gene amplicon sequencing) and the levels of short-chain fatty acids (SCFAs) and ammonium ions (NH₄⁺). Treatments T2 and T3 stimulated members of the Ruminococcaceae and Succinivibrionaceae families, which were positively correlated with an increase in butyric and acetic acids. Proteolytic bacteria were reduced by the two treatments, concurrently with a decrease in NH₄⁺. Treatment T1 stimulated the production of butyric acid in the simulated transverse and descending colon, reduction of NH₄⁺ as well as the growth of genera Lactobacillus, Megamonas, and members of Lachnospiracea. The results indicate that both B. longum BB-46 and pectin can modulate the obesity-related microbiota; however, when the pectin is combined with B. longum BB-46, the predominant effect of the pectin can be observed. This study showed that the citric pectin is able to stimulate butyrate-producing bacteria as well as genera related with anti-inflammatory effects. However, prospective clinical studies are necessary to evaluate the anti/pro-obesogenic and inflammatory effects of this pectin for future prevention of obesity.

     

Morphological and biochemical characterization of the cutaneous poison glands in toads (<Emphasis Type="Italic">Rhinella marina</Emphasis> group) from different environments

Background

Amphibian defence against predators and microorganisms is directly related to cutaneous glands that produce a huge number of different toxins. These glands are distributed throughout the body but can form accumulations in specific regions. When grouped in low numbers, poison glands form structures similar to warts, quite common in the dorsal skin of bufonids (toads). When accumulated in large numbers, the glands constitute protuberant structures known as macroglands, among which the parotoids are the most common ones. This work aimed at the morphological and biochemical characterization of the poison glands composing different glandular accumulations in four species of toads belonging to group Rhinella marina (R. icterica, R. marina, R. schneideri and R. jimi). These species constitute a good model since they possess other glandular accumulations together with the dorsal warts and the parotoids and inhabit environments with different degrees of water availability.

Results

We have observed that the toads skin has three types of poison glands that can be differentiated from each other through the morphology and the chemical content of their secretion product. The distribution of these different glands throughout the body is peculiar to each toad species, except for the parotoids and the other macroglands, which are composed of an exclusive gland type that is usually different from that composing the dorsal warts. Each type of poison gland presents histochemical and biochemical peculiarities, mainly regarding protein components.

Conclusions

The distribution, morphology and chemical composition of the different types of poison glands, indicate that they may have different defensive functions in each toad species.

     

Viral Phylodynamics

Viral phylodynamics is defined as the study of how epidemiological, immunological, and evolutionary processes act and potentially interact to shape viral phylogenies. Since the coining of the term in 2004, research on viral phylodynamics has focused on transmission dynamics in an effort to shed light on how these dynamics impact viral genetic variation. Transmission dynamics can be considered at the level of cells within an infected host, individual hosts within a population, or entire populations of hosts. Many viruses, especially RNA viruses, rapidly accumulate genetic variation because of short generation times and high mutation rates. Patterns of viral genetic variation are therefore heavily influenced by how quickly transmission occurs and by which entities transmit to one another. Patterns of viral genetic variation will also be affected by selection acting on viral phenotypes. Although viruses can differ with respect to many phenotypes, phylodynamic studies have to date tended to focus on a limited number of viral phenotypes. These include virulence phenotypes, phenotypes associated with viral transmissibility, cell or tissue tropism phenotypes, and antigenic phenotypes that can facilitate escape from host immunity. Due to the impact that transmission dynamics and selection can have on viral genetic variation, viral phylogenies can therefore be used to investigate important epidemiological, immunological, and evolutionary processes, such as epidemic spread [2], spatio-temporal dynamics including metapopulation dynamics [3], zoonotic transmission, tissue tropism [4], and antigenic drift [5]. The quantitative investigation of these processes through the consideration of viral phylogenies is the central aim of viral phylodynamics.

This is a “Topic Page” article for PLOS Computational Biology.

     

TNF-α and CD8+ T Cells Mediate the Beneficial Effects of Nitric Oxide Synthase-2 Deficiency in Pulmonary Paracoccidioidomycosis

Background

Nitric oxide (NO), a key antimicrobial molecule, was previously shown to exert a dual role in paracoccidioidomycosis, an endemic fungal infection in Latin America. In the intravenous and peritoneal models of infection, NO production was associated with efficient fungal clearance but also with non-organized granulomatous lesions. Because paracoccidioidomycosis is a pulmonary infection, we aimed to characterize the role of NO in a pulmonary model of infection.

Methodology/Principal Findings

C57Bl/6 wild type (WT) and iNOS^−/− mice were i.t. infected with 1×10⁶ Paracoccidioides brasiliensis yeasts and studied at several post-infection periods. Unexpectedly, at week 2 of infection, iNOS^−/− mice showed decreased pulmonary fungal burdens associated with an M2-like macrophage profile, which expressed high levels of TGF-β impaired ability of ingesting fungal cells. This early decreased fungal loads were concomitant with increased DTH reactions, enhanced TNF-α synthesis and intense migration of activated macrophages, CD4⁺ and CD8⁺ T cells into the lungs. By week 10, iNOS^−/− mice showed increased fungal burdens circumscribed, however, by compact granulomas containing elevated numbers of activated CD4⁺ T cells. Importantly, the enhanced immunological reactivity of iNOS^−/− mice resulted in decreased mortality rates. In both mouse strains, depletion of TNF-α led to non-organized lesions and excessive influx of inflammatory cells into the lungs, but only the iNOS^−/− mice showed increased mortality rates. In addition, depletion of CD8⁺ cells abolished the increased migration of inflammatory cells and decreased the number of TNF-α and IFN-γ CD4⁺ and CD8⁺ T cells into the lungs of iNOS^−/− mice.

Conclusions/Significance

Our study demonstrated that NO plays a deleterious role in pulmonary paracoccidioidomycosis due to its suppressive action on TNF-α production, T cell immunity and organization of lesions resulting in precocious mortality of mice. It was also revealed that uncontrolled fungal growth can be overcome by an efficient immune response.     

The Risk of Familial Mediterranean Fever in MEFV Heterozygotes: A Statistical Approach

Background

Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disorder due to MEFV mutations and one of the most frequent Mediterranean genetic diseases. The observation of many heterozygous patients in whom a second mutated allele was excluded led to the proposal that heterozygosity could be causal. However, heterozygosity might be coincidental in many patients due to the very high rate of mutations in Mediterranean populations.

Objective

To better delineate the pathogenicity of heterozygosity in order to improve genetic counselling and disease management.

Methods

Complementary statistical approaches were used: estimation of FMF prevalence at population levels, genotype comparison in siblings from 63 familial forms, and genotype study in 557 patients from four Mediterranean populations.

Results

At the population level, we did not observe any contribution of heterozygosity to disease prevalence. In affected siblings of patients carrying two MEFV mutations, 92% carry two mutated alleles, whereas 4% are heterozygous with typical FMF diagnosis. We demonstrated statistically that patients are more likely to be heterozygous than healthy individuals, as shown by the higher ratio heterozygous carriers/non carriers in patients (p<10⁻⁷–p<0.003). The risk for heterozygotes to develop FMF was estimated between 2.1×10⁻³ and 5.8×10⁻³ and the relative risk, as compared to non carriers, between 6.3 and 8.1.

Conclusions

This is the first statistical demonstration that heterozygosity is not responsible for classical Mendelian FMF per se, but constitutes a susceptibility factor for clinically-similar multifactorial forms of the disease. We also provide a first estimate of the risk for heterozygotes to develop FMF.     

Autoimmune Memory T Helper 17 Cell Function and Expansion Are Dependent on Interleukin-23

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Can arsenic-phytochelatin complex formation be used as an indicator for toxicity in Helianthus annuus?

The formation of arsenic-phytochelatin (As-PC) complexes is thought to be part of the plant detoxification strategy for arsenic. This work examines (i) the arsenic (As) concentration-dependent formation of As-PC complex formation and (ii) redistribution and metabolism of As after arrested As uptake in Helianthus annuus. HPLC with parallel ICP-MS/ES-MS detection was used to identify and quantify the species present in plant extracts exposed to arsenate (As(V)) (between 0 and 66.7 micromol As l-1 for 24 h). At As concentrations below the EC50 value for root growth (22 micromol As l-1) As uptake is exponential, but it is reduced at concentrations above. Translocation between root and shoot seemed to be limited to the uptake phase of arsenic. No redistribution of As between root and shoot was observed after arresting As exposure. The formation of As-PC complexes was concentration-dependent. The amount and number of As-PC complexes increased exponentially with concentration up to 13.7 micromol As l-1. As(III)-PC3 and GS-As(III)-PC2 complexes were the dominant species in all samples. The ratio of PC-bound As to unbound As increased up to 1.3 micromol As l-1 and decreased at higher concentrations. Methylation of inorganic As was only a minor pathway in H. annuus with about 1% As methylated over a 32 d period. The concentration dependence of As-PC complex formation, amount of unbound reduced and oxidized PC2, and the relative uptake rate showed that As starts to influence the cellular metabolism of H. annuus negatively at As concentrations well below the EC50 value determined by more traditional means. Generally, As-PC complexes and PC-synthesis rate seem to be the more sensitive parameters to be studied when As toxicity values are to be estimated.