Adjunct n-3 Long-Chain Polyunsaturated Fatty Acid Treatment in Tuberculosis Reduces Inflammation and Improves Anemia of Infection More in C3HeB/FeJ Mice With Low n-3 Fatty Acid Status Than Sufficient n-3 Fatty Acid Status

Populations at risk for tuberculosis (TB) may have a low n-3 polyunsaturated fatty acid (PUFA) status. Our research previously showed that post-infection supplementation of n-3 long-chain PUFA (LCPUFA) in TB without TB medication was beneficial in n-3 PUFA sufficient but not in low-status C3HeB/FeJ mice. In this study, we investigated the effect of n-3 LCPUFA adjunct to TB medication in TB mice with a low compared to a sufficient n-3 PUFA status. Mice were conditioned on an n-3 PUFA-deficient (n-3FAD) or n-3 PUFA-sufficient (n-3FAS) diet for 6 weeks before TB infection. Post-infection at 2 weeks, both groups were switched to an n-3 LCPUFA [eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA)] supplemented diet and euthanized at 4- and 14- days post-treatment. Iron and anemia status, bacterial loads, lung pathology, lung cytokines/chemokines, and lung lipid mediators were measured. Following 14 days of treatment, hemoglobin (Hb) was higher in the n-3FAD than the untreated n-3FAS group (p = 0.022), whereas the n-3FAS (drug) treated control and n-3FAS groups were not. Pro-inflammatory lung cytokines; interleukin-6 (IL-6) (p = 0.011), IL-1α (p = 0.039), MCP1 (p = 0.003), MIP1- α (p = 0.043), and RANTES (p = 0.034); were lower, and the anti-inflammatory cytokine IL-4 (p = 0.002) and growth factor GMCSF (p = 0.007) were higher in the n-3FAD compared with the n-3FAS mice after 14 days. These results suggest that n-3 LCPUFA therapy in TB-infected mice, in combination with TB medication, may improve anemia of infection more in low n-3 fatty acid status than sufficient status mice. Furthermore, the low n-3 fatty acid status TB mice supplemented with n-3 LCPUFA showed comparatively lower cytokine-mediated inflammation despite presenting with lower pro-resolving lipid mediators.

AMINO ACID STATUS OF BOVINE MILK UNDER SEASONAL VARIATION AROUND SINGRAULI DISTRICT

Objective: The present work deals with the concerned study to determine the influence of variable season on amino acid evaluation from 90 bovine milk collected (March 2018 to February 2019) samples belongs to four tehsils of Singrauli district. Methods: An aliquot of hydrolysate of collected bovine milk samples were injected into the column (Shim-pack ISC-07/S1504 Na) of the higher performance liquid chromatography-based amino acid analyzer. Results: Most abundant amino acids were glutamic acid followed by proline and leucine. Average amino acid content comparison, results, in the rainy season, maximum amino acid content was in Deosar and minimum in Singrauli, In winter amino acid is higher in Waidhan and minimum in Deosar and maximum amino acid content was recorded intended for Waidhan and minimum for Deosar in summer. Concentration of amino acid in cow milk was found to be in order of glycine<histidine<alanine<methionine<isoleucine<phenylalanine<threonine<tyrosine<serine<lysine<valine and aspartic acid<arginine<leucine<proline<glutamic acid. Amino acid status in buffalo milk sample was found in order Glycine<histidine<methionine<alanine<phenylalanine<isoleucine<threonine<arginine<tyrosine<serine and lysine<aspartic acid<valine<leucine<proline<glutamic acid. All the amino acids are evaluated as per the mean (n = 6) mean±SD. Conclusion: It is concluded that cow and buffalo milk samples contained all the amino acids but differed in the contents of certain amino acids. Such variation is purely biological and genetic and is intended for the nourishment of the young. The current investigation would be valuable for the dairy processing industries to formulate nutritionally improved milk-based functional products for a vulnerable segment of the population.

Omega-3 long-chain polyunsaturated fatty acids promote antibacterial and inflammation-resolving effects in Mycobacterium tuberculosis-infected C3HeB/FeJ mice, dependent on fatty acid status

Non-resolving inflammation is characteristic of tuberculosis (TB). Given their inflammation-resolving properties, omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) may support TB treatment. This research aimed to investigate the effects of n-3 LCPUFA on clinical and inflammatory outcomes of Mycobacterium tuberculosis (Mtb)-infected C3HeB/FeJ mice with either normal or low n-3 PUFA status before infection. Using a two-by-two design, uninfected mice were conditioned on either an n-3 PUFA-sufficient (n-3FAS) or -deficient (n3FAD) diet for six weeks. One week post-infection, mice were randomised to either n-3 LCPUFA supplemented (n-3FAS/n-3+ and n3FAD/n3+) or continued on n-3FAS or n3FAD diets for three weeks. Mice were euthanised and fatty acid status, lung bacterial load and pathology, cytokine, lipid mediator, and immune cell phenotype analysed. n-3 LCPUFA supplementation in n-3FAS mice lowered lung bacterial loads (P=0·003), T cells (P=0·019), CD4+ T cells (P=0·014), IFN-γ (P<0·001) and promoted a pro-resolving lung lipid mediator profile. Compared with n-3FAS mice, the n-3FAD group had lower bacterial loads (P=0·037), significantly higher immune cell recruitment and a more pro-inflammatory lipid mediator profile, however, significantly lower lung IFN-γ, IL-1α, IL-1β, and IL-17, and supplementation in the n-3FAD group provided no beneficial effect on lung bacterial load or inflammation. Our study provides the first evidence that n-3 LCPUFA supplementation has antibacterial and inflammation-resolving benefits in TB when provided one week after infection in the context of a sufficient n-3 PUFA status. Whilst a low n-3 PUFA status may promote better bacterial control and lower lung inflammation not benefiting from n-3 LCPUFA supplementation.

Sulfur amino acids status controls selenium methylation in Pseudomonas tolaasii: Identification of a novel metabolite from promiscuous enzyme reactions

Selenium (Se) deficiency affects many millions of people worldwide, and the volatilization of methylated Se species to the atmosphere may prevent Se from entering the food chain. Despite the extent of Se deficiency, little is known about fluxes in volatile Se species and their temporal and spatial variation in the environment, giving rise to uncertainty in atmospheric transport models. To systematically determine fluxes, one can rely on laboratory microcosm experiments to quantify Se volatilization in different conditions. Here, it is demonstrated that the sulfur (S) status of bacteria crucially determines the amount of Se volatilized. Solid phase microextraction gas chromatography mass spectrometry showed that Pseudomonas tolaasii efficiently and rapidly (92% in 18h) volatilized Se to dimethyldiselenide and dimethylselenylsulfide through promiscuous enzymatic reactions with the S metabolism. However, when the cells were supplemented with cystine (but not methionine), a major proportion of the Se (∼48%) was channelled to thus far unknown, non-volatile Se compounds at the expense of the previously formed dimethyldiselenide and dimethylselenylsulfide (accounting for < 4% of total Se). Ion chromatography and solid phase extraction were used to isolate unknowns, and electrospray ionization ion trap mass spectrometry, electrospray ionization quadrupole time-of-flight mass spectrometry and microprobe nuclear magnetic resonance spectrometry were used to identify the major unknown as a novel Se metabolite, 2-hydroxy-3-(methylselanyl)propanoic acid. Environmental S concentrations often exceed Se concentrations by orders of magnitude. This suggests that in fact S status may be a major control on selenium fluxes to the atmosphere. Importance Volatilization from soil to the atmosphere is a major driver for Se deficiency. "Bottom up" models for atmospheric Se transport are based on laboratory experiments quantifying volatile Se compounds. The high Se and low S concentrations in such studies poorly represent the environment. Here, we show that S amino acid status has in fact a decisive effect on the production of volatile Se species in Pseudomonas tolaasii. When the strain was supplemented with S amino acids, a major proportion of the Se was channelled to thus far unknown, non-volatile Se compounds at the expense of volatile compounds. This hierarchical control of the microbial S amino acid status on Se cycling has been thus far neglected. Understanding these interactions – if occurring in the environment- will help to improve atmospheric Se models and thus predict drivers of Se deficiency.