Omega-3 Fatty Acid and Iron Supplementation Alone, but Not in Combination, Lower Inflammation and Anemia of Infection in Mycobacterium tuberculosis-Infected Mice.

Progressive inflammation and anemia are common in tuberculosis (TB) and linked to poor clinical outcomes. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have inflammation-resolving properties, whereas iron supplementation in TB may have limited efficacy and enhance bacterial growth. We investigated effects of iron and EPA/DHA supplementation, alone and in combination, on inflammation, anemia, iron status markers and clinical outcomes in Mycobacterium tuberculosis-infected C3HeB/FeJ mice. One week post-infection, mice received the AIN-93 diet without (control) or with supplemental iron (Fe), EPA/DHA, or Fe+EPA/DHA for 3 weeks. Mice supplemented with Fe or EPA/DHA had lower soluble transferrin receptor, ferritin and hepcidin than controls, but these effects were attenuated in Fe+EPA/DHA mice. EPA/DHA increased inflammation-resolving lipid mediators and lowered lung IL-1α, IFN-γ, plasma IL-1ß, and TNF-α. Fe lowered lung IL-1α, IL-1ß, plasma IL-1ß, TNF-α, and IL-6. However, the cytokine-lowering effects in the lungs were attenuated with Fe+EPA/DHA. Mice supplemented with EPA/DHA had lower lung bacterial loads than controls, but this effect was attenuated in Fe+EPA/DHA mice. Thus, individually, post-infection EPA/DHA and iron supplementation lowered systemic and lung inflammation and mitigated anemia of infection in TB, but not when combined. EPA/DHA also enhanced bactericidal effects and could support inflammation resolution and management of anemia.

Oral iron exacerbates colitis and influences the intestinal microbiome.

Inflammatory bowel disease (IBD) is associated with anaemia and oral iron replacement to correct this can be problematic, intensifying inflammation and tissue damage. The intestinal microbiota also plays a key role in the pathogenesis of IBD, and iron supplementation likely influences gut bacterial diversity in patients with IBD. Here, we assessed the impact of dietary iron, using chow diets containing either 100, 200 or 400 ppm, fed ad libitum to adult female C57BL/6 mice in the presence or absence of colitis induced using dextran sulfate sodium (DSS), on (i) clinical and histological severity of acute DSS-induced colitis, and (ii) faecal microbial diversity, as assessed by sequencing the V4 region of 16S rRNA. Increasing or decreasing dietary iron concentration from the standard 200 ppm exacerbated both clinical and histological severity of DSS-induced colitis. DSS-treated mice provided only half the standard levels of iron ad libitum (i.e. chow containing 100 ppm iron) lost more body weight than those receiving double the amount of standard iron (i.e. 400 ppm); p<0.01. Faecal calprotectin levels were significantly increased in the presence of colitis in those consuming 100 ppm iron at day 8 (5.94-fold) versus day-10 group (4.14-fold) (p<0.05), and for the 400 ppm day-8 group (8.17-fold) versus day-10 group (4.44-fold) (p<0.001). In the presence of colitis, dietary iron at 400 ppm resulted in a significant reduction in faecal abundance of Firmicutes and Bacteroidetes, and increase of Proteobacteria, changes which were not observed with lower dietary intake of iron at 100 ppm. Overall, altering dietary iron intake exacerbated DSS-induced colitis; increasing the iron content of the diet also led to changes in intestinal bacteria diversity and composition after colitis was induced with DSS.

Effects of Dietary Iron Modulation on Gut Microbial Composition and Function in Monogastrics: A Review.

Dietary iron is a crucial nutrient element for biological processes of both hosts and gut microbiota. Deficiency in dietary iron is a highly common disorder in the developing locations of the world and can be healed by oral iron administration or complementary iron diet. While the redundant iron that enters the gut lumen leads to negative effects, and modulates the gut microbial composition and function. Such modulation led to a significant effect on vital biological pathways of the host, including metabolic disease (obesity and type 2 diabetes), metabolites (SCFA, blood glucose and cholesterol), bile acid metabolism, endocrine, neural, and other well-being patterns. This review covers the multifaceted aspects of different nutritional iron stress on the composition and function of microbial gut in monogastrics and consequential health conditions as well as it reveals unclear points that need further studies.

Intravenous Iron Carboxymaltose as a Potential Therapeutic in Anemia of Inflammation.

Intravenous iron supplementation is an effective therapy in iron deficiency anemia (IDA), but controversial in anemia of inflammation (AI). Unbound iron can be used by bacteria and viruses for their replication and enhance the inflammatory response. Nowadays available high molecular weight iron complexes for intravenous iron substitution, such as ferric carboxymaltose, might be useful in AI, as these pharmaceuticals deliver low doses of free iron over a prolonged period of time. We tested the effects of intravenous iron carboxymaltose in murine AI: Wild-type mice were exposed to the heat-killed Brucella abortus (BA) model and treated with or without high molecular weight intravenous iron. 4h after BA injection followed by 2h after intravenous iron treatment, inflammatory cytokines were upregulated by BA, but not enhanced by iron treatment. In long term experiments, mice were fed a regular or an iron deficient diet and then treated with intravenous iron or saline 14 days after BA injection. Iron treatment in mice with BA-induced AI was effective 24h after iron administration. In contrast, mice with IDA (on iron deficiency diet) prior to BA-IA required 7d to recover from AI. In these experiments, inflammatory markers were not further induced in iron-treated compared to vehicle-treated BA-injected mice. These results demonstrate that intravenous iron supplementation effectively treated the murine BA-induced AI without further enhancement of the inflammatory response. Studies in humans have to reveal treatment options for AI in patients.

Increased hepcidin expression in multibacillary leprosy

Iron is essential for all organisms and its availability can control the growth of microorganisms; therefore, we examined the role of iron metabolism in multibacillary (MB) leprosy, focusing on the involvement of hepcidin. Erythrograms, iron metabolism parameters, pro-inflammatory cytokines and urinary hepcidin levels were evaluated in patients with MB and matched control subjects. Hepcidin expression in MB lesions was evaluated by quantitative polymerase chain reaction. The expression of ferroportin and hepcidin was evaluated by immunofluorescence in paucibacillary and MB lesions. Analysis of hepcidin protein levels in urine and of hepcidin mRNA and protein levels in leprosy lesions and skin biopsies from healthy control subjects showed elevated hepcidin levels in MB patients. Decreases in haematologic parameters and total iron binding capacity were observed in patients with MB leprosy. Moreover, interleukin-1 beta, ferritin, soluble transferrin receptor and soluble transferrin receptor/log ferritin index values were increased in leprosy patients. Hepcidin was elevated in lepromatous lesions, whereas ferroportin was more abundant in tuberculoid lesions. In addition, hepcidin and ferroportin were not colocalised in the biopsies from leprosy lesions. Anaemia was not commonly observed in patients with MB; however, the observed changes in haematologic parameters indicating altered iron metabolism appeared to result from a mixture of anaemia of inflammation and iron deficiency. Thus, iron sequestration inside host cells might play a role in leprosy by providing an optimal environment for the bacillus.

Nanotransformation of the haemotrophic Mycoplasma suis during in vitro cultivation attempts using modified cell free Mycoplasma media.

Mycoplasma suis belongs to haemotrophic mycoplasmas (HMs) which cause infectious anaemia in a large variety of mammals. To date, no in vitro cultivation system for M. suis or other HMs has been established. We hypothesised that M. suis could grow in classical Mycoplasma media supplemented with nutrients (e.g. glucose, iron-binding proteins) which are naturally available from its host environment, the porcine blood. Blood from experimentally M. suis-infected pigs was used to inoculate either standard SP-4 Mycoplasma medium supplemented with iron-binding proteins (transferrin, haemin, and haemoglobin) or glucose-enriched Hayflick Mycoplasma medium. A quantitative M. suis-specific real-time PCR assay was applied to determine and quantify M. suis loads weekly during 12 week-incubation. The first 2 weeks after inoculation M. suis loads decreased remarkably and then persisted at a stationary level over the observation time of 12 weeks in iron-binding protein- or glucose supplemented media variants. Scanning electron microscopic analysis of liquid M. suis sub-cultures on Hayflick agar showed small, densely-packed microcolonies of irregular M. suis cells of reduced size (0.2-0.6µm) indicating nanotransformation. The partial 16S rDNA sequence of these cultured M. suis nanocells was 99.9% identical to M. suis. M. suis cells derived from liquid cultures interact in vitro with porcine erythrocytes by fibril-like structures. We conclude, that the modified Mycoplasma media used for M. suis cultivation are obviously unfavourable for growth but lead to culture persistence. M. suis adapt to inappropriate culture conditions by alteration into nanoforms.

Increased hepcidin expression in multibacillary leprosy.

Iron is essential for all organisms and its availability can control the growth of microorganisms; therefore, we examined the role of iron metabolism in multibacillary (MB) leprosy, focusing on the involvement of hepcidin. Erythrograms, iron metabolism parameters, pro-inflammatory cytokines and urinary hepcidin levels were evaluated in patients with MB and matched control subjects. Hepcidin expression in MB lesions was evaluated by quantitative polymerase chain reaction. The expression of ferroportin and hepcidin was evaluated by immunofluorescence in paucibacillary and MB lesions. Analysis of hepcidin protein levels in urine and of hepcidin mRNA and protein levels in leprosy lesions and skin biopsies from healthy control subjects showed elevated hepcidin levels in MB patients. Decreases in haematologic parameters and total iron binding capacity were observed in patients with MB leprosy. Moreover, interleukin-1 beta, ferritin, soluble transferrin receptor and soluble transferrin receptor/log ferritin index values were increased in leprosy patients. Hepcidin was elevated in lepromatous lesions, whereas ferroportin was more abundant in tuberculoid lesions. In addition, hepcidin and ferroportin were not colocalised in the biopsies from leprosy lesions. Anaemia was not commonly observed in patients with MB; however, the observed changes in haematologic parameters indicating altered iron metabolism appeared to result from a mixture of anaemia of inflammation and iron deficiency. Thus, iron sequestration inside host cells might play a role in leprosy by providing an optimal environment for the bacillus.

Use of pradofloxacin to treat experimentally induced Mycoplasma hemofelis infection in cats.

OBJECTIVE: To evaluate the efficacy of the fluoroquinolone pradofloxacin in the treatment of cats experimentally infected with Mycoplasma hemofelis. ANIMALS: 23 young adult specific-pathogen-free cats. PROCEDURES: Cats were inoculated with M hemofelis from a chronically infected donor and assigned to 1 of 4 treatment groups: a doxycycline group, a low-dose-pradofloxacin group, a high-dose-pradofloxacin group, and an untreated control group. Treatment was initiated for 14 days when M hemofelis infection was detected via PCR assay and clinical signs of hemoplasmosis were present. Cats that had negative PCR assay results after treatment were administered a glucocorticoid and monitored via PCR assay for an additional 4 weeks. RESULTS: All cats yielded positive results for M hemofelis via conventional PCR and quantitative PCR assays and developed anemia. The low-dose-pradofloxacin group had significantly lower M hemofelis copy numbers than the doxycycline group. Six cats treated with pradofloxacin yielded negative results during treatment. Of those cats, 4 yielded negative conventional PCR assay results and all yielded negative quantitative PCR assay results for M hemofelis 1 month after administration of high-dose glucocorticoids. CONCLUSIONS AND CLINICAL RELEVANCE: Pradofloxacin had anti-M hemofelis effects similar to those of doxycycline. In addition, pradofloxacin may be more effective at long-term M hemofelis organism clearance than doxycycline.

Increased plasma malondialdehyde and fructosamine in anemic H pylori infected patients: effect of treatment.

AIM: To unravel the possible association of malondialdehyde (MDA) and fructosamine in anemic H pylori infected patients and to observe the alteration in MDA and fructosamine levels in these patients after treatment for one month. METHODS: Fructosamine, MDA and glucose were estimated in 22 anemic H pylori infected patients and 16 healthy controls. Hematological parameters were also evaluated in both the groups using Sysmex-K-100 automated cell counter. The H pylori infected patients were randomly divided into two groups. H pylori infected patients in Group I received both iron supplementation and anti-H pylori therapy, while patients in Group II received only iron supplementation. All the biochemical and hematological parameters were estimated after one month of treatment. RESULTS: In anemic H pylori infected patients, while MDA (5.41 +/- 2.16 vs 2.26 +/- 0.50; P < 0.05) and fructosamine (2.64 +/- 0.93 vs 1.60 +/- 0.35; P < 0.05) were significantly increased, iron (32.72 +/- 14.93 vs 110.25 +/- 26.58; P < 0.05), hemoglobin (6.9 +/- 2.6 vs 12.66 +/- 0.74; P < 0.05) and ferritin (28.82 +/- 16.27 vs 140.43 +/- 30.72; P < 0.05) levels were significantly decreased compared with the controls. With partial correlation analysis, fructosamine was found to have a significant positive correlation with MDA. In Group I, while MDA level decreased significantly (3.11 +/- 1.73 vs 5.50 +/- 2.46; P < 0.05), there was a significant increase in iron (84.09 +/- 29.51 vs 36.09 +/- 17.81; P < 0.05), hemoglobin (10.40 +/- 1.11 vs 7.42 +/- 1.90; P < 0.05) and ferritin (116.91 +/- 63.34 vs 30.46 +/- 17.81; P < 0.05) levels after one month. There was no significant change in the levels of fructosamine in group I after treatment. Similarly, no significant alterations were noted in the levels of MDA, fructosamine, hemoglobin or ferritin in Group II patients after one month of treatment. CONCLUSION: An increased level of fructosamine and MDA was found in anemic H pylori infected patients. Present data supports the premise that lipid peroxides per se do play a role in the glycation of plasma proteins. Furthermore, the findings from this study indicate that treatment for both anemia and H pylori infections is required for lowering the levels of lipid peroxides in these patients.