Limit iron intake to limit growth of invading pathogens

iron.pngIron Limitation as an Innate Immune Defense

In addition to mitigating toxicity associated with hypo- or hyperferremia, regulation of iron distribution serves as an innate immune mechanism against invading pathogens. Even in the absence of infection, several facets of human iron metabolism ensure that iron is scarcely accessible to pathogenic microorganisms. First, the majority of iron in humans is sequestered intracellularly, complexed within hemoglobin inside erythrocytes. Some pathogens have therefore evolved mechanisms to liberate hemoglobin by lysing erythrocytes to ultimately extract iron from heme. However, hemolytic pathogens must subsequently compete with haptoglobin and hemopexin, host glycoproteins that scavenge liberated hemoglobin and heme, respectively (Figure 1D). A second factor limiting the availability of iron to invading pathogens is the paucity of free extracellular iron. Extracellular iron is bound with high affinity by transferrin, which in healthy individuals is typically less than 50% saturated with iron. When transferrin-binding capacity is exceeded, iron can also be chelated with lower affinity by a number of molecules in plasma including albumin, citrate, and amino acids (Nathan et al., 2003).

During infection, additional fortification of iron-withholding defense occurs (Figure 2). The hypoferremia of infection was documented in seminal studies by Cartwright et al. in the 1940s, who noted a precipitous drop in plasma iron levels upon intramuscular inoculation of canines with Staphylococcus aureus. A similar hypoferremic response was noted upon intravenous injection with sterile turpentine, suggesting that inflammation, rather than a specific microbial product, was responsible for declining plasma iron levels (Cartwright et al., 1946). Since these initial observations, much has been learned regarding the importance of iron withholding to the outcome of host-pathogen interactions.

https://www.sciencedirect.com/science/article/pii/S1931312813001522

 

With the oxygenation of the Earth’s atmosphere over 2 billion years ago, abundant soluble Fe2+ was oxidized to insoluble Fe3+, making bioavailable iron much more scarce. At the same time, iron became potentially more toxic since the redox cycling of iron in the presence of oxygen and hydrogen peroxide catalyzes the production of free radicals in the Fenton reaction that can damage DNA, protein, and lipids.Humans and other organisms therefore evolved specialized proteins and tightly regulated homeostatic mechanisms for the uptake, transport, storage, and export of iron to provide adequate iron for essential biologic process, but to limit the toxicity of iron excess.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5977983/

Brain iron loading impairs DNA methylation and alters GABAergic function in mice.

https://www.fasebj.org/doi/abs/10.1096/fj.201801116RR?journalCode=fasebj

The term “hemochromatosis,” introduced by von Recklinghausen at the end of the 19th century, refers to the clinical disorder that results from excess of total body iron and organ failure due to iron toxicity. The disease manifestations include cirrhosis, diabetes mellitus, hypogonadism and other endocrinopathies, cardiomyopathy, arthropathy, skin pigmentation, and, in cirrhotic patients, increased susceptibility to liver cancer.

http://www.bloodjournal.org/content/106/12/3710?sso-checked=true

Monthly brain cycles predict seizures in patients with epilepsy

Other studies:
Yoga is believed to induce relaxation and stress reduction. The effect of yoga on the EEG and the autonomic nervous system have been reported.
A musicogenic seizure is reflex epilepsy triggered by certain types of music or even specific frequencies of pitch for which the person’s brain has a low threshold or tolerance. These sounds trigger focal epileptiform EEG discharges in cerebral areas specific to the triggering stimulus.
People with epilepsy appear to have decreased parasympathetic tone, with a greater decrease in those with intractable seizures than in those with well-controlled epilepsy. Slow breathingexercises have been shown to increase parasympathetic tone in healthy volunteers.

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Gut Bacteria Linked to Age Related Conditions

Gut Bacteria Linked to Age Related Conditions

Source: Frontiers.

A new study shows for the first time that gut bacteria from old mice induce age-related chronic inflammation when transplanted into young mice. Called “inflammaging,” this low-grade chronic inflammation is linked to life-limiting conditions such as stroke, dementia and cardiovasuclar disease. The research, published today in open-access journal Frontiers in Immunology, brings the hope of a potentially simple strategy to contribute to healthy ageing, as the composition of bacteria in the gut is, at least in part, controlled by diet.

“Since inflammaging is thought to contribute to many diseases associated with ageing, and we now find that the gut microbiota plays a role in this process, strategies that alter the gut microbiota composition in the elderly could reduce inflammaging and promote healthy ageing,” explains Dr Floris Fransen, who performed the research at the University Medical Center Groningen, The Netherlands. “Strategies that are known to alter gut microbiota composition include changes in diet, probiotics, and prebiotics.”

Previous research shows that the elderly tend to have a different composition of gut bacteria than younger people.

Immune responses also tend to be compromised in the elderly, resulting in inflammaging.

Knowing this, Fransen and his team set out to investigate a potential link.

The scientists transferred gut microbiota from old and young conventional mice to young germ-free mice, and analysed immune responses in their spleen, lymph nodes and tissues in the small intestine. They also analysed whole-genome gene expression in the small intestine.

All results showed an immune response to bacteria transferred from the old mice but not from the young mice.

The results suggest that an imbalance of the bacterial composition in the gut may be the cause of inflammaging in the elderly. Imbalances, or “dysbiosis” of gut bacteria results in “bad” bacteria being more dominant than “good” bacteria. An overgrowth of bad bacteria can make the lining of the gut become more permeable, allowing toxins to enter the bloodstream where they can travel around the body with various negative effects.

Dysbiosis can have serious health implications: several disorders, such as inflammatory bowel disease, obesity, diabetes, cancer, anxiety and autism are already linked to the condition.

“Our gut is inhabited by a huge number of bacteria” explains Fransen. “Moreover, there are many different kinds of bacterial species, and the bacterial species that are present can vary a lot from person to person.”

gut

Maintaining a healthy gut microbiota is clearly important to a healthy body and healthy ageing, but why the gut microbiota is different in the elderly is not fully understood. Many people are aware of the effect a course of antibiotics can have on the digestive system for example, but as Fransen explains, it may not be down to just one thing: “It is likely a combination of factors such as reduced physical activity, changes in diet, but also as part of a natural process.”

Most, if not all, age-related diseases can be linked back to inflammaging. Despite the fact that this particular study was conducted on mice, it is clear that maintaining a healthy gut microbiota is key to a healthy lifestyle. However, more research is needed to confirm that the human body mirrors the mice in this study.

“Both in humans and mice there is a correlation between altered gut microbiota composition and inflammaging, but the link between the two remains to be proven in humans” concludes Fransen.

The article is part of the Frontiers Research Topic Immunomodulatory Functions of Nutritional Ingredients in Health and Disease.

ABOUT THIS NEUROSCIENCE RESEARCH ARTICLE

Source: Frontiers
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Full open access research for “Aged Gut Microbiota Contributes to Systemical Inflammaging after Transfer to Germ-Free Mice” by Floris Fransen, Adriaan A. van Beek, Theo Borghuis, Sahar El Aidy, Floor Hugenholtz, Christa van der Gaast – de Jongh, Huub F. J. Savelkoul, Marien I. De Jonge, Mark V. Boekschoten, Hauke Smidt, Marijke M. Faas, and Paul de Vos in Frontiers in Immunology. Published online November 2 2017 doi:10.3389/fimmu.2017.01385

CITE THIS NEUROSCIENCENEWS.COM ARTICLE
Frontiers “Gut Bacteria Linked to Age Related Conditions.” NeuroscienceNews. NeuroscienceNews, 5 November 2017.
<http://neurosciencenews.com/microbiome-aging-inflammation-7878/&gt;.

Abstract

Aged Gut Microbiota Contributes to Systemical Inflammaging after Transfer to Germ-Free Mice

Advanced age is associated with chronic low-grade inflammation, which is usually referred to as inflammaging. Elderly are also known to have an altered gut microbiota composition. However, whether inflammaging is a cause or consequence of an altered gut microbiota composition is not clear. In this study, gut microbiota from young or old conventional mice was transferred to young germ-free (GF) mice. Four weeks after gut microbiota transfer immune cell populations in spleen, Peyer’s patches, and mesenteric lymph nodes from conventionalized GF mice were analyzed by flow cytometry. In addition, whole-genome gene expression in the ileum was analyzed by microarray. Gut microbiota composition of donor and recipient mice was analyzed with 16S rDNA sequencing. Here, we show by transferring aged microbiota to young GF mice that certain bacterial species within the aged microbiota promote inflammaging. This effect was associated with lower levels of Akkermansia and higher levels of TM7 bacteria and Proteobacteria in the aged microbiota after transfer. The aged microbiota promoted inflammation in the small intestine in the GF mice and enhanced leakage of inflammatory bacterial components into the circulation was observed. Moreover, the aged microbiota promoted increased T cell activation in the systemic compartment. In conclusion, these data indicate that the gut microbiota from old mice contributes to inflammaging after transfer to young GF mice.

“Aged Gut Microbiota Contributes to Systemical Inflammaging after Transfer to Germ-Free Mice” by Floris Fransen, Adriaan A. van Beek, Theo Borghuis, Sahar El Aidy, Floor Hugenholtz, Christa van der Gaast – de Jongh, Huub F. J. Savelkoul, Marien I. De Jonge, Mark V. Boekschoten, Hauke Smidt, Marijke M. Faas, and Paul de Vos in Frontiers in Immunology. Published online November 2 2017 doi:10.3389/fimmu.2017.01385