Starving those pathogens in the battle against diarrheal infections.

Nature abhors a vacuum. We can make evolutionary selection work for us to select beneficials and exclude nasty invaders.

The human microbiome may have 100 trillion microbes, composed of communities of bacteria, viruses and fungi. It has extensive functions such as development of immunity, defense against pathogens, host nutrition, production of short-chain fatty acids important in host energy metabolism, synthesis of vitamins and fat storage, even influence human behavior. This complex ecological community greatly affects us, and manipulation of the gut microbiome has potential use to treat diseases.

To Feed or Not to Feed

We usually lose our appetites when we feel sick. Is this a protective response? Or, is fasting-induced immunosuppression leaving an already fasted host more vulnerable to infection? Fasted mice were challenged with the invasive bacterium Salmonella Typhimurium, the pathogen that causes food poisoning. Salmonella bacteria proliferated in the intestines of the fed mice, but much less so in fasted mice. The fasted mice were also without intestinal tissue damage- bacteria were unable to invade their intestinal wall. But if you wipe out the microbiome in the fasted mice, protection disappears.

Hence, something in their microbiome colonies interacts along with the food restriction to thwart Salmonella. [Fucose may also be involved - see refs https://medicalxpress.com/news/2013-06-salmonella-infection-good-bad-bacteria.html]

Iron-restrictive Host Responses

In those biological niches where iron availability is low, microbes evolved mechanisms that allowed them to assimilate iron even at low ambient concentrations. But it costs them ‘metabolic energy’ to generate and operate. Hence, there is a balance between growth and stasis, based on the sum of nutrient iron available. To confer an evolutionary survival benefit, such costs must be outweighed by the advantages they confer in a particular niche. In niches where iron was more abundant, these mechanisms did not evolve or were lost. Evolutionary compromise requires encoded iron uptake tricks be activated by low environmental iron concentrations, conserving some of their metabolic costs until necessary.

The mechanism of hypoferremia of inflammation:

General inflammatory regulators are shown in grey, iron-regulatory pathway in green, iron flows in blue and erythropoiesis and erythrocytes in red

Fake sweets are fake food for biome

Okay, so we are supposed to fast and not feed if we get food poisoning. But what about drinking diet soda? Is that a good kind of fasting? Sorry, nope, even fake sugars make bad guys worse.

The present study sought to investigate the role of commonly consumed Artificial Sugars on gut bacterial pathogenicity and gut epithelium-microbiota interactions, using models of microbiota (Escherichia coli NCTC10418 and Enterococcus faecalis ATCC19433) and the intestinal epithelium (Caco-2 cells). Model gut bacteria were exposed to different concentrations of the AS saccharin, sucralose, and aspartame, and their pathogenicity and changes in interactions with Caco-2 cells were measured using in vitro studies. Findings show that sweeteners differentially increase the ability of bacteria to form a biofilm. Co-culture with human intestinal epithelial cells shows an increase in the ability of model gut bacteria to adhere to, invade and kill the host epithelium. The pan-sweet taste inhibitor, zinc sulphate, effectively blocked these negative impacts. - Aparna Shil, Havovi Chichger

Gas as a bioweapon?

Typhoid is definately a nasty invader and some beneficial microbes called ‘methanogens’ [yes, they produce methane gas after chowing down that burrito] seem to keep those guys at bay. A study of samples obtained from subjects who had been vaccinated against typhoid, and then challenged with virulent typhoid bacteria showed that those who had higher levels of methanogens, were less likely to become sick from typhoid exposure; there were similar results even with the subjects that had not yet gotten vaccinated.

The researchers theorize that methanogens may help reduce the risk of typhoid by reducing the amount of oxygen in the gut. This could potentially reduce the ability of typhoid to thrive.

"There are so many questions that this initial set of findings raises. This is step one in a 100-step journey," - Claire Fraser PhD

---

REFERENCES

Amon P. Arch Dis Child Educ Pract Ed 2017;102:258–261. http://dx.doi.org/10.1136/archdischild-2016-311643

Ganz, T. Iron and infection. Int J Hematol 107, 7–15 (2018). https://doi.org/10.1007/s12185-017-2366-2

Graef FA, et al. (2021) Fasting increases microbiome-based colonization resistance and reduces host inflammatory responses during an enteric bacterial infection. PLoS Pathog 17(8): e1009719. doi.org/10.1371/journal.ppat.1009719

Aparna Shil, Havovi Chichger, Artificial Sweeteners Negatively Regulate Pathogenic Characteristics of Two Model Gut Bacteria, E. coli and E. faecalis, International Journal of Molecular Sciences (2021). DOI: 10.3390/ijms22105228

Some gut bacteria may protect against intestinal infection https://medicalxpress.com/news/2018-05-gut-bacteria-intestinal-infection.html

Salmonella infection is a battle between good and bad bacteria in the gut https://medicalxpress.com/news/2013-06-salmonella-infection-good-bad-bacteria.html

BL Deatherage Kaiser, et al. A Multi-Omic View of Host-Pathogen-Commensal Interplay in Salmonella-Mediated Intestinal Infection, PLOS ONE June 26, 2013, doi: 10.1371/journal.pone.0067155

---

Please subscribe to my free newsletter by clicking the button. Many future stories will be exclusive to only paid subscribers to BioMedWorks Newsletter: the PREMIUM CONTENT. I would be grateful if you do go on to upgrade to the paid subscription for just $5 a month or $50 a year.