Can Caged Microbes Help Your Kidneys?

A bacterial cage you can swallow processes waste like a miniature kidney.

Posted Jul 06, 2020

No matter what you do, even quietly reading this article, your body is metabolizing. That just means it’s doing its job, keeping the heart beating, the lungs pumping, and the gut gurgling. In the process, it uses up nutrients and churns out waste products, the effluvia of life. Like garbage on a city street, it must be taken out lest the streets get clogged. That job is done by the kidneys, which filter waste from the blood and then excrete it. With damaged kidneys, these toxic wastes build up and your organs start to suffer.

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Caged bacteria help kidneys do their job.
Source: Wildpixel/iStock

What’s the bacterial connection?

We each have some three pounds of bacteria in our gut, protecting us from pathogens and helping us digest our food. A smooth-acting microbiota balances the needs of thousands of species of bacteria, fungi, and viruses jostling around in the warmth of the gut. Many researchers consider this batch of microbes to be like an organ in itself: it consumes nutrients and pumps out a wide range of hormones and neurotransmitters much like an endocrine organ.

But toxins, pathogens, or antibiotics can wipe out large segments of this ecosystem and pitch it out of balance. That is called dysbiosis, and it can lead to a “leaky gut”. This is a somewhat fraught term because in a sense the gut is always leaky. That’s how nutrients are absorbed. But that gut layer is perilously thin, with cells held together by so-called tight junctions. If these junctions loosen up, toxins and bacteria can sneak through the gut lining and into the bloodstream. From there, the heart readily pumps them to every organ in the body.

No matter how beneficial a microbe is in the gut, they are not welcome in the bloodstream. Your immune system quickly tracks them down and kills them. But if that becomes habitual, your entire immune system can go on high alert. There can be a lot of collateral damage as the immune system indelicately hunts down the microbial interlopers. That systemic inflammation can lead to diabetes, heart disease, and kidney disease, among others. The list of diseases that can be triggered by chronic systemic inflammation is long and sobering.

When kidneys go bad

Most kidney patients end up on dialysis, which mechanically filters the toxic waste from the bloodstream. Although traditional hemodialysis depends on directly filtering waste from the blood, another type, called peritoneal dialysis, depends on the leakiness of the gut lining to pull waste from the tissues surrounding the intestines (the peritoneum). Peritoneal dialysis has advantages over hemodialysis and is more convenient, but still requires invasive treatment and diligence.

Kidney patients are often depressed, and some of that is likely attributable to toxic buildup and the tedium of dialysis. But some of that depression may be due to the dysbiosis that led to the kidney disease in the first place. That is the psychobiotic effect: microbes can affect mood.

Bacteria to the rescue

It is good news that researchers have created a probiotic that can help to sweep out some of the garbage and give the failing kidneys a break. Dr. Xian-Zheng Zhang and his colleagues at Wuhan University found two bacterial species that could break down nitrogen-containing waste chemicals like urea and creatinine. When they put them together, the duo could quickly metabolize the waste.

Unfortunately, they produced ammonia in the process, and that can be just as bad as the waste itself, so they added a third microbe that metabolized ammonia. Unfortunately, when they put this trio into a mouse, the bacteria separated into three different locations, and could no longer work together.

To prevent this, they trapped the bacteria into tiny spherical cages, forcing them to partner. Then they coated these with something called a poly-dopamine film that kept large molecules out and only let the small waste particles in. They call it a bacterial micro-ecosystem (BME).

This solution can only take out the garbage in the intestines. How does that lower the detritus in the blood? In an email, Dr. Zhang said it all comes back to the leaky gut phenomenon: “The intestinal mucosa itself is semi-permeable, and nitrogenous waste in the blood can freely enter our digestive system. Furthermore, in the pathological state, the permeability of the intestine will further increase. In fact, peritoneal dialysis also uses the semi-permeability of the peritoneum to remove nitrogenous waste from the blood. The intestinal mucosa is the largest mucosa in humans, and its surface area is about 115 times that of the peritoneum. Therefore, it is possible to use the semi-permeability of intestinal mucosa to remove small molecular wastes in the blood.”

Thus, this oral probiotic acts as a miniature kidney, sweeping up the same detritus that the kidneys do and giving them a welcome break. Dr. Zhang points out that this technique avoids the controversial use of genetic modification. By sequestering these workhorse bacteria in a polymer matrix, he is able to effectively create a new, carefully designed ecosystem that acts like a superorganism. And, because they are contained in a cage, they can’t cross into the bloodstream.

This is just a start. Dr. Zhang says, “nitrogenous wastes generated during kidney failure include not only urea and creatinine but also molecules such as trimethylamine oxide and indole derivatives. Types of compounds that can be degraded by this artificial system need to be further expanded to improve [its utility].” Kidney disease may start from a microbial imbalance, but it also may be alleviated by microbes. That may be ironic, but it is surely welcome.

References

Dinan, Timothy G., Catherine Stanton, and John F. Cryan. “Psychobiotics: A Novel Class of Psychotropic.” Biological Psychiatry 74, no. 10 (November 15, 2013): 720–26.

Zheng, Di-Wei, Pei Pan, Ke-Wei Chen, Jin-Xuan Fan, Chu-Xin Li, Han Cheng, and Xian-Zheng Zhang. “An Orally Delivered Microbial Cocktail for the Removal of Nitrogenous Metabolic Waste in Animal Models of Kidney Failure.” Nature Biomedical Engineering, July 6, 2020, 1–10.

Chen, Yuan-Yuan, Dan-Qian Chen, Lin Chen, Jing-Ru Liu, Nosratola D. Vaziri, Yan Guo, and Ying-Yong Zhao. “Microbiome–Metabolome Reveals the Contribution of Gut–Kidney Axis on Kidney Disease.” Journal of Translational Medicine 17, no. 1 (January 3, 2019): 5.