The Links between Gut Microbes and Human Disease

BY DEVORAH SAFFERN

Our guts are composed of thousands of bacterial species, many of which are essential for physiological processes like digestion and fighting disease. Recent findings suggest that these microbes – the types of which are specific to each individual – are linked to several diseases that affect much of our population. Studying the gut microbiome may therefore reveal the mechanism or cause of these diseases and help us develop better treatments or prevention methods. Here, we focus on two papers in particular that were published in the past three months and analyzed the links between the gut microbiome and specific diseases: a University of Oregon study connects the gut bacteria to intestinal inflammation; and a California Institute of Technology study examines the gut microbiome in patients with Parkinson’s disease.

The first of these papers, published in PLOS Biology by Rolig et al. this February, describes a zebrafish mutation resembling Hirschsprung disease. The disease is caused by a lack of neural cells that are necessary for the enteric nervous system (ENS), which physiologically regulates sporadic muscle contractions in the stomach. Researchers started by observing mutant fish with these inflamed intestines; they measured the amounts and types of bacteria in their intestines, and found an excess of certain inflammation-causing bacteria. There was also an absence of other bacterial strains typically found in the gut. When they administered anti-inflammatory bacteria (those without links to inflammation) into the intestines no inflammation was observed.

devorah
Bacteria linked to inflammation (right) and random gut bacteria (right) were administered to Zebrafish.

The researchers concluded that ENS regulation of microbes in the intestine is directly connected to inflammation and overall health in the intestine. In other words, bacteria present in the intestine are an essential contributing factor in inflammation and disease symptoms. Given that this disease is quite severe, causing a third of people with the mutation to develop intestinal dysbiosis (also known as Hirschsprung-associated enterocolitis), whose symptoms include bowel disfunctions as well as other serious risks, understanding the link to microbiomes is a significant step toward finding a cure. Additionally, other common diseases such as inflammatory bowel disease, cystic fibrosis, and diabetes may be regulated by similar mechanisms, potentially benefiting as well from an analysis of these links between the gut microbiome and human disease.

The second paper, published in the Cell journal by Sampson et al. in December 2016, sought to explore the potential connections between gut microbes and Parkinson’s disease. Specifically, microbes from human Parkinson’s patients were orally administered to germ free mice and resulted in neuroinflammation and impaired motor abilities. Additionally, mice with an abundance of the protein α-synuclein (αSyn), a protein often resulting in Parkinson’s disease in humans, were administered αSyn taken from human Parkinson’s patients. The researchers found that those who received the protein from Parkinson’s patients experienced worse symptoms than the mice that received bacteria from healthy patients.

The researchers concluded that these specific microbiomes are present in all mice displaying Parkinson’s disease symptoms, and that signals between the brain and gut are an essential component of the disorder. Based on their findings and previous studies, they proposed that neurological conditions in general stem not only from brain abnormalities but also from the gut microbiome.

These are only two of many studies linking gut bacteria to various human diseases. A number of reports demonstrate that a link exists between neurodevelopment and neurological disease. In various instances, the gut’s neuro-transmitting and immune signals, as well as hormones, have been shown to have an effect on the brain. Additionally, common gastro-intestinal microbes have been implicated in a number of diseases, including Parkinson’s, Alzheimer’s, Huntingtons, and many others, suggesting a similar mechanism. Studying the specific mechanisms and connections between gut bacteria and human disease can help us find better treatments for the many people affected by these diseases. We therefore need to perform more experiments testing bacterial mutations and illnesses to find the root causes of the symptoms. While there is still much to be analyzed, these studies demonstrate the potential in linking gut microbiomes to disease, giving hope for better cures and prevention methods.

Image source: Rolig AS, Mittge EK, Ganz J, Troll JV, Melancon E, Wiles TJ, et al. (2017) The enteric nervous system promotes intestinal health by constraining microbiota composition. PLoS Biol 15(2): e2000689. doi:10.1371/journal.pbio.2000689

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