The effect of various treatments for juvenile Crohn’s disease on the microbiome

CT scan showing Crohn's disease in the fundus of the stomach

Crohn’s disease is a type of inflammatory bowel disease that is characterized by an autoimmune response in the colon.  It is generally thought that the bacteria in the gut elicit this immune response and cause the disease.  In otherwords, Crohn’s is caused by a shift in the microbiome from a healthy state, to a dysbiotic one, although the ultimate cause of the disease is still unknown.  The standard of care for Crohn’s in adults is combinations of immunosuppressive drugs, although in children this is not normally recommended.  Instead, children take either a prescribed diet, normally something like Soylent that involves only essential nutrients, or antibiotics.  Scientists from UPenn recently monitored the microbiomes of children with Crohn’s that were put on various courses of treatment, as well as the progression of the disease.  They discovered the changes that occurred in the microbiome that yielded a therapeutic response, and many new associations between the microbiome and Crohn’s disease.  They published their results in Cell Host and Microbe.

The scientists measured the microbiomes and inflammatory markers of 90 children before and after entering therapy for Crohn’s: 52 taking anti-TNF (an immunosuppressant), 22 taking the enteral nutrition exclusively (i.e. something like soylent), and 16 taking the enteral nutrition along with any other food they wanted.  The scientists also took samples from 26 healthy children.  They discovered that of the 45 most abundant bacteria in each child, 14 were different between the Crohn’s children and the healthy children.  These included bacteria such as Prevotella and Odoribacter that were largely absent from the Crohn’s group, and Streptococcus, Klebsiella, and Lactobacillus that were in higher abundances in the diseased group.  Overall diversity was also higher in healthy patients compared to those with Crohn’s.  The researchers also discovered that high levels of fungi, such as Saccharomyces cerevisiae, in the stool were high associated with Crohn’s.  When the researchers monitored the response of Crohn’s patients to treatment they saw that in many patients the microbiome shifted rapidly to a healthier state, with less inflammation, within a week of treatment for all three therapies involved.

This study helped further define the dysbiosis that is associated with Crohn’s disease, as well as demonstrate how this dysbiosis is altered using treatment.  It was especially useful that treatment naïve children were used in the study, as many adult studies are unable to remove confounding variables of various previous courses of treatments.  IBD is a difficult disease to study because of its complexity, but this study supports the hypothesis that a dysbiosis is at the root of the problem.

Fungal infection in brain highly associated with Alzheimer’s disease

Common example of fungi hyphae

Alzheimer’s disease is a brain disease in which slow and irreversible neuronal deterioration occurs. It is characterized by the accumulation and aggregation of proteins in the brain and central nervous system (CNS), although no one knows the cause of this protein aggregation, or if these amyloids are even responsible for the neurodegeneration that occurs, rather than just associated with it.  More recently, some scientists believe that Alzheimer’s is a disease caused by inflammation, because sufferers of the disease have high levels of many inflammatory signals in their brains.  Indeed, some infections that would drive inflammation have been found in Alzheimer’s patients, but nothing convincing as of yet.  This week though, scientists from Spain discovered that a fungal infection in the brain is highly associated with the disease.  They published their results in Nature Scientific Reports.

The scientists made histological sections from the brains of 10 patients with Alzheimer’s and 10 healthy controls, and stained them for the presence of fungi.  Remarkably, all 10 of the patients with Alzheimer’s showed signs of various fungi, whereas none of the healthy controls did.  The fungi were seen both intracellularly and extracellularly, meaning that in some cases the fungi actually entered the neurons in the brain.  The fungi included both yeasts, such as Sachromyces cerevisae, as well hyphae forming fungi such as Neosartorya hiratsukae. In addition, the scientists found traces of these fungi in the blood of the Alzheimer’s patients as well, suggesting that they may originate through common pathways, and spread into the brain.

While this study does not in any way prove these fungi are causing the disease, it certainly is compelling data that they are primary culprit for the disease.  As the authors state, if one were to assume that the etiology of the disease is caused by the fungi, all the symptoms of the disease can be explained.  For example, the slow progression and inflammatory nature of the disease.  Fortunately, If the fungi are responsible there could be many possible therapeutic approaches, including antifungals.