Gut dysbiosis in anorexia nervosa patients

Anorexia nervosa (AN) is a devastating eating disorder in which a patient severely restricts food intake and may have purging behaviors. AN of course results in physical harm but there are also very significant psychosocial effects because of the disease. Studies have shown that the gut microbiome plays an important role in weight gain and it is therefore reasonable to believe that gut dysbiosis could be seen in individuals with anorexia nervosa.

Scientists in Japan characterized the microbiome of AN patients and compared them to healthy controls. They studied 25 women with AN and compared their microbiomes to 21 age-matched healthy females. They found that AN patients had a lower amount of total bacteria and specifically, lower amounts of C. coccoides group, C. leptum subgroup, B. fragilis, and Streptococcus.  

Several papers have shown the importance of gut bacteria on weight gain including those showing the impact that antibiotic use in poultry has on creating larger chickens. Other studies include those linking obesity to specific gut bacteria as well as studies that show transplantation of bacteria, specifically Christensenella minuta, reduced weight gain in mice.

These studies comprehensively show that there is some connection between gut bacteria and weight gain and therefore investigating it as a therapeutic mode for anorexia nervosa is logical. While this study was small in scale and no causal links can be made, it is important to understand that gut bacteria differs between AN patients and healthy controls. Microbiome therapies may be an option for treating anorexia nervosa.

The gut microbiome may contribute to susceptibility to developing alcoholic liver disease

Alcoholic liver disease (ALD) is a major public health issue, yet the underlying mechanisms between ethanol consumption and injury to the liver are poorly understood.  Alcoholics vary in their susceptibility to developing ALD and alcoholic hepatitis (AH) despite consuming similar amounts of alcohol.  Taken together, this evidence suggests that other factors contribute to the onset and progression of ALD other than direct toxicity of alcohol.  Intestinal inflammation and pro-inflammatory bacterial products have also been observed in ALD patients and preclinical mice models, and intestinal dysbiosis has been observed in patients with alcohol dependency.  With this in mind, a team of European researchers devised a strategy to demonstrate microbiome dysbiosis as a casual driver of liver injury. 

The researchers transplanted human gut microbiota into germ-free mice, and the mice were then placed on a high-alcohol diet.  Microbiota were harvested from human alcoholic patients with or without AH (or low severity AH).  Mice transplanted with AH-microbiota had marked increases in symptoms of liver disease as compared to those mice that received microbiota transplants from non-AH alcoholic patients.  These include severe liver inflammation (including increases in T lymphocytes and natural killer cells), more necrosis in the liver, and higher intestinal permeability.  Enterobacteria counts were high in sever-AH patients and faecalibacterium genus was associated with AH-microbiota with low severity.  In an interesting spin, the researchers also transferred microbiota from an alcoholic patient without AH to mice with liver lesions.  Interestingly, mice who had received these microbiota displayed a reduction in serum alanine aminotransferase levels and a decrease in liver regeneration, suggesting that these microbiota could even possibly reverse alcohol-induced liver lesions. 

These findings not only support an association between the gut microbiome and susceptibility to developing alcoholic liver disease, but also provide evidence that these bacteria may drive disease onset.  These were important findings that support microbiota-causal effect rather than dysbiosis as a consequence of liver disease.  This data could perhaps promote development of novel diagnostic techniques that assess the gut microbiome or bacterial metabolites of alcoholic patients.  Methods such as manipulating the microbiome as a therapeutic approach for these patients could also be explored. 

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.

Microbiome of rheumatoid arthritis patients is altered and partially restored after treatment

A recent study found that the oral and gut microbiome were altered in patients with rheumatoid arthritis (RA). RA is an inflammatory disease that generally affects the joints in one’s hand and feet and can eventually cause bone erosion and deformity. RA occurs when a person’s immune system attacks it’s own tissues and can be implicated in other parts of the body as well.

In the study published in Nature Medicine, the scientists sequenced fecal samples of 212 individuals. This 212 sample included 77 people with RA not undergoing treatment, 80 healthy participants unrelated to people in the study,17 RA patients as well as17 healthy relatives to match the 17 RA patients and finally, 21 patients with RA undergoing treatment with disease-modifying anti-rheumatic drugs (DMARDs). They also took dental and saliva samples from individuals with and without RA.

They found that the bacterial composition of RA patients differed from patients without RA however the patients undergoing DMARDs had microbiomes that more closely resembled the healthy control subjects. This was important because it provides support to the theory that RA is a disease that may be brought about or affected by pathogenic bacteria or a lack of other specific bacteria.

This result may be a step forward toward the development of therapeutics targeting the microbiome of individuals of RA. It also may be possible to better diagnose or even determine the prognosis of RA patients by studying their microbiome. Further work will be needed with larger patient populations but this is a positive development for treating and studying RA using the microbiome. 

Cigarette smoke changes the gut microbiome

When we talk about smoking cigarettes, we usually discuss the harmful effects that it has on our lungs, mouth, skin, and other parts of the body. However, we don't often talk about the gut even though cigarette smoke is the best-known environmental risk factor for Inflammatory bowel diseases (IBD), Crohn’s disease and ulcerative colitis.  While the exact mechanism for why people get these diseases is not yet known, it is recognized that a dysbiosis of the gut plays a contributing role to the onset of these conditions. A research team in Germany investigated the effects that cigarette smoke exposure had on the mucus layer and the microbes in the gut.

The scientists exposed mice to cigarette smoke or air for a period of 24 weeks. They found there was a shift in the microbial community in the caecum and distal colon after exposure to smoke. Specifically, there was an increase in Lachnospiraceae in the colon however it remained the same in the ileum, the last part of the small intestine.

They also found that smoke exposure led to changes in mucin exposure. Mucin is a type of protein that is known for producing gels that act to lubricate and protect parts of the body, both internal and external. The most common mucins are Muc2, Muc3, and Muc4. Muc2 for example is a protein that is secreted onto the mucosal surfaces of the large intestine and serves as a protective barrier for the epithelium. In this study, they found that Muc2, Muc3, and Muc4 gene expression was altered after cigarette smoke exposure.

The authors hypothesize that cigarette smoke affects the immune system in the ileum and may lead to the inflammation associated with Crohn’s disease. Overall, this study found that exposure to cigarette smoke had a profound effect on the gut bacteria and mucin composition in the mouse. While this was not done in humans, the same effects would likely be seen.

Saliva may be able to predict severity of cirrhosis

Cirrhosis is a disease of the liver in which healthy liver tissue is replaced with scar tissue, preventing the liver from properly functioning. Scientists at Virginia Commonwealth University found that changes in the microbiome of saliva were found in cirrhosis patients in comparison to individuals without the disease.

The scientists analyzed the bacterial contents of both stool samples and salivary samples from patients with varying degrees of cirrhosis as well as healthy controls.  Previous studies had shown that cirrhosis patients had altered fecal microbiomes and in this study, they found that patients also had altered salivary microbiomes. 102 individuals with cirrhosis were studied including 43 of them who previously had hepatic encephalopathy (HE), a severe result of liver disease that results in confusion, coma, and can even lead to death.

Patients who previously had HE saw a decrease in bacteria in their saliva that were normally in the body and an increase in bacteria that were pathogenic, including Enterobacteriaceae and Enterococcaceae, Similar results were found in their stool samples. Of the 102 patients, 38 of them were hospitalized within 90 days of the study.  Those 38 individuals had greater salivary dysbiosis than those who were not hospitalized.

They also looked at an additional 43 individuals without cirrhosis and 43 with cirrhosis and looked at the inflammatory profile in the saliva. They found that the cirrhosis patients had immune deficiencies that were similar to that in the gut.

This study showed that the salivary microbiome was similar to the fecal microbiome in patients with cirrhosis. This provides evidence that you may be able to use saliva to predict the disease severity of patients with the disease as well as providing a tool for testing treatment options for patients with the disease.