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. 

Clinical trial suggests dysbiosis may be involved in the progression of acute pancreatitis

The pancreas.  1: Head of pancreas 2: Uncinate process of pancreas 3: Pancreatic notch 4: Body of pancreas 5: Anterior surface of pancreas 6: Inferior surface of pancreas 7: Superior margin of pancreas 8: Anterior margin of pancreas 9: Inferior margin of pancreas 10: Omental tuber 11: Tail of pancreas 12: Duodenum

Acute pancreatitis is a sudden and severe inflammation of the pancreas.  It is responsible for many emergency room visits each year, but what causes its onset is unknown.  Most cases are mild, and can be treated with very passive measures, such as fasting or rehydration.  Other cases though (around 25%), are more severe, and require medical interventions, such as surgery.  Recently, researchers in China conducted a clinical trial on people with acute pancreatitis in order to figure out what, if any, connections existed between the microbiome this disease.  They published their results in the journal Pancreas.

The researchers sampled the feces and blood of 76 patients with acute pancreatitis every few days as the disease progressed (44 were severe cases and 32 were mild), along with 32 healthy controls.  They discovered a dramatic decrease in microbiome diversity occurred in those people with pancreatitis, which was characterized by an increase in Enterococcus and a decrease in bifidobacteria compared to controls.  In addition, pro-inflammatory molecules in the blood were directly correlated with the abundance of Enterococcus in these patients.

It is difficult to connect the microbiome to many inflammatory diseases because the mechanisms for how this occurs are still not totally understood.  Hence, many studies, like this one, are only able to show a correlation between the microbiome and these diseases.  Still though, these correlations can be powerful, and at the very least show the need for more research.  So while it may not be true that a dysbiosis causes acute pancreatitis, they are clearly associated.  

Americans swap foods with Africans and their microbiomes follow – fiber, fat and cancer risk

Phuto pap and porridge, a traditional South African, high fiber, meal.

Despite having similar genetic backgrounds, African Americans are thirteen times more likely to develop colon cancer than rural South Africans.  Indeed, environmental factors, rather than genetics, are thought to be the major factor in developing colon cancer, because recent immigrants’ children’s risk is more similar to where they are living than to their parents’ homeland.  This environmental risk could be primarily caused by a number of factors, such as antibiotic use or drug use, but many scientists believe that diet, and its influence on the microbiome, is primarily responsible.  As it turns out, rural Africans eat much more fiber (almost 5x more) and much less fat (almost 3x less) than African Americans, and these differences have drastic effects on the microbiomes of their hosts.  Not only are the most abundant bacterial species different, but the major metabolites vary greatly as well.  Scientists from the University of Pittsburgh came up with the clever idea of swapping the foods of rural South Africans and African Americans, to investigate how this dietary intervention would affect each group’s microbiomes and risk for colon cancer.  They published the results of their study in Nature Communications last week.

The researchers studied 20 middle aged African American men and 20 middle aged rural South African men.  They each had their microbiomes and colons studied for two weeks while eating their normal diets, and then again for two weeks after swapping diets.  Initially, the Americans had microbiomes dominated by Bacteroides and the Africans by Prevotella.  After the diet though, they noticed a rapid shift in these populations, and it corresponded to an increase in colonic inflammation for the Africans and decrease in the Americans.  In addition, an increase in butyrate, the short chained fatty acid (SCFA) that is thought to be beneficial to health, followed the fiber diet as well, and a decrease was associated with eating the high fat diet; this makes sense, as butyrate is produced as a metabolite of fiber fermentation by the microbiome.  Interestingly, prior to the diet change a top-level analysis of all the metabolic end products of the microbiome showed that Africans produced more of every single one studied except for choline, which is related to heart disease.  Many of the metabolites studied, including choline, followed their diet switch, and were produced according to the food eaten, rather than the person eating it.  Perhaps most importantly, secondary bile acids, which are produced by the microbiome and may be carcinogenic and an important cause of colon cancer, followed the diet as well.  Africans, who produced much fewer secondary bile acids than Americans while consuming their regular diet, had a 400% increase in production after the diet switch, and vice versa for the Americans, who had a 70% decrease.

This study really illustrates the importance of diet on the output of the microbiome.  These metabolites can directly influence our health, and may be more important to our well-being than the bacteria that produce them.  According to this study, it appears that eating more veggies and less fat, something that parents have been saying for a long time, fits in with our understanding of the microbiome.  As Erica Sonnenburg said in our podcast 3 weeks ago, “Feed your microbiome at every meal!”

Episode 6 of The Microbiome Podcast: The microbiome, autism, and serotonin production with Dr. Elaine Hsiao

The sixth episode of The Microbiome Podcast is now available. We had a great chat with Dr. Elaine Hsiao, a new professor at California Institute of Technology. Elaine was the first author on the seminal paper from 2013 that showed a connection in mice of the microbiome and autism spectrum disorder related behaviors. We talked with her about that work as well as more recent work that she published from her own laboratory describing the microbiome’s role in regulating serotonin production.

Listen to the podcast here on our website. Here on iTunes. And here on Stitcher. 

Below are more detailed show notes:

• (2:20) Last week’s guests Erica and Justin Sonnenburg were featured in a New York Magazine article. Read the article. 
• (3:48) The Gates Foundation’s Grand Challenges in Global Health launched a grand challenge titled Addressing Newborn and Infant Gut Health Through Bacteriophage-Mediated Microbiome Engineering. Learn more. 
• (6:22) uBiome launched a clinical laboratory. Read more. 
• (7:56) Second Genome partnered with the University of Cork in Ireland to develop therapies for inflammatory bowel diseases. Read more.
• (9:02) Dupont recently acquired Taxon Biosciences, a microbiome company. Read more. 
• (11:15) A caller asked how long his microbiome would take to recover to it’s previous state after taking antibiotics. We based the answer on a paper by David Relman published in 2010. Read the paper.
• (16:19) We start the interview with Elaine Hsiao. Check out her laboratory webpage.
• (18:00) We talked with Elaine about her seminal paper on the microbiome and it’s possible connection to autism spectrum disorders. Read the paper.
• (31:06) We talked with Elaine about her recent paper showing that gut bacteria are important for production of serotonin. Read the paper.

We will be back in two weeks with Drs. Eugene Chang and Vanessa Leone from the University of Chicago discussing how the microbiome may be involved in the complex relationship between disruptions to circadian rhythms and obesity. Please call in with any questions for Bill and David or for Drs. Chang and Leone to 518-945-8583. 

The fate of the gut microbiome following stem cell transplant

Bone marrow prior to transplant

Hematopoietic stem cell transplant (HSCT) is a difficult procedure that is usually administered to patients suffering from bone marrow or blood cancers such as multiple myeloma or leukemia.  Unfortunately, many patients who receive this treatment develop acute graft-versus-host disease (aGvHD), a multi-organ system immunologic disorder that is particularly detrimental to the gastrointestinal tract. 

In light of increasing evidence highlighting the importance of the symbiosis between the microbiome and human hosts, researchers set out to explore the fate of gut microbiota in pediatric patients who had undergone HSCT.  Specifically, phylogenetic profiles and functional properties were examined in a longitudinal analysis to develop a better understanding of the specific role the gut microbiome plays in patients who develop aGvHD following a HSTC procedure. 

Ten pediatric patients who had undergone HSTC, 5 of which had developed aGvHD, were selected for analysis.  The trajectory of the microbiota ecosystem was monitored using gene pyrosequencing of fecal samples, which were collected before, during, and after the HSTC procedure.  Collection and observation continued for 3 to 4 months.  Additionally, researchers examined short-chain fatty acid (SCFA) production samples in the patients as a measurement of microbiota metabolic activity.  Short-chain fatty acids are critical metabolites that microbiota require in order to maintain healthy physiology.  Healthy microbiota are critical toward educating the immune system and maintaining homeostasis.

Marked changes were observed in the gut microbiome populations of all 10 patients immediately following the HSTC procedure.  There was a massive invasion of new bacterial species following the procedure, with less than 10% of the original microbiota being conserved.  In particular, there was a significant loss in health-promoting bacterial species such as Faecalibacterium and Ruminococcus.  Two months after the procedures, the species richness and metabolic activities in the patients’ guts was restored. 

The patients who developed aGvHD experienced a major drop in health-promoting bacteria and higher abundances of invading bacteria as compared to non-aGvHD patients.  Interestingly, the gut microbiomes of the non- aGvHD patients contained significantly higher populations of Bacteroides phylum.  On top of this, Bacteriodes were the most abundant species observed among the original 10% of microbiota conserved through the HSTC operation. 

This study points to the importance of the gut microbiome in helping maintain healthy integrity of the gut immune system following a HSTC procedure.  The finding that having low Bacteriodes populations may be an unrecognized consequence that could lead to the development of aGvHD is particularly interesting.  Should these bacteria be as important as this data suggests, preventative microbiome-driven therapies could be explored with the aim of preventing post-HSTC procedural aGvHD onset.  A therapy that could maintain healthy Bacteriodes populations prior to HSTC operations could perhaps present a viable solution.  

Fungi associated with enterocolitis for those with Hirschsprung's disease

Plot of the fungal populations in the stool of children without enterocolitis (left), and those with enterocolitis (right).  Notice the substantially larger population of Candida, and Candida albicans in the population with enterocolitis.

Hirschsprung's disease (HD) occurs when an infant is born without ganglion cells in their colon.  The result is that the portion of the colon that lacks these cells cannot relax and pass stool.  It is normally treated surgically by bypassing this portion of the colon with a normally functioning part of the colon.  Unfortunately, around 25% of patients that undergo this procedure eventually get enterocolitis (i.e. colon infection), which can be life threatening. 

Researchers have long believed there to be a bacterial cause for this type of Hirschsprung's associated enterocolitis (HAEC), however the connection has remained elusive.  Researchers, primarily from Cedars-Sinai, published the results of a study this week that suggests fungi, not bacteria, are primarily responsible for causing HAEC.  They published their results in the journal PLoS ONE.

The researchers developed a cohort of seventeen children that suffered from HD as an infant, and who had surgery to correct it.  Eight of these children developed HAEC, while the other nine remained healthy.  The researchers took stool samples from each of the children and measured their bacterial and fungal populations.  Surprisingly to the researchers, there was no statistical difference in the abundance of various bacteria between the two groups.  However, there was a much different story with the fungi.  The normal HD patients had a higher diversity of fungi than the HAEC patients.  In addition, HAEC patients were dominated by Candida species, while the others were not.  Moreover, an average of 90% of the Candida was Candida albicans, a pathogenic fungus that we have written about on the blog in the past.

The scientists were not able to say whether or not Candida albicans was responsible for causing the enterocolitis in these patients, however they do suggest it as a possibility.  To that end, they suggest that perhaps antifungals, rather than antibiotics, should be used to combat HAEC, especially given the fact that antibiotics can lead to ‘blooms’ in fungal species.  We often discuss the importance of all the aspects of the microbiome beyond just the bacteriome (bacteria), such as the virome (viruses), and mycobiome (fungi), and this paper shows another example of why these various ‘omes’ should not be neglected during microbiome research.