proteobacter

The gut microbiome shift during pregnancy is related to the mother’s secretor status

Fucose chemical structure

Fucose chemical structure

An estimated 20% of women of European descent are not able to produce mucous that have fucose sugars attached to the ends of their mucin molecules.  These women are called ‘non-secretors’, as opposed to ‘secretors’ who can fucosylate their mucins.  This rather peculiar genetic anomaly is not appreciated until it is looked at under the lens of the microbiome.  Many of the microbiota in the gut feed off the host’s mucins for energy, and the lack of fucose is a major factor in dictating which communities can survive in their guts.  During pregnancy the mother’s gut microbiota undergoes a dramatic shift, although what variables are important in determining this shift remain unknown.  Last week though, researchers from Finland showed that secretor status was an important indicator in how a women’s gut microbiome shifts during pregnancy.  They published their results in PLoS ONE.

The researchers sampled the gut microbiome of 71 women throughout their pregnancy, and compared it to the secretor status, as determined by genetic testing.  In the first trimester of pregnancy each women, secretors and non-secretors alike, had similar diversities in their gut microbiota.  However, by the third trimester the non-secretor’s gut microbiomes were much lower than their secretor counterparts.  When the scientists measured specific phyla, they observed an increase in the abundance of Actinobacteria in the secreting women, and an increase In the abundance of Proteobacter in the non-secretors.

The changes in gut microbiota in these women may be very important to the microbiome of the infant that is born to them.  As an infant passes through the birth canal he or she is exposed to the mothers’ vaginal and gut microbiota, and these bacteria serve as the initial populations that seed the infants’ own guts.  In addition, some of these specific bacterial populations, such as Proteobacter, are implicated in diseases like IBD.  If these bacteria persist in the mother after birth they may explain the onset or increased risk of some of these diseases.

Please email blog@MicrobiomeInstitute.org for any comments, news, or ideas for new blog posts.

The views expressed in the blog are solely those of the author of the blog and not necessarily the American Microbiome Institute or any of our scientists, sponsors, donors, or affiliates.

The microbiome’s role in pediatric intestinal failure and associated liver disease

Gray's anatomy schematic of the liver.

Gray's anatomy schematic of the liver.

On Wednesday we talked about children who suffer from short bowel syndrome (SBS), specifically highlighting the role of the gut microbiome alongside its relationship to parenteral nutrition (PN).  In addition to demonstrating microbial dysbiosis in children with SBS, intestinal dysbiosis was noticed in patients receiving PN, while those who had been weaned off showed bacterial overgrowth. 

SBS can also lead to intestinal failure (IF) and further complications.  Among the many, PN and disrupted bowel function have both been shown to lead to IF-associated liver disease (IFALD), which can result in severe illness and even death.  Steatosis, a pathological indication used to describe abnormal lipid retention in cells, has been observed in liver histological samples. 

The cause of IFALD remains unclear, but findings from studying other liver disorders suggest involvement of the gut microbiome.  Intestinal overgrowth has been postulated for quite some time now, but evidence is lacking and the exact biological underpinnings that lead to liver injury remain unclear.  Researchers in Finland sought to address this, estimating that IF-induced disruptions to the gut microbiome of pediatric patients played a direct role in causing this liver damage. 

Twenty-three pediatric patients developing IF were selected for this study.  Researchers collected fecal samples to analyze microbiota populations and took liver biopsies to examine inflammatory damage and fibrotic tissue morphology.  In line with previous findings, the microbiomes of patients with IF had limited bacterial diversity and species richness as compared to those of healthy children and adults. 

A strong correlation was observed between microbiota composition and liver steatosis, and different microbiota strains were shown to be associated with different stages of the disease progression.  Additionally, an overabundance of microbiota in the Proteobacteria phylum was observed in patients undergoing PN.  The Proteobacteria phylum contains many opportunistic pathogenic bacteria, including E. coli.  Interestingly, Proteobacteria species produce lipopolysaccharides, which are known toxins to the liver.  The researchers were also able to model that bacterial composition was a strong predictor of liver steatosis than nutrition history or bowel length post-resection surgery. 

These findings led the researchers to propose that intestinal resection, alongside PN, disrupts the intestines, and consequently native microbiota populations.  The disruption and species decline invites opportunistic bacteria, such as those in the Proteobacteria phylum, to populate the intestine.  These bacteria release of lipopolysaccharides into the blood stream, and upon reaching the liver, induce inflammatory toxic damage leading to steatosis. 

This study complements Wednesday’s discussion and helps us makes better sense of a convoluted disease complication that has drastic consequences.  Understanding the microbiome’s influence on post-SBS liver disease can help clinicians make informed decisions to rescue pediatric patients from these ailments.  

Please email blog@MicrobiomeInstitute.org for any comments, news, or ideas for new blog posts.

The views expressed in the blog are solely those of the author of the blog and not necessarily the American Microbiome Institute or any of our scientists, sponsors, donors, or affiliates.

New info on fecal microbiota transplants for C. difficile and ulcerative colitis

"Fecal bacterial communities of recurrent [ C. diff ]  patients shift towards [healthy] fecal bacterial communities after FMT.   Pre-FMT patient samples (red circle); post-FMT patient samples (green circles); trajectory of patient fecal communities after FMT (blue line)."   Image and caption from the   C. diff   paper:  Weingarden  et al.   Microbiome   2015   3  :10   doi:10.1186/s40168-015-0070-0

"Fecal bacterial communities of recurrent [C. diff]  patients shift towards [healthy] fecal bacterial communities after FMT. Pre-FMT patient samples (red circle); post-FMT patient samples (green circles); trajectory of patient fecal communities after FMT (blue line)."
Image and caption from the C. diff paper: Weingarden et al. Microbiome 2015 3:10   doi:10.1186/s40168-015-0070-0

Two important papers regarding fecal microbiota transplants (FMTs) were published last week.  The first was an examination of a patient’s microbiome over time after he or she undergoes an FMT to treat C. difficile.  The second showed the results of clinical trials that used FMTs in an attempt to treat ulcerative colitis.   The FMT papers, which are described below, improve our understanding of this procedure, which holds promise to treat various microbiome-based diseases.

The C. diff paper, published in the journal Microbiome, attempted to answer the question: Do the microbiome changes that occur after FMT remain long after the procedure?  We know that FMTs are highly effective in treating C. diff because they install a healthy microbiome that can crowd out the infection.  However, it is unknown if these new bugs that take hold are transient, or if they become permanent members of the gut.  The researchers sampled the microbiomes of FMT donors and recipient patients before and up to 84 days after an FMT procedure to treat C. diff.  They discovered that the recipients’ dysbiotic microbiomes stabilized quickly, and after just one day they closely resembled the donors’ microbiomes.  Continued measurements showed that the microbiomes deviated over the next few weeks, but that they remained healthy.

The colitis clinical trial, published in the journal Gastroenterology, attempted to discover if FMTs could treat ulcerative colitis.  Ulcerative colitis is widely considered to somehow be related to a dysbiosis in the microbiome, so can FMTs from healthy donors treat this disease?  The study was a double blind randomized clinical in which 48 people suffering from ulcerative colitis either received stool from healthy donors (treatment) or just an FMT of their own stool (control).  7/23 patients who received stool from a healthy donor were in remission after 12 weeks, while 5/25 patients who received their own stool were in remission at that time.  Unfortunately, this is not a clinically significant result based on the number of patients involved.  The researchers measured the bacterial abundance in all of the patients microbiomes before and after treatment.  Before treatment the microbiomes all had some baseline similarity.  After treatment, though, the patients who responded to treatment from a healthy donor all had an increase in certain Clostridia, and the patients who responded to treatment from their own stool all had in increase in certain Bacilli, Proteobacteria and Bacteriodetes.  The researchers feel that this information warrants further study.

FMTs are an exciting new therapy that may be important in treating some really nasty diseases.  We do want to remind people, though, that it is still an unproven technique that should only be performed under the guidance of a doctor.  As we have written about before, the promise of the microbiome is what makes FMTs both attractive, but potentially dangerous at the same time.

Please email blog@MicrobiomeInstitute.org for any comments, news, or ideas for new blog posts.

The views expressed in the blog are solely those of the author of the blog and not necessarily the American Microbiome Institute or any of our scientists, sponsors, donors, or affiliates.

Emulsifiers in food cause many adverse health effects in mice

Emulsifiers are often used in ice cream to keep it stable and to give it it's texture.

Emulsifiers are often used in ice cream to keep it stable and to give it it's texture.

People often have spirited and impassioned views on the safety and consequences of adding ‘unnatural’ molecules to food.  An important aspect of this debate that everyone must keep in mind is the impossibility of testing every component of every molecule for its safety and long term impacts.  That being said, it should come as no surprise that new research can often teach us about the unexpected and overlooked safety issues regarding many food additives.  The newest class of compounds to come under scrutiny is emulsifiers, and a new paper published in Nature last week shows that these compounds may negatively impact the body through modulation of the intestinal lining and the microbiome. 

Emulsifiers are compounds that increase the stability of an emulsion.  They are often molecules like surfactants that have two parts, hydrophobic carbon chains and hydrophilic polar head groups.  Soap and egg yolks are common examples of emulsifiers.  There  are, of course, chemically produced emulsifiers as well that are often used in food.  Two examples of these, which were the emulsifying compounds used in the study, are polysorbate-80 (P80) and carboxymethylcellulose (CMC), and they are added to all sorts of foods like ice cream and pudding.  Evidence from this paper suggests though, that at least in mice these emulsifiers are wreaking havoc on the gut and microbiome.

A team of researchers from Israel, Cornell, and Emory did a variety of experiments on mice that were fed either of these emulsifiers in their water (at a concentration of 1%, similar to the levels added to human food.)  They first noticed that these mice had greatly compromised mucous layers on their gut, which allowed for bacteria to actually reach and be in contact with their epithelial gut cells.  In these mice gut permeability (leaky gut), inflammation, and incidences of colitis were all increased.  In addition, the inflammatory response and gut permeability were directly related to the average distance of bacteria to the actual epithelial layer; the closer the bacteria the more inflammation and permeability.

The researchers also measured the microbial populations of the feces in these mice and those that were eating emulsifiers had much less diverse microbiomes, which were enriched in Proteobacter, which are known to be associated with inflamed guts, and reduced in Bacteroidales, which are associated with healthy guts.  Also those eating emulsifiers had in increase in Ruminococcus gnavus which is associated with type 1 diabetes, as we have written about in the past. Interestingly, those mice that were given the emulsifiers tended to eat a lot more food than there control counterparts, and this led to weight gain and obesity amongst the mice drinking emulsifiers.  Moreover, these same mice had higher fasting glucose levels, indicative of impaired glycemic control and metabolic syndrome.  The scientists tested if these effects were seen in mice that were fed the emulsifiers in their food, rather than in their water, and the same outcomes were observed.  In addition, the scientists observed shifts in the production of certain short chained fatty acids and bile acids produced by the microbiome in mice fed emulsifiers (click on the tags below to read about the wide range of health effects that both these compounds have been implicated with).

The researchers then did a series of experiments that showed that it was the actual shifts in the microbiome populations and not just the change in mucous that was primarily responsible for the adverse health effects in the mice given emulsifiers.  For example, germ free mice that were given  emulsifiers did not have compromised mucous, and many of the negative health effects like inflammation were not observed.  On the other hand, performing a microbiome transplant from a mouse given the emulsifiers to a mouse that was not given the emulsifiers did result in these negative health effects, including the bacterial penetration of mucous to the epithelial lining.

This was a fantastic article that may, in time, prove to be immensely important.  Of course all the usual caveats apply, such as studies in mice are not indicative of human responses, and more studies must be performed in order to confirm these findings.  Still though, the introduction of emulsifiers into the mice’s diets resulted in many of the negative health impacts that are associated with the microbiome, something that we really haven’t seen in the literature before now.

Please email blog@MicrobiomeInstitute.org for any comments, news, or ideas for new blog posts.

The views expressed in the blog are solely those of the author of the blog and not necessarily the American Microbiome Institute or any of our scientists, sponsors, donors, or affiliates.

Asthma, COPD, and the Microbiome

Asthma and chronic obstructive pulmonary disease (COPD) are both illnesses that are caused by chronic inflammation of the respiratory tract, and recent research suggests that the microbiota of the lower respiratory tract may influence the development of these two diseases.  The upper respiratory tract, though, remained unstudied, until a new article was recently published in PLoS ONE.  This article characterized the microbiome of the oropharynx (in the upper respiratory tract) to discover the association between these problems and the microbiome.

Samples were swabbed from the oropharynx of patients who were recently diagnosed with asthma and COPD, as well as from a healthy control group.  Researchers performed 16S rRNA gene sequencing of the bacteria collected from the patients, in order to determine which bacteria were present. They found that there are few differences in microbiome diversity between asthma and COPD patients, however there was a prevalent presence of the bacteria Lactobacillus (phylum Firmicutes) and Pseudomonas (phylum Proteobacteria) in both, which were identified in only very small amounts in healthy patients. On the contrary, the upper respiratory tract of healthy individuals was found to be dominated by Streptococcus, Veillonella, Prevotella, and Neisseria, from the phylum Bacteroidetes, compared to individuals with asthma and COPD.

This study showed distinct differences in the microbiomes of diseased and healthy individuals.  The researchers also note that the low abundance of Neisseria they observed in this study has also been seen in studies of smokers, meaning that this bacteria may be important to respiratory health.  Further work is still needed, though, to determine if the bacteria identified in this study are contributing to the diseased individuals.  Even if they are not, they could still potentially be used in diagnosis. 

Please email blog@MicrobiomeInstitute.org for any comments, news, or ideas for new blog posts.

The views expressed in the blog are solely those of the author of the blog and not necessarily the American Microbiome Institute or any of our scientists, sponsors, donors, or affiliates.

Hospitals influence infants' intestinal microbiomes

Pig Ileum with and without NEC.  Figure taken from different study.

Pig Ileum with and without NEC.  Figure taken from different study.

As we have previously discussed, necrotizing enterocolitis (NEC) is a bacterial infection that often occurs in low weight, premature infants, that can lead to death.  The rates of NEC vary between neonatal intensive care units (NICUs), meaning that individual NICUs may play a role in causing NEC.  A new study published in the journal Microbiome sought to discover if different NICUs had any influence on a premature infants' gut microbiome.

Around 60 preterm babies had their microbiome studied during their first week of life.  Two hospitals were chosen for the study, one in Cincinnati, Ohio, the other in Birmingham, Alabama, over the course of two years.  The researchers discovered that while many of the infants' microbiomes showed similar characteristics, such as an abundance of Proteobacteria, there were nevertheless statistically significant differences in the microbiomes between hospitals, and temporally within hospitals.  For example, one hospital's infants had a higher level of Firmicutes than the other hospital.  

Understanding the risk factors for NEC will ultimately help prevent the disease, so while this study does not show any direct association between hospital and NEC, it shows the need for a large scale epidemiological study that spans many geographic areas over long periods of time.  

Please email blog@MicrobiomeInstitute.org for any comments, news, or ideas for new blog posts.

The views expressed in the blog are solely those of the author of the blog and not necessarily the American Microbiome Institute or any of our scientists, sponsors, donors, or affiliates.