Hospitals influence infants' intestinal microbiomes

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.  

Altering the microbiome, diet, probiotics, and FMT

I recently had the pleasure of hearing a lecture by Eric Alm, an associate professor at MIT.  During the lecture he described a number of studies his group has performed, and I would like to share some of his conclusions.

In his first study he and his student sampled their own microbiome every day over the course of one year, while cataloging every minute detail of their lives over the same time frame.  They were investigating what activities have real effects on the microbiome, and as they discovered, unsurprisingly, what one eats is the most important.  They found that the amount of fiber in the diet perturbed the microbiome most, in addition to things like orange juice, yogurt, fruits, and soup.  They also discovered that after flossing, a certain bacteria from their mouth, would show up in their stool.  More importantly, they confirmed that the microbiome is robust, and rebounds after drastic changes like vacationing in foreign countries.  In addition, they learned that perturbations occur within 24 hours.  Most of the results of the study can be found here.

In another study, Eric discovered that the microbiome is a hotbed for horizontal gene transfer.  With so many genetically different bacteria living and evolving in close quarters there has been a great amount of genes passed around.  He also discovered that the microbiome of farm animals (which are given antibiotics to gain weight), develop antibiotic resistance, which is then transferred to our own guts' microbiomes through this lateral gene transfer.  The results from this study are published here.  

Another study focused on mice that were fed Lactobacillus in their drinking water versus those control mice that were not.  The mice that were given the probiotic were skinnier than control mice, and had shinier coats and healthier skin.  They then discovered that it was alterations to the immune system, rather than the Lactobacillus themselves, that were causing these changes.  These results are not yet published.

Finally, Eric talked about his stool bank, OpenBiome, which we previously discussed in a separate blog post.  OpenBiome is dristributing fecal material to be used in fecal microbiota transplants (FMTs).  We have talked about FMTs in this blog extensively, and even touched on some studies that showed mice lose weight, or become less stressed, when given the microbiome of a healthy donor.  I asked Eric if any additional phenotypes were being transferred with FMTs in humans.  He mentioned in one case a patient with alopecia suddenly grew hair after the FMT, but eventually lost the hair again.  In another case he mentioned a skinny woman that became obese after treatment with FMT.  We will leave the reader to decide how these things play into the overall ethical controversy surrounding FMTs.

The microbiome and osteomyelitis, an autoinflammatory bone disease

The Gross Clinic, famous oil portrait depicting osteomyelitis surgery from 1875.

A recent paper in the journal Nature discusses experiments that provide a link between a certain gut bacteria, diet, and osteomyeltis (an autoinflammatory bone disease).  Osteomyelitis occurs when there is a bacterial infection of the bone marrow.  It is often treated with antibiotics but sometimes surgery and amputation are necessary. 

In the study, the researchers induced osteomyelitis in a group of mice.  They then gave half the mice high fat diets and half the mice low fat diets.  They discovered that the mice eating the high fat diets were protected from osteomyelitis and showed little bone inflammation, while those eating a low fat diet developed the disease.  

The discovery that diet could alter the progression of the disease led the researchers to investigate the microbiome of these mice.  The mice with low fat diets had higher amounts of Prevotella and lower amounts of Lactobacillus when compared to normal mice.  The reverse was true for the high fat diet mice, they had much less Prevotella and much more Lactobacillus in their guts, which better represents the composition in normal mice.

To further investigate if Prevotella may be causing the disease, the researchers gave antibiotics to the low fat diet mice, which destroyed the Prevotella population, and decreased the symptoms of the disease.

Finally, the researchers performed microbiome transplants into germ-free mice that were susceptible for osteomyeltis.  Any germ-free mouse that received a transplant high in Prevotella and then was fed a low fat diet developed the disease.  However, any mouse that received a transplant that was low in Prevotella, even if that mouse was on a low fat diet, did not develop the disease.  

These results show that dietary intake can alter the microbiome and greatly influence osteomyelitis outcomes.

Microbiome course begins today

There will be an online course beginning today about the microbiome.  The course will run for 6 weeks and is being taught by three scientists from the University of Colorado, Boulder, including a member of AMI's Scientific Advisory Board, Dr. Rob Knight.  Dr. Knight is one of the world's leading microbiome scientists and there will be guest appearances throughout the course by several of the preeminent individuals in the field.   

For anyone interested in learning more about the human microbiome, I highly recommend you check this out and learn about this amazing field of research.

https://www.coursera.org/course/microbiome  

New study correlates antibiotic use in infants and childhood obesity

Childhood obesity is increasing in the United States (Figure is from the CDC, not from the linked study)

One of my favorite things about working in the microbiome field is telling my friends and family about my work and about the human microbiome. In the days and weeks following my conversations, I often get emails from them about news articles they've read pertaining to the microbiome. Earlier this week, my good friend Kyle sent me an article about an important study published in JAMA Pediatrics that showed a correlation between antibiotic use in children during their first two years of life and early childhood obesity. While we see many studies in the field, there is so much going on and we can't see everything.  If any of our readers come across a study or article that may be of interest for the blog, we'd love to hear from you so please email us at blog@microbiomeinstitute.org.

In this particular study, researchers at Johns Hopkins Bloomberg School of Public Health, Children’s Hospital of Philadelphia, and University of Pennsylvania reviewed the health records of over 64,000 children seen between 2001 and 2013 in local Philadelphia health clinics. They found that children who were given several courses of antibiotics before the age of 2 (four or more courses), were more likely to become obese by the age of 5. Specifically, broad spectrum antibiotics were causing this increase in obesity while narrow spectrum antibiotics were not.  Narrow spectrum antibiotics target specific bacteria while broad spectrum antibiotics attack a much wider range of bacteria. 

People have long hypothesized and shown that the overuse of antibiotics is resulting in several public health problems in today's society, including obesity, due to their altering the composition of the gut microbiome, and this study correlates with those predictions.  Parents worry about the health of their child and may receive an antibiotic from a doctor "to be safe" in case the child has a bacterial infection that needs treatment. But children today are often being given antibiotics when they are not needed or may be receiving a broad spectrum antibiotics when a narrow spectrum antibiotic would suffice. 

We have learned countless times that overusing antibiotics, especially in children, is altering our gut bacteria and having serious implications on our health.  Antibiotics are absolutely critical to the health and wellbeing of children and adults around the world but it is important that we become better educated on this subject and ask better questions when we see a doctor, such as the likelihood of a certain infection being viral or bacterial.

In one our posts from earlier this month we talked about the research of one of our scientific advisors, Dr. Marty Blaser from NYU School of Medicine, that showed that antibiotics caused an increase in obesity in infantile mice. This is a very popular topic and I don't think this is going to be the last time we hear about it.

Quality control is critical to microbiome research

We just got back from two days in Rockville, MD for a meeting of the Microbiome Quality Control Project (MBQC).  The MBQC is a project that seeks to understand variability in microbiome data from sampling to analysis and make recommendations as to best practices.  Its steering committee includes some of the leading scientists in the microbiome field, Rob Knight, Curtis Huttenhower, and Owen White (all members of the AMI Scientific Advisory Board), along with epidemiologists from the National Cancer Institute Rashmi Sinha and Christian Abnet.  

Labs from around North America signed up to participate in two different aspects of the study, microbiome handling and bioinformatic data analysis. The labs that were involved in the handling aspect of the study received anonymized samples from a central repository and were tasked with extracting DNA from the samples and sequencing them.  They then made their data available (still anonymized) for the groups who signed up for the bioinformatics phase of the projects to analyze the data. Because all of the groups were handling and sequencing the same samples, differences in results meant that the variability was being caused by some aspect of the handling process or differences in the analysis.

At the meeting the steering committee presented the results of the study followed by a day and a half of discussion of the results and what steps could be taken to develop more standardized results, protocols, and reference materials for future microbiome studies. The results were exciting to see but even forgetting the results, the overall initiative was a huge success. This was a project that took place for over a year and all of the project's participants volunteered an enormous amount of time and conducted their research studies without receiving any funding.  It was wonderful to see a group of the world's leading scientists to come together like this with the sole goal of bettering future microbiome research.  

The AMI supports the MBQC and looks forward to being involved in the future phases of this work. As we learned at the meeting, there is so much left to be done to improve microbiome quality control and this was just the beginning.  More information about the results of the study and the meeting will be published in the coming months.