The microbiome’s response to the flu and its treatment

In 2013 there was an avian flu (H7N9) outbreak in China that affected 140 people, killing 46 of them.  During the outbreak doctors from one of the major hospitals in China treated 40 of these patients by giving them antivirals and antibiotics, amongst other first line treatments.  In addition, they gave probiotics along with the antibiotics to restore the gut microbiome.  All the while, they measured the patients’ microbiomes to track how they changed throughout the course of treatment.  The results of this study were published last week in the journal Nature Scientific Reports.

Twenty six patients were enrolled in the study, and each of them was given antibiotics within 6 hours of admission to the hospital.  In addition, each one was given Clostridia probiotic capsules along with the antibiotics.  Thirty one healthy control stool samples that represented the demographics of those undergoing flu treatment were also measured as a part of the study.  Before the antibiotics were taken, the patients with the flu already had altered microbiomes that were low in diversity and had lower abundances of Bacteroidetes and higher levels of Proteobacteria.  After antibiotics were given there was a dramatic shift in the microbiomes, that was characterized by a relative increase in the abundance of Escherichia coli.  In addition, the scientists noted that the probiotics were in fact increasing the amounts of Clostridia in the guts of patients who took them, and that the probiotics may have led to better clinical outcomes.  In their hospital only 20% of patients died of the flu, whereas 40% died in the rest of China.

The major takeaway from this study is the changes that the flu has on the microbiome, decreasing diversity and altering the levels of certain phyla.  The fact that the probiotics did appear to take hold and improve clinical outcomes is interesting, but the study was extremely small and limited in its scope to reach any statistically significant conclusions.  Overall though, this study suggests that if you come down with a flu that it may be wise to feed and nourish your microbiome because it is ‘getting sick’ right alongside you.

The gut microbiome of a pre-Columbian Andean mummy looks much different than our own

A photo of the mummy whose microbiome was studied

The study of ancient humans’ microbiomes is a topic of growing interest, because it is believed that these microbiomes more closely resemble native or ‘natural’ microbiomes than the ones we have today.  There have been a few studies on humans’ microbiomes at different periods of history, and another data point was added to the list last week.  Researchers from Italy and California were able to measure the microbiome of a pre-Columbian human (11th century to be exact) that was mummified naturally after he died in the cold, harsh, and high elevations of the Andes Mountains in Chile.  The researchers published their findings in the journal PLoS ONE.

The researchers sequenced the bacteria that were in the mummy’s colon, as well as the mummy’s feces.  Strikingly, around 99% of the bacteria belonged to the Firmicutes genus, mainly dominated by Clostridia, and Turicibacter.  In addition, the human appeared to have many bacteria associated with modern day diseases.  For example the mummy’s microbiome contained Clostridium difficile (the cause of C. difficile infection), Trypansoma cruzi (the cause of Chagas’ disease), and many types of human papilloma virus (HPV).  Finally, the researchers noted that many genes associated with antibiotic resistance were found in the mummy’s microbiome, long before these antibiotics were introduced.

This paper revealed many fascinating aspects about our ancient microbiomes.  First, it is interesting to see that Firmicutes dominated our ancient flora, especially because Bacteroidetes, which are much more common in our guts today, are broadly associated with health.  Also, it appears that many of the pathogens that afflict all sorts of diseases today have prehistoric counterparts, and may have been more abundant, or even more tolerable long ago.  Finally, the revelation about antibiotic resistance genes show that the mutations that cause them appear common enough that they occurred naturally in thousand year old colons.

Clinical trial for probiotics in irritable bowel syndrome fails to show efficacy

Irritable bowel syndrome is the most common functional gastrointestinal disorder, affecting about 10-15% of people in the United States alone, according to the International Foundation for Functional Gastrointestinal Disorders website. Fortunately, as described by the IFFGD, IBS is a functional disorder, meaning that while it does affect quality of life, it does not affect life expectancy. Probiotics have been studied as treatment for IBS because, as we’ve seen in many other examples of probiotic use, it is safe and rarely has any negative effects on the consumer. Some trials have shown that probiotics help relieve the symptoms of IBS; however the conclusions are controversial due to study structure and participant numbers. For this reason, scientists in Seoul, South Korea recently published a study in the Journal of Clinical Biochemistry and Nutrition, which studied the effects of a multi-species probiotic mixture on IBS symptoms using a double-blind study with a large number of participants.

Eighty-one patients participated in the 4-week-long double-blind study, with 42 people receiving a multi-species probiotic (containing Lactobacilli, Bifidobacteria, and Streptococci) and 38 people receiving a placebo. Baseline fecal samples were collected before probiotic/placebo consumption, revealing no significant difference between the two groups of participants. After consumption, the probiotic group showed a significant increase in concentrations of the probiotic bacterial strains in fecal samples, but not significant increase of levels of Bacteroidetes and Firmicutes.

In terms of symptom relief, while the probiotic group reported a greater percentage of relief, it was not significantly greater than the placebo group. This could be a classic case of the placebo effect, which is a phenomenon in which a sham treatment can actually improve symptoms because the person receiving the placebo believes it will help them. The results of this study are not concrete because there was no significant difference in symptom improvement; however there were significant increases in probiotic strains in fecal samples of the probiotic group. This study could be a step in the right direction toward relieving IBS symptoms.

Specific mushroom alters microbiome of mice to reduce obesity

Natural medicinal products are used around the world and prominently in Eastern civilizations. One such product, the Ganoderma lucidum mushroom has been used for centuries to promote better health. Scientific research has shown that polysaccharides (complex sugars) isolated from the fungus prevent fat cell formation in diabetic mice, and other isolates promote antidiabetic activity. Scientists in Taiwan were curious as to whether G. lucidum had any effect on body weight and obesity-related disorders such as chronic low-grade inflammation which leads to insulin resistance, type 2 diabetes, and fatty liver disease, and they published their results in Nature Communications.

The researchers tested whether water extract of G. lucidum mycelium (WEGL) can decrease obesity in high fat diet-fed mice (HFD).  A group of mice was fed a control chow diet, while another group was fed a high fat diet for 8 weeks. The chow and HFD-fed mice were treated daily with either water or WEGL at 2, 4, or 8% for two months.

The obese-human microbiome is often characterized by an increased Firmicutes- to-Bacteroidetes ratio. The researchers examined the gut microbiome of the mice and found that treatment of HFD-fed mice with 4% and 8% WEGL reduced the bacterial ratio to resemble one similar to that of chow-fed mice. In another test, 8% WEGL HFD-fed mice had an increased variety of bacterial species that negatively correlate with obesity, such as Parabacteroides goldsteinii, Anaerotruncus colihominis, Roseburia hominis, and more.  

WEGL fecal transplants were performed on some mice as well, which determined that it was indeed the altered gut microbiota of WEGL HFD-fed mice that is improved as the obese mice receiving the fecal transplant had reduced weight and a reduced Firmicutes-to-Bacteroidetes ratio. Overall, it appears that WEGL affects the gut microbiome of HFD-fed mice in a way that alters it to more closely resemble the microbiome of chow-fed mice. It was discovered that the high molecular weight polysaccharide fraction of WEGL may be responsible for its beneficial effects. While this is an exciting finding, this study was conducted in mice and it will be important to better understand the impacts this has on humans before people are out buying these mushrooms with the hope that it will lead to decreased obesity. 

Sex, body mass index, and dietary fiber correlated with microbiome composition

On last week’s podcast, we talked with Erica and Justin Sonnenburg about how the food we eat, and specifically dietary fiber, is important for “feeding” our microbiomes. All of the variables that influence microbiome composition are not fully understood, however research is continually being conducted to better understand what factors affect the microbiome.  To this end, a team of scientists from New York University School of Medicine set out to find how sex, body mass index (BMI), and dietary fiber intake impact the microbiome.

The scientists analyzed fecal samples from 82 individuals, 51 men and 31 women. They found that the women had different microbiome composition than the men, specifically a lower abundance of Bacteroidetes. They also found that BMI impacted microbiome diversity, specifically in women. Overweight and obese women had less diverse gut bacteria than normal weight women and women with a higher BMI also had less Bacteroidetes in their guts compared to the normal weight women.

The scientists also found that various sources of dietary fiber differentially impacted the microbiome of subjects.  Fiber intake from fruits and vegetables resulted in higher levels of Clostridia and fiber intake from beans was associated with greater abundance of Actinobacteria. It is possible that dietary fiber is influencing the microbiome by reducing gut transit time and lowering the pH. It is also possible that it is influencing systemic levels of estrogen, which could alter microbiome composition.

As the microbiome continues to be implicated in diseases, the ability to identify variables that affect the microbiome are important and can potentially be used for altering microbiota composition to prevent or possibly treat disease. 

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

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.