Fish oil may be important to altering the microbiome, reducing anxiety

Last week we published a blog on the gut-brain axis, and the various associations between brain health and the gut microbiome.  One of the ailments we discussed was depression, which is often studied in mice by inducing early life stress on the mice.  One way to do this is by separating mice from their mothers for hours at a time at a young age.  The Maternal Separation model, as it is known, causes stress and anxiety in these mice, but more importantly, research has shown that it creates a dysbiosis of their gut microbiomes as well.  Many scientists believe the dysbiosis may be implicated in causing some of the stress phenotypes, and so reversing this dysbiosis could have therapeutic value.  Researchers from the University College Cork, in Cork Ireland, experimented with N-3 polyunsaturated fatty acids (PUFAs), like those found in fish oil, in these maternally separated mice, and found they may be important to preventing the dysbiosis.  They published their findings in the journal PLoS ONE.

In the study, the researchers separated mice into two groups, one underwent maternal separation, and the other had a normal upbringing.  Within each group the mice were separated into two more groups, one that received fish oil supplements and the other that didn’t.  Over the course of 17 weeks each groups’ feces were sampled for their microbiomes.  The Maternal separation tended to decrease the bacteroidetes to firmicutes ratio of the mice’s microbiome, which has previously been linked to depression in humans.  Interestingly, supplementation with the fish oil increased this ratio in those maternally separated mice.  In addition, the fish oil also increased the concentration of bacteria that were higher in non-separated mice, such as populations of Rikenella.  Finally, the fish oil increased the amount of butyrate producing bacteria, and as we have seen many times before, butyrate and other short chained fatty acids (SCFAs) are often associated with health.

Overall this study showed that fish oil shifted stressed mice’s microbiome to a more natural state, presumably helping them in the process.  While the scientists did not directly measure stress levels in these mice to support the microbiome connection, hopefully that will be part of a follow up study.  The scientists noted that fish oil is clinically shown to reduce inflammation, and made it a point to connect the stress in the mice to systemic inflammation.  Systemic inflammation is also mediated by the microbiome.  Indeed, people that have inflammation from IBD, for example, do tend to have more stress and anxiety.  In the end, fish oil could make for an interesting prebiotic to shift the microbiome, counteract inflammation, and improve mental health. 

Gut bacteria may help prevent asthma in children

The world has seen an explosive rise in asthma over the past three decades. Such a rise in prevalence cannot be only a result of genetic variation and leads us to believe that environmental factors play an important role in this change. There are several possible explanations for this including what we call the “hygiene hypothesis”, or the idea that we now live in an environment that is too clean and we are no longer exposed to the bacteria and germs that earlier generations were exposed to. Another possible explanation is as the world changes and becomes more modern, these environmental changes are affecting our microbiome and the “normal” microbiome is shifting to a new normal.

To better understand why some children are at high risk for becoming asthmatic, scientists in Canada studied the microbiome of 319 children in the Canadian Healthy Infant Longitudinal Development (CHILD) Study. They sequenced fecal samples from the children and found that 4 groups of bacteria that were decreased in prevalence compared to the children without asthma. Bacteria from the genus Lachnospira, Veillonella, Faecalibacterium, and Rothia (FLVR) were at lower levels after 3 months for the children at high risk for asthma however over time, this leveled out and was similar to the children not at risk for asthma.

The study did not identify what exactly caused these differences as there could be several reasons for these differences including antibiotic use, the method in which the child was delivered either vaginally or by C-section, and if the child was breastfed or not. It is also possible and maybe even likely that some of the mother’s behaviors during the pregnancy such as diet could play an important role in the early development of the child’s microbiome.

The next obvious question is what can we do about this? Does this mean that we can now treat children that are deficient of these bacteria and they won’t get asthma? While it sounds simple, we don’t yet know too much about these bacteria and it will be important to better understand the impact his would have on the rest of development. Promising results from this study did show that when mice with low levels of FLVR were treated with probiotic samples of the bacteria, it protected them from getting asthma.

This is a very exciting study that may lead to new diagnostics for asthma and with more research and understanding, allow us to prevent the disease from developing. 

Chronic kidney disease and its effect on microbiome metabolism

Patient receiving dialysis

A substantial body of evidence points to the importance of renal filtration and the elimination of microbiome-derived metabolites.  Chronic kidney disease can lead to renal failure, which can have detrimental consequences for the elimination of microbiome metabolites.  Specifically, p­­-cresyl sulfate and indoxyl sulfate are cometabolites between human metabolism and microbiome fermentation.  Kidney failure or loss of renal function can lead to retention of these metabolites, and they can induce toxic harm by remaining in systemic circulation.  While there has been significant interest in this field, much is unknown regarding CKD’s influence on microbiota function and metabolism.  Researchers in Belgium sought to address this and identify what role CKD would have on the microbiota metabolism in the colon in patients on hemodialysis. 

The experimenters examined 20 patients on hemodialysis.  These fecal metabolites profiles of these patients were compared to 20 healthy controls using gas chromatography-mass spectrometry.  Initial observations revealed that healthy controls had a significantly higher number of volatile organic compounds (VOCs) – an indicator of microbiota metabolism - as compared to the patients on hemodialysis.  After adjusting the data for statistical confounders and discriminating VOCs between groups, the researchers determined that 81 individual VOCs were significantly different between hemodialysis patients and healthy controls.  Consistent with previous findings and known clinical conditions, both p-cresol and indole were significantly upregulated in hemodialysis patients.  A major confounder in this study is diet, as hemodialysis patients are on a very restricted diet, and as we know, dietary intake impacts microbiome composition and metabolism.  The researchers conducted the same analysis with the hemodialysis patients with household contacts who were on the same diets.  Interestingly, no significant difference in VOCs was observed between groups. 

The researchers demonstrated that CKD patients on hemodialysis experience an altered microbiota metabolism; however, dietary influence may be driving this effect rather than loss of renal function.  It was good to see the researchers included the household controls, as this evidence suggests renal function by itself may not have direct impacts on gut microbiota function.  Regardless, much of the CKD-microbiome research to this date has focused on the microbiome’s role in CKD or CKD-mediated downstream maladies.  It was interesting to see a study that took the opposite approach, as we know microbiome health is important for homeostatic mechanisms that maintain a healthy body.  

We all emit our own 'microbial cloud'

Every individual has a microbiome compiled of millions of bacteria, fungi, viruses, and other microorganisms that is unique for each one of us. Whenever we travel to a new location and sit down or touch something, we are spreading our microbiome to that new location. A lot of research has gone into this phenomenon and is called the microbiome of the built environment. A new study out of the University of Oregon has expanded on this understanding and has described what they call a “microbial cloud”.

The scientists found that individuals not only spread their microbiome to new locations through direct contact but the microorganisms on our body are also dispersed into the air making up this microbial cloud. To better understand this, the scientists had 11 individuals sit in an enclosed room for 4 hours and they analyzed the DNA from the bacteria in the air. They found that when each individual sat in the room, there were thousands of bacteria in the room and everyone’s was distinct. They were able to identify specific characteristics of the people such as if it was a man or a woman.

The bacterial combinations found in the room could be linked back to specific individuals even after the person inhabited the room for only 4 hours. There were specific groups of bacteria like Streptococcus, often found in the mouth, as well as Propionibacterium and Corynebacterium, often found on the skin, that were most useful in identifying the individuals. While these bacteria were found around all the study participants it was the combination of bacteria that was key to identifying the individuals.

This finding could have several important applications. One often-discussed application of the microbiome is its use in forensic applications. It may be possible to use this ability to identify people and know if they were in a room or not to see if someone committed a crime, though it is not clear if it will be possible to identify people in a crowd of other individuals. Other applications include understanding the spread of infectious disease between individuals and within buildings. This is an exciting new development and I am certain we will see more research looking at our microbial clouds in the future.

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.

New study shows how E. coli and B. theta grow in the gut mucus

The mucosal membrane continues to be one of the most intriguing and vexing components of the gut microbiome.  It is the interface between the body and the environment, it is inhabited many bacteria, and it is a nutritional source that shapes the populations in the gut.  There is still very little known about the specific interactions between gut mucous and bacteria, but this critical system is rapidly being studied.  In the most recent advance, scientists from Switzerland and Germany examined two very different gut bacteria that fill different mucosal niches. They published their results in the journal Nature Communications.  The two bacteria they studied were Bacteroides thetaiotaomicron (B. theta) and Escherichia coli.  B. theta is a slow growing bacteria that has high metabolic flexibility that is capable of directly using gut mucins as an energy source.  E. coli is a fast growing bacteria that is much more limited in its metabolism and can’t directly use the carbohydrates in the gut, but can take hold and rapidly proliferate after a course of antibiotics. 

The researchers meticulously researched gnotobiotic mice and made many discoveries about bacteria in their mucous.  First, they discovered that the mucosal microbiome varies across its thickness, and is sterile closest to the intestines, but rich in life closest to the lumen.  In addition, they noted that the luminal microbiome is distinct from the mucosal microbiome, even though the mucous is constantly being shed into the lumen.  To this end, they confirmed that with regards to E. coli, these bugs replicate faster than they are shed (in about 3 hours in the mucous but 8 hours in the lumen), and that their persistence is due to replication rather than uptake from the lumen.  How though, can E. coli thrive with their limited ability to break down mucins?  The scientists learned that they likely metabolize iron, in addition to atypical carbon sources such as fatty acids and glycerol.  B. theta, on the other hand, has a huge repertoire of genes to break down mucins.  They do, though, have the ability to leave the mucins and form biofilms on bits of food, such as fiber, that pass through the lumen, and this is one way they travel through the gut.  Regardless of whether they are in the lumen or the mucins they proliferate at the same rate.

Each of these bacteria occupy different niches in the gut, and each is important to our health.  The discovery that E. coli can use iron for metabolism is particularly interesting, as chemotrophy is not normally considered as important in the body, and may be important to iron regulation.  As more research is published the mucous appears to be ‘where the rubber meets the road’ in the microbiome, and new discoveries in this area will be crucial to our overall understanding of the microbiome’s interaction with the body.