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.

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.

Hand washing dishes may decrease risk of allergies

A study published on Monday by the journal Pediatrics has gotten a lot of press this week because it shows a connection between allergies in children and the method by which parents wash their dishes. Parents, especially new parents, often consider good hygiene as one of the most important factors in raising their new child, but according to the hygiene hypothesis it may be true that too much cleanliness actually negatively affects a young child.  Asthma, eczema, and other autoimmune diseases are becoming more common conditions in children, and each has been linked to the hygiene hypothesis.  Researchers in Sweden reinforced this link when they discovered a possible connection between allergies in children and whether dishes were washed by hand (less clean) or by machine (more clean) in their homes.

 The researchers sent a questionnaire to parents of children aged 7-8 which was filled out by 717 families in Molndal, Sweden and 312 families in Kiruna, Sweden. The questionnaire asked many questions pertaining to the children, including previous symptoms of asthma or eczema, method of washing dishes, and if their food was farm grown or fermented.  When examining the results it is important to remember that all forms of bias cannot be eliminated when doing surveys, because, among other reasons, it is difficult to get a perfectly random sample.

Results of the study showed that there were lower instances of allergies in children whose families washed their dishes mainly by hand rather than by machine. In addition, this effect was amplified if the children ate food that was either fermented or purchased from a farm (both of which should introduce diverse bacteria to the children).  Of course, there were other variables that were not inquired in the questionnaire that are also known to decrease rates of allergies in children, and which may be related to washing dishes by hand, for example a lower socioeconomic status.  Then again, the authors suggest that hand washing dishes may reasonably be responsible for these lower rates of allergies in children of lower socioeconomic status.

So, you may be wondering how exactly this pertains to the microbiome. Hand washing dishes cleans less thoroughly than highly efficient machines, which sounds gross, but the exposure to more microbes when you are young may help develop the microbiome and immune system.  While this study is not perfect, it still shows us that exposure to bacteria is potentially a good thing for the new and developing microbiome. 

Microbiome influenced by forced versus voluntary exercise in mice

A team of scientists led by researchers at the Mayo Clinic recently discovered that forcing mice to exercise led to exacerbated inflammation, whereas allowing the mice to exercise voluntarily attenuated inflammation.  They hypothesized that the gut microbiome may be responsible for this rather peculiar phenomenon, so they repeated the study, this time measuring changes in the microbiome.  They published their results in the Journal of Applied Physiology.

The scientists separated 29 mice into three groups, a group that was forced to exercise for 40 minutes per day, a group that voluntarily exercised, and a sedentary group that did not exercise.  They conducted their study over 6 weeks, after which the mice were euthanized and their microbiomes sampled.  The researchers discovered that even though each of the groups gained approximately 10% body weight over the course of the study, their microbiomes deviated.  Interestingly, the mice that voluntarily exercised, those same mice that attenuated inflammation, had the lowest gut microbiome diversity (a trait normally related to dysbiosis and illness).  On the genus level, Mollicutes, which has been associated with ulcerative colitis, and Nauatilia were elevated in the feces of mice forced to exercise.  In addition, Turicibacter, which is related to various organisms associated with IBD, was actually decreased in the mice that voluntarily exercised.  Beyond these loose associations though, the exercise’s impact on the microbiome was not clear.

Exercise can change the microbiome, and the authors suggest that the total amount of exercise between the voluntary and forced exercise groups may have been important, as it was not controlled in this study.  Strangely, in humans, excessive exercise and no exercise at all have both been linked to gastrointestinal issues like diarrhea and constipation.  Unfortunately, the authors did not study whether the mouse version of Jillian Michaels trainers constituted forced, or voluntary exercise. 

Fecal microbiota transplant as a potential therapy for Crohn's disease

Seattle Children's Hospital

Clinicians at Seattle Children’s Hospital have found that fecal microbiota transplants (FMTs) may be a therapeutic option for patients with Crohn’s disease. Crohn’s disease (CD) is an inflammatory disease of the GI tract that is marked by an immune attack on a person’s own body, specifically in the gut.  The microbiome of CD patients is altered compared to healthy indivduals, but it is not clear if this is a cause or effect of the immune attack.  The group at Seattle Children’s Hospital hypothesized that if they could alter the microbiome of these patients that they would promote less inflammation resulting in fewer symptoms. 

The successful results were published in the journal Inflammatory Bowel Disease. They conducted fecal microbiota transplants in 9 individuals with pediatric Crohn’s disease between the ages of 12 and 19.  Patients received transplants from their parents, 7 from their mother and 2 from their father.  After two weeks, 7 of the 9 patients were in remission and at weeks six and twelve, 5 of the 9 patients were still in remission.  While the patients did have some side effects, almost all of them were mild.

The investigators looked at the differences in the microbiome between donor and recipient and what impact this had on disease.  They found that the individual who received the transplant of a microbiome that was most similar resulted in the smallest change of clinical course and the FMT recipient whose microbiome was the most different resulted in the greatest change in clinical course. They also found that increased levels of Escherichia coli correlated with increased clinical symptoms and inflammatory markers.  While it is not likely that E. coli is the cause of CD, it is an interesting observation that could be investigated to better understand what impact it has on disease progression.

This study provided evidence that the microbiome plays and important role in Crohn’s disease.  The results of this small study were promising and show that fecal microbiota transplants were generally safe and should be further investigated as a potential therapeutic option for individuals with this inflammatory disease. Further longitudinal studies are important to understand the entire impact that the FMT has on an individual.  As we have seen in previous blog posts, while it may cure the disease it is aiming to treat, there can also be other unintended consequences. 

Antibiotic resistant bacteria at UCLA and how the microbiome can prevent similar infections

Endoscopes (the instrument that resulted in infections at UCLA) in sterilization equipment

Over the past few weeks at Ronald Reagan UCLA Medical Center in Los Angeles, California, 179 patients were exposed to Carbapenem-resistant enterobacteriaceae or CRE, resulting in seven patients being infected and two deaths.  This is a lethal bacterium that is very resistant to antibiotics and has resulted in significant discussion in the press. Hospital patients with compromised immune systems are susceptible to infections passed on from other patients and hospital equipment and in the current case of CRE at UCLA, a contaminated endoscope.

Another prominent cause of infection is the bacteria enterococci, specifically vancomycin-resistant enterococci (VRE), which, as the name states, are resistant to the antibiotic vancomycin. In healthy individuals, the bacteria are not a threat and are usually killed by the immune system. In cancer patients, the elderly, transplant recipients, and other patients on antibiotics, the weakened immune system and microbiome colonization cannot fight the colonization of VRE in the gut. The result is an infection of the intestines, and possibly of the urinary tract, blood stream, and heart.

In an article published in FEMS Microbiology Letters in early February, the authors summarize research that is being done to overcome the issue of VRE infection. Infection by enterococci often occurs in patients who have taken antibiotics that deplete beneficial bacteria in the gut. One possible fix for this problem could be the administration of probiotics, live microorganisms that provide a health benefit. Unfortunately, limited research has been done in this area. In one inconclusive study, Lactobacillus rhamnosus appeared to eliminate or at least decrease the presence of VRE in the gut. Other studies suggest that it is easier to prevent infection of, rather than eradicate already present VRE.  

Another area of investigation is the use of commensal bacteria to prevent infection, or the administration of normal gut-colonizing bacteria. A popular topic in microbiome research, and one that often, and recently, appears on our blog is the treatment of infection of Clostridium difficile. One method of treatment that we frequently discuss is fecal microbiota transplant (FMT). The authors of this article suggest the use of FMTs may be able to be applied for the treatment of enterococci infection. 

Many hospital patients get sick from infections passed within the hospital, as their compromised immune systems cannot stave off infection. Hospitals are supposed be a place for getting healthier, yet we know that hospital-acquired infections are a major issue in today’s hospital systems as we have seen over the past few weeks at UCLA. New strategies for overcoming these issues are being pursued and are very important for the prevention of deaths resulting in bacterial infections passed within hospitals.    

Schizophrenia and the virome

Schizophrenia PET scan

Schizophrenia is a mental health disorder in which people cannot recognize reality, suffer from hallucinations, and experience social withdrawal.  The causes of schizophrenia are unknown, but it is thought to include genetic, environmental, psychological, and social risk factors.  As we have written about extensively in this blog, the bacteria and viruses in our body have an important connection to our brain and behavior, in what has been termed the ‘gut-brain axis’.  Considering the gut-brain axis, a team of scientists from Johns Hopkins University wondered if the microbiome, and specifically the virome, was somehow related schizophrenia.  They recently published their findings in Schizophrenia Bulletin.

The scientists sampled the throat microbiome from 74 people in the Baltimore, MD area, 41 of whom suffered from schizophrenia and 33 of whom did not.  They discovered that a specific bacteriophage (virus that infects bacteria), Lactobacillus phage phaidh, was linked to schizophrenia, which was found in 17 of the 41 schizophrenia patients, but only 1 of the 33 control individuals.  In addition, 9 of those 17 schizophrenics had a comorbid immune disorder, such as diabetes or Crohn’s disease, whereas only 2 of the remaining schizophrenics without the phage had these diseases.  The scientists also found a loose link between taking the drug valproate and occurrence of the phage.  Interestingly, this drug has been previously shown to affect the microbiome.  Finally, the existence of the phage coincided with higher levels of the bacteria that the phage attacks, Lactobacillus gasseri.  This is an unsurprising result because a phage and its target are usually found together.

The scientists acknowledge that the results of this study do not prove any real association between the microbiome and schizophrenia, but based on the results, they suggest that further research is warranted.  Notably, Lactobacillus gasseri is sometimes included in probiotics to supposedly relieve gastrointestinal issues.  However, if gasseri’s phaidh phage goes along with it, then according to this study, it may cause more harm than good.