The anorexia nervosa gut microbiome differs from healthy controls and is related to mental health

Two photographs, before and after treatment for anorexia

Anorexia nervosa is devastating condition in which an individual purposely starves themselves leading to severely low weight.  In addition, most patients with anorexia have depression, and there is a definitely mental aspect to this disease.  The disease then, has both dietary and mental components, making it extremely interesting to microbiome scientists, because the microbiome is implicated with both of these facets.  Scientists from UNC recently conducted a preliminary study on both of these aspects of the disease by comparing the microbiomes and mental state of anorexic patients before and after treatment, along with healthy controls.  They published there results last week in the journal Psychosomatic Medicine.

Sixteen patients with anorexia nervosa who sought treatment for their disease had stool samples collected at admission to the hospital as well as their mental health assessed.  Ten of these individuals that made partial recoveries (improved body mass index) were discharged from the hospital and donated stool samples and had their mental health assessed upon leaving.  The researchers discovered that the patients’ microbiomes severely lacked diversity compared to aged matched controls, and that was true for both admission and discharge from the hospital.  The scientists noted though, that the patients that left the hospital had microbiomes that more resembled the control individuals than when they entered.  For example, the anorexic patients had very little Clostridia when they entered the hospital, but these populations rebounded during treatment.  In terms of the mental health aspect of anorexia and the microbiome, the researchers found a direct association between eating disorder psychopathology and microbiome diversity, with lower diversity corresponding to worse eating disorder psychopathology.  The same was true for depression, as the degree of depression was inversely correlated with bacterial diversity.  In terms of individual families of bacteria, a lack of Ruminococcaceae had the strongest association negative mental state.

This study shows that a lack of eating decreases gut flora diversity and negatively impacts the microbiome.  While not surprising, this lack of diversity will almost certainly cause a dysbiosis that detriments many other aspects of health.  One of these, in the case of anorexia, may be mental health, but of course it is not clear which causes which, or if there is any causation or merely just correlation.  In any event, disorders that have both mental and dietary components are extremely fascinating to investigate, as it is possible the microbiome is of primary importance to these diseases.

The efficacy of drugs used to treat urinary incontinence may be dependent on the urinary tract microbiome

A very common issue among older women is urinary urgency incontinence (UUI), often referred to as an overactive or uncontrollable bladder. This is characterized by the sudden, intense need to urinate, followed by the loss of bladder control. Treatment for this problem includes solifenacin, an anticholinergic medication. Sequencing of urine bacteria has shown that UUI-affected women have different bacterial compositions than do non-UUI-affected women. This has prompted researchers at Loyola University Chicago to examine the relationship between solifenacin use and the microbiome of UUI patients. The hopes of this study was to begin understanding UUI-patients’ microbiome, in hopes of one day determining whether treatment of the microbiome would be at all beneficial to UUI patients.

Two groups of women were participants in this study: 74 UUI-affected women and 60 controls. The average age of the UUI-affected women group was 61.5 years, while that of the control group was 49 years. Urine samples were collected via transurethreal catheter. At baseline, similar amounts of bacterial DNA were detected in urine samples of both study groups; however, UUI-affected women had more cultivatable bacteria and significantly more bacterial diversity.

After testing symptom improvement following certain dosages of solifenacin, the researchers were able to conclude that certain microbiota characteristics are associated with treatment. It seems as though bacterial diversity could be used to predict treatment response, as women with higher microbial diversity responded better to treatment. It is important to remember that certain bacteria could be associated with bladder health, so the aim is not to eliminate bacteria altogether, but to identify whether bacteria could be targeted as a means of improving symptoms. The results of this study are exciting in that not only are we discovering more about the microbiome, but it could be used to treat yet another malady.

The oral microbiome of schizophrenics differs from controls

Self-portrait of Vincent van Gogh, who likely had schizophrenia

The gut-brain axis is a very intriguing field that offers a lot of promise in making progress in neurological diseases.  The science is still very new, though, so much work needs to be done in establishing any connections between the microbiome and these diseases.  The reason the gut is normally explored is because of the strong connection between the gut and the brain via the vagus nerve, which in initial studies has been shown to be an important pathway for afferent and efferent connections.  Other body microbiomes’ connections to the brain have not yet been studied.  A new study that came out last week makes a connection between the oral microbiome and schizophrenia, a disease which had previously been linked to the gut microbiome.  The results were published in the journal PeerJ.

The scientists performed whole genome sequencing on the oropharyngeal microbiomes of 16 people with schizophrenia and 16 healthy people.  Importantly, the scientists note that the people with schizophrenia were more likely to be smokers and to be overweight, two qualities that are already associated with alterations of the oral microbiome.  The results showed that the schizophrenics had lower overall diversity of their oral microbiomes compared to controls.  Specifically, lactic acid bacteria, and especially Lactobacillus gasseri, were more abundant in the mouths of those with schizophrenia, even after controlling for other variables such as age and smoking status.

While this paper does not attempt to explain why these differences occur, they are quite interesting nonetheless.  If somehow the disease state can be characterized by the oral microbiome this could be important for diagnostics.  The next step is to actually establish if any of the connections between the bacteria in the body (including the mouth) and the brain are partly responsible causing the disease.  If this is the case then not only would it help explain the environmental causes of schizophrenia, but it would also lend itself to possible microbiome treatments for the disease, such as pro- or pre-biotics.

Significant bacterial diversity found in the microbiomes of remote Amerindians

A group of Yanomami people in Demini, Brazil © Fiona Watson/Survival

The Yanomami Indians are a native people that reside in remote areas of the Amazon jungle in South America, where they live in a society devoid of westernization and modernization.  They were first contacted in the 1960s, and the Venezuelan government has since preserved isolation among these societies by preventing modern development from expanding into their lands.  From an anthropologic perspective, these people therefore represent a glimpse into the past of a hunter-gatherer subsistence living human society.  Capitalizing on this unique characteristic, researchers from several institutions led by AMI Scientific Advisory Board member Maria Gloria Dominguez Bello, set out to investigate the human microbiomes of these remote communities in a twofold manner.  Bacterial diversity of the Yanomami microbiota was characterized, concomitant to exploring bacterial and gene responses to antibiotics commonly utilized in clinics in Western societies. 

Thirty four Yanomami subjects between 4 and 50 years old were selected for analysis.  Forearm skin, oral mucosa, and fecal samples were collected for bacterial analysis and compared to subjects from the U.S., Guahibo Amerindian, and Malawian tribes (the latter two were selected for comparison, as their cultures are in transition to modernization).  E. coli cultures were examined and genomic libraries were created for further analysis of bacterial expression, functional diversity, and resistome (the collection of antibiotic resistant genes) gene expression in response to antibiotic treatment. 

The Yanomami people displayed extraordinary levels of bacterial diversity as compared to the U.S. subjects, Guahibo Amerindians, and Malawians.  Specifically, the Yanomami fecal samples were characterized by high expression of Prevotella and low expression of Bacteroide bacteria.  With respect to functional bacterial diversity, the Yanomami displayed higher fecal and skin functional diversity among the other Amerindian and U.S. subjects.  Furthermore, over-enrichment in bacteria that interact with pathways involved with protein and carbohydrate metabolism was observed in the Yanomami. 

23 antibiotics were tested on 131 E. coli strains isolated from 11 fecal samples, and sensitivity to all antibiotics was observed.  Interestingly, functional libraries created from these E. coli isolates displayed antibiotic resistant genes targeted against 8 of the 23 antibiotics.  This suggests that antibiotic resistance genes have been maintained despite the lack of apparent antibiotic selection pressure that is characteristic among Western societies. 

Results from this study indicate a greater scope of bacterial diversity in a defined group of people than ever reported before.  Furthermore, the investigation illuminated an important characteristic of the bacterial resistome, as the results indicated that resistant genes were present in a population that had not been exposed to any Westernization.  This suggests that some antibiotic resistant genes are archaic, dating back to pre-westernization times and also that westernization affects microbiome diversity.  Ultimately, this study employed a fascinating approach to investigating human microbiome divergence and evolution, in addition to providing more insight to host-species relationships with respect to pharmacologic therapies.