The gut microbiome may contribute to susceptibility to developing alcoholic liver disease

Alcoholic liver disease (ALD) is a major public health issue, yet the underlying mechanisms between ethanol consumption and injury to the liver are poorly understood.  Alcoholics vary in their susceptibility to developing ALD and alcoholic hepatitis (AH) despite consuming similar amounts of alcohol.  Taken together, this evidence suggests that other factors contribute to the onset and progression of ALD other than direct toxicity of alcohol.  Intestinal inflammation and pro-inflammatory bacterial products have also been observed in ALD patients and preclinical mice models, and intestinal dysbiosis has been observed in patients with alcohol dependency.  With this in mind, a team of European researchers devised a strategy to demonstrate microbiome dysbiosis as a casual driver of liver injury. 

The researchers transplanted human gut microbiota into germ-free mice, and the mice were then placed on a high-alcohol diet.  Microbiota were harvested from human alcoholic patients with or without AH (or low severity AH).  Mice transplanted with AH-microbiota had marked increases in symptoms of liver disease as compared to those mice that received microbiota transplants from non-AH alcoholic patients.  These include severe liver inflammation (including increases in T lymphocytes and natural killer cells), more necrosis in the liver, and higher intestinal permeability.  Enterobacteria counts were high in sever-AH patients and faecalibacterium genus was associated with AH-microbiota with low severity.  In an interesting spin, the researchers also transferred microbiota from an alcoholic patient without AH to mice with liver lesions.  Interestingly, mice who had received these microbiota displayed a reduction in serum alanine aminotransferase levels and a decrease in liver regeneration, suggesting that these microbiota could even possibly reverse alcohol-induced liver lesions. 

These findings not only support an association between the gut microbiome and susceptibility to developing alcoholic liver disease, but also provide evidence that these bacteria may drive disease onset.  These were important findings that support microbiota-causal effect rather than dysbiosis as a consequence of liver disease.  This data could perhaps promote development of novel diagnostic techniques that assess the gut microbiome or bacterial metabolites of alcoholic patients.  Methods such as manipulating the microbiome as a therapeutic approach for these patients could also be explored. 

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. 

Elderly people's microbiomes may contribute to their frailty

The ELDERMET program is a microbiome project in Ireland out of the University College Cork that is attempting to define the elderly microbiome and discover any associations between the microbiome and diseases linked with frailty and old age.  The team has published multiple papers from this project, some of which we have already blogged about, and last week they published another one in the ISME Journal.  In this latest paper the researchers described in fine detail just how the microbiota changes with diet within a geriatric population, and how this is actually independent of where the elderly people live.

The researchers studied the fecal microbiota of 384 elderly subjects over the course of one year.  They noticed immediately that the microbiomes clustered dependent upon whether the person was living in a nursing home or living amongst the general community.    The researchers characterized the microbiota in 4 groups based on a certain characteristics: M1, M2, M3, and M9.  M1 is a group of genera that is present in almost all subjects sampled, so it represents a core microbiome and is composed of genera such as Bacteroides, Alistipes, Parabacteroides, Faecalibacterium and Ruminococcus.   M2 is a cluster that is composed of bacteria that are associated with high-fiber diets and health, and is comprised of Coprococcus, Prevotella and Catenibacterium.  M3 is associated with folks who lived long-term residential care facilities, and consists of Anaerotruncus, Desulfovibrio and Coprobacillus genera.  Finally, M9 consists of other bacteria that were often found, like strains of Bacteroides, Parabacteroides and Alistipes.

The scientists then compared these microbiome groups with health indicators.  They discovered that highly diverse microbiomes were associated with health, especially among those living in the general community.  However, even though living in long term care facilities often increased diversity, having an M3 microbiome was overall associated with negative health.  In addition, the researchers noted that while individual foods were not strongly correlated with any health indicators, ‘healthy diets’ characterized by high fiber intake, were associated with better health than ‘unhealthy diets’.  Finally, when looking at how the microbiome changed over time, it was apparent that entering a nursing home increased the likelihood of shifting the subjects’ microbiomes to the M3 state, which is associated with bad health.  The researchers think this is likely due to the lack of fiber in nursing home food, and the high use of antibiotics.

The authors state that older people have many differences in their eating habits as compared to a normal adult population, like number of teeth, amount of chewing, and intestinal transit time, and all of these things may be contributing to the altered microbiome.    Regardless of these exogenous factors, this study reinforces the notion that lack of diet diversity and high use of drugs in nursing homes may be creating dysbioses that contribute to frailty disease.  If you have loved ones in an extended stay facility we recommend considering supplementing their diet with some fresh vegetables, so as to keep their microbiome from turning against them.

The fate of the gut microbiome following stem cell transplant

Bone marrow prior to transplant

Hematopoietic stem cell transplant (HSCT) is a difficult procedure that is usually administered to patients suffering from bone marrow or blood cancers such as multiple myeloma or leukemia.  Unfortunately, many patients who receive this treatment develop acute graft-versus-host disease (aGvHD), a multi-organ system immunologic disorder that is particularly detrimental to the gastrointestinal tract. 

In light of increasing evidence highlighting the importance of the symbiosis between the microbiome and human hosts, researchers set out to explore the fate of gut microbiota in pediatric patients who had undergone HSCT.  Specifically, phylogenetic profiles and functional properties were examined in a longitudinal analysis to develop a better understanding of the specific role the gut microbiome plays in patients who develop aGvHD following a HSTC procedure. 

Ten pediatric patients who had undergone HSTC, 5 of which had developed aGvHD, were selected for analysis.  The trajectory of the microbiota ecosystem was monitored using gene pyrosequencing of fecal samples, which were collected before, during, and after the HSTC procedure.  Collection and observation continued for 3 to 4 months.  Additionally, researchers examined short-chain fatty acid (SCFA) production samples in the patients as a measurement of microbiota metabolic activity.  Short-chain fatty acids are critical metabolites that microbiota require in order to maintain healthy physiology.  Healthy microbiota are critical toward educating the immune system and maintaining homeostasis.

Marked changes were observed in the gut microbiome populations of all 10 patients immediately following the HSTC procedure.  There was a massive invasion of new bacterial species following the procedure, with less than 10% of the original microbiota being conserved.  In particular, there was a significant loss in health-promoting bacterial species such as Faecalibacterium and Ruminococcus.  Two months after the procedures, the species richness and metabolic activities in the patients’ guts was restored. 

The patients who developed aGvHD experienced a major drop in health-promoting bacteria and higher abundances of invading bacteria as compared to non-aGvHD patients.  Interestingly, the gut microbiomes of the non- aGvHD patients contained significantly higher populations of Bacteroides phylum.  On top of this, Bacteriodes were the most abundant species observed among the original 10% of microbiota conserved through the HSTC operation. 

This study points to the importance of the gut microbiome in helping maintain healthy integrity of the gut immune system following a HSTC procedure.  The finding that having low Bacteriodes populations may be an unrecognized consequence that could lead to the development of aGvHD is particularly interesting.  Should these bacteria be as important as this data suggests, preventative microbiome-driven therapies could be explored with the aim of preventing post-HSTC procedural aGvHD onset.  A therapy that could maintain healthy Bacteriodes populations prior to HSTC operations could perhaps present a viable solution.  

Sewage accurately represents a city’s inhabitants’ microbiomes

An individual’s microbiome is sometimes indicative of his or her health, but what about the entirety of a population.  Can a city’s microbiome be indicative of the health of that city’s population?  In an article published in MBio, researchers collected sewage samples from 71 U.S. cities in the hopes that it would accurately reflect the microbiomes of that city’s citizens.

Researchers collected and sampled sewage from 71 cities and 78 waste water treatment plants across the United States, and compared it to publicly available data from the human microbiome project.  They discovered that the sewage samples were representative of the human stool samples, and that they captured 97% of the bacteria found in the typical stool. In addition, they noted that sewage samples had a greater bacterial diversity than stool samples.  The researchers also identified 27 “core” gut bacteria among all the sewage samples that they suspect are ubiquitous across the American population.

 Interestingly, the researchers were also able to use their data to predict, with 81-88% accuracy, whether the sample came from a lean or obese population. The relationship was driven mainly by an increased abundance of Bacteroides and a decreased abundance of Faecalibacterium. While Faecalibacterium are more present in high-diversity anti-inflammatory gut communities, Bacteroides are found more commonly in gut communities of human consume a diet high in animal fat.

 This study demonstrates that sampling sewage may be a practical way to attain large samples of human fecal microbiome, in order to compare populations without bias.  It must be unpleasant to work with fecal samples to begin with, so attaining samples from sewage may be an easier alternative, especially in studying populations, as opposed to individuals. 

Promoting your dog’s microbiome through functional food

Dogs are man’s best friend, but did you know that they can suffer from digestive diseases and inflammatory bowel diseases too?  A new study published in the British Journal of Nutrition aimed to investigate how dog foods could be ‘functionalized’ by the addition of potato fiber.  This prebiotic promoted the production of many important molecules and shifted the microbiome in ways that may be critical to gut health.

In the study, numerous dogs had their feces sampled for their microbiome in addition to metabolites.  A control group was fed a normal diet and an experimental group was fed the normal diet with the different amounts of potato fiber.  All of the dogs’ microbiomes were richest in Firmicutes, regardless of diet.  However, dogs given potato fiber had an increase in Firmicute abundance, as well as Bifidobacterium spp. and Lactobacillus spp.   Both Bifodobacterium and Lactobacillus are common probiotics that are shown to promote gut health in humans.  In addition, one particular bacterium, Faecalibacterium prausnitzii, was shown to proliferate after the potato fiber was added to the diet.  This bacterium has also been related to decreases in IBD in humans.  Finally, the dogs that ate potato fiber had an increase in butyrate, short chained fatty acids (SCFAs), and an overall decrease feces pH.  Each of these has been implicated with lower incidence of IBD.

This study was one of the first to investigate prebiotics in dog food.  The simple addition of potato fiber, a complex carbohydrate, had important changes on the microbiome, including the production of SCFAs which we have blogged about in the past.  Potato fiber may be an easy, inexpensive dog chow additive for all dog owners and lovers to help their pets lead happier, healthier lives.