Some of the microbiome-related papers published this month prompted active discussions on social media—highlighting just how much we’re learning, but also how hard it is to interpret the data at times. Listed here are six interesting and thought-provoking publications this month that have possible relevance to human health.
For years, a scientific debate has been ongoing about whether the human placenta harbours live microorganisms that can be considered a ‘microbiome’. While some papers have provided evidence of a placental microbiome, critics have argued that the detected microbes may have resulted from contamination. This new paper, considered the most carefully-controlled study of placental samples to date, found an absence of bacteria in most of the samples. The bacteria that were observed were chalked up to either contamination of lab reagents or to microbes ending up in the placenta through the process of labour and delivery. Some consider the matter settled; but others are taking this as a challenge to double down on their efforts to show the existence of a placental microbiome.
Here’s the joy of the microbiome field—at every turn, one of our most basic assumptions is challenged by new data. This paper provides an example: we’ve been accustomed to thinking each creature has host-imposed constraints on its microbiome. Thus, we speak about ‘human microbiomes’ versus ‘gorilla microbiomes’ versus ‘salamander microbiomes’, assuming that humans and gorillas will likely have microbiome features in common. But a new study has shown that hosts with a close evolutionary relationship don’t always have increased gut microbiota similarity.Specifically, the researchers found that humans consuming a diverse foraged diet had gut microbiomes that were similar to those of cercopithecine monkeys with similar diets; in contrast, these human microbiomes were different from apes, despite the latter being evolutionarily closer to humans. This provides evidence that in some contexts, theconstraints imposed by the host may be lessimportant than dietfor microbiome composition.The researchers say the next step is to find out the powerful nutritional drivers of the gut microbiota similarity in distantly-related hosts.
We know one microbiome may be different from another microbiome in its composition or its function; and so far, the hunt for biomarkers of health and disease has largely focused on these parameters. In this new paper, researchers put forward the idea that microbiome spatial perturbations could potentially be linked to health. They describe a method that maps out how microbes are organized in an intactfecal microbiome sample, rather than one that is homogenized in a buffer.Furthermore, they demonstrate (in mice) how diet can alter the spatial structure of the gut microbiome.
Several years ago, Gordon lab showed that malnourished children who experience growth stunting have a developmentally ‘immature’gut microbiota.They cited this as one possible reason therapeutic diets don’t always manage to restore the normal growth of these children. Then they asked: can the gut microbiota then guide the development of a better therapeutic diet? The group’s latest paper shows how they tested several therapeutic diets made up of local Bangladeshi foods, and settled on one that was able to put the children’s biomarkers (of growth, bone formation, neurodevelopment, and immune function) on par with those of healthy children. Follow-up work will undoubtedly show how this bears out for the health of the children who received the therapeutic diet.
One enticing possibility is that microbiome data could serve as a way to predict health problems before they occur. This is the latest work to show a link between microbiome function in infancy and a clinical phenotypelater in childhood. Using a subset of samples from the Canadian CHILD study, these researchers found that, as early as 3 months of age, they could detect differences in the stool samples of children who would go on to develop allergic disease as compared to those who would stay healthy. Shotgun metagenomic analysis showed fewer genes encoding both carbohydrate degradation and butyrate production; the infants who would later develop allergy showed deficiencies in genes encoding for carbohydrate active enzymes that degrade human milk oligosaccharides and plant cell walls.
This publication in mBio journal brings us to a new level of knowledge about healthy human skin throughout the lifespan. With 495 subjects spanning the ages of 9 to 78, sampled at 4 skin sites and inside the mouth, the study identified a set of variables (both intrinsic andextrinsic)that explained up to 20% of themicrobiome variability on healthy skin.The factors that predicted facial skin microbiome composition included levels of skin porphyrins (molecules synthesized by the acne-linked microbe C. acnes), as well as age, and the use of sunscreen. And while the study didn’t exactly detect an ‘anti-aging microbe’ on certain lucky people, it did uncover microbiome patterns associated with the presence of facial wrinkles and spots.
The five microbiome papers highlighted for August are representative of some important areas for scientific development in the microbiome field: microbiome-disease causality; gut microbial influences on health beyond the gastrointestinal tract (here, on cancer tumors); predicting the personalized impact of antibiotics; contributions of genes and gut microbiota to disease development; and attempts to quantify a “healthy microbiome”.
We know obesity and type 2 diabetes are associated with both gut microbiota changes and chronic low-grade inflammation – but it’s unclear whether the inflammation triggers changes in gut microbiota composition, or vice versa, or a bit of both. A new mouse study gives an indication of how the chain of events might work. Scientists started with this observation: a loss of Clostridia in the gut is associated with obesity, both in mouse models and in humans with metabolic syndrome. Then they found that when immunoglobulin A targeted Clostridia in the gut, lipid absorption in the host increased. It seems that the immune system may ‘oversee’ the gut microbial changes that lead to host metabolic problems.
A critical question for those with resected pancreatic adenocarcinoma (PDAC): what makes the difference between short-term survival (less than five years) and long-term survival? This study shows the gut microbiota could be an important factor. First, higher microbial diversity and specific taxa were observed in the tumors of those who survived longer. And humanized mouse data showed, interestingly, that mice receiving gut microbial transplants from either short-term or long-term PDAC survivors showed different patterns of tumor growth and immunosuppression. The apparent cross-talk between the gut and tumor microbiomes deserves further investigation.
Previous work has shown that while antibiotics drastically alter the gut microbiota of a host, the composition usually returns to normal after a few weeks. But a host’s response to antibiotics seems personalized—and this was the topic of a recent paper from Sokol lab in France. In the study, mice were colonized with gut microbes from one of two human donors before receiving antibiotics. The results showed the baseline gut microbiota steered the impact of antibiotics on the gut microbiota and colonic gene expression in the host. One group of mice, for instance, showed a more pronounced microbiota ‘destabilization’ than the other group. Further research could attempt to predict the host response to antibiotics and resulting health effects.
Interplay between genes, gut microbiota, and health is a hot area within microbiome science. That is to say, if genetic risk factors have been flagged for particular diseases, it’s possible that the gut microbes associated with the identified genes may be active in disease pathogenesis. A new study provides the first exploration of this concept in children with type 1 diabetes. The greatest genetic risk for type 1 diabetes is represented by class II human leukocyte antigen (HLA) allele combinations. Using fecal samples from 403 one-year-old children in a Swedish cohort, scientists found that gut microbiome composition and diversity differed based on the children’s HLA risk group and genotype. Those with HLA haplotypes conferring a neutral or decreased risk of type 1 diabetes development had a greater relative abundance of bacteria from the genera Intestinibacter and Romboutsia. This may prompt further studies exploring the interaction of genetic and environmental risk factors for type 1 diabetes, and possible early interventions for prevention of disease.
Over a decade ago, the US Human Microbiome Project set out to identify the characteristics of a “healthy microbiome”—but the microbiomes of healthy humans turned out to be so complex and variable that the definition of healthy microbiome remains elusive to this day. The International Life Sciences Institute (ILSI) in North America held a workshop focused on the following question: “Can We Begin to Define a Healthy Gut Microbiome Through Quantifiable Characteristics?” More than 40 experts came together to discuss the topic, and published their conclusions in a recent paper. The experts acknowledged the high interindividual variation observed in human gut microbiomes, and mapped out the kinds of studies that will be required to develop robust gut microbiota biomarkers of health and disease.