Diet and gut microbiomes are intricately
linked on both short and long timescales. Changes in diet can alter the microbiome, while microbes in turn allow hosts to
access novel diets. Bees are wasps that switched to a vegetarian lifestyle, and the vast majority of bees feed on pollen
Some stingless bee species, however, also collect carrion, and a few have fully reverted to a necrophagous lifestyle, relying on carrion for protein
and forgoing flower visitation altogether. These “vulture” bees belong to the corbiculate apid clade, which is known for its ancient association with a
small group of core microbiome phylotypes.
Here, we investigate the vulture bee microbiome, along with closely related facultatively necrophagous and obligately
pollinivorous species, to understand how these diets interact with microbiome structure.
Via deep sequencing of the 16S rRNA gene and subsequent community
analyses, we find that vulture bees have lost some core microbes, retained others, and entered into novel associations with
acidophilic microbes found in the environment and on carrion. The abundance of acidophilic bacteria suggests that an acidic
gut is important for vulture bee nutrition and health, as has been found in other carrion-feeding animals. Facultatively
necrophagous bees have more variable microbiomes than strictly pollinivorous bees, suggesting that bee diet may interact
with microbiomes on both short and long timescales.
Further study of vulture bees promises to provide rich insights into the role of the microbiome in extreme diet
Romboutsia timonensis was the only taxa associated with autism diagnosis
Autistic traits such as restricted interests are associated with less-diverse diet
Less-diverse diet, in turn, is associated with lower microbiome alpha-diversity
There is increasing interest in the potential contribution of the gut microbiome to autism spectrum disorder
(ASD). However, previous studies have been underpowered and have not
been designed to address potential confounding factors in a comprehensive way.
We performed a large autism stool metagenomics study (n = 247) based on participants from the Australian Autism
Biobank and the
Queensland Twin Adolescent Brain project.
We found negligible direct associations between ASD diagnosis and
the gut microbiome. Instead, our data support a model whereby ASD-related restricted interests are associated with less-diverse diet, and in
turn reduced microbial taxonomic diversity and looser stool consistency. In contrast to ASD diagnosis,
our dataset was well powered to detect microbiome associations with traits such as age, dietary intake, and stool
Overall, microbiome differences in ASD may reflect dietary
preferences that relate to diagnostic features, and we caution against claims that the microbiome has a driving role in
[Keywords: autism spectrum disorder, autism, gut microbiome,
restricted and repetitive behaviors and interests, diet, metagenomics, stool consistency, brain-gut-microbiome axis]
Animal hosts have initiated myriad symbiotic associations with microorganisms and often have maintained these symbioses
for millions of years, spanning drastic changes in ecological conditions and lifestyles. The establishment and persistence
of these relationships require genetic innovations on the parts of both symbionts and hosts.
The nature of symbiont innovations depends on their genetic population structure, categorized here as ‘open’, ‘closed’
or ‘mixed’. These categories reflect modes of inter-host transmission that result in distinct genomic features, or genomic
syndromes, in symbionts. Although less studied, hosts also innovate in order to preserve and control symbiotic
New capabilities to sequence host-associated microbial communities and to experimentally manipulate both hosts and
symbionts are providing unprecedented insights into how genetic innovations arise under different symbiont population
structures and how these innovations function to support symbiotic relationships.
Microbiomes can greatly affect the quality
of fermented food and beverages, including tea. In this study, microbial populations were characterized during black and
green tea manufacturing, revealing that tea processing steps can drive both the bacterial and fungal community
We also observed a fluctuation in the content of several tea-quality-related metabolites during processing. Caffeine and theanine were found in the same quantities in green tea
with or without leaf surface sterilization. However, the sterilization process dramatically decreased the content of total
catechins and theanine in black tea, indicating
that microbes on the surface of tea leaf may be involved in maintaining the formation of these important metabolites during
black tea processing.
This is a comparative study attempting to explain the pattern of cooperation across a number of microbial species.
Hamilton’s inclusive-fitness theory makes
the very general prediction that increased genetic relatedness should drive the evolution of cooperation. Various arguments
have dismissed the validity of this prediction in microbes, but without ever testing the broad taxonomic support for those
arguments. Here, we rehabilitate the central role of relatedness by showing that its power to predict cooperative gene
content holds across the full diversity of the human gut microbiota. Explaining broad-scale patterns is critical to a
unifying variable for predictive science and broad applications. The manipulation of relatedness may offer an opportunity
to engineering microbial communities, such as the gut microbiota.
Through the secretion of “public goods” molecules, microbes cooperatively exploit their habitat. This is known as a major driver of the functioning of
microbial communities, including in human disease. Understanding why microbial species cooperate is therefore crucial to
achieve successful microbial community management, such as microbiome manipulation.
A leading explanation is that of Hamilton’s inclusive-fitness framework. A cooperator can indirectly transmit its genes
by helping the reproduction of an individual carrying similar genes. Therefore, all else being equal, as relatedness among
individuals increases, so should cooperation. However, the predictive power of relatedness, particularly in microbes, is
surrounded by controversy.
Using phylogenetic comparative analyses across the full diversity of the human gut microbiota and six forms of
cooperation, we find that relatedness is predictive of the cooperative gene content evolution in gut-microbe genomes.
Hence, relatedness is predictive of cooperation over broad microbial taxonomic levels that encompass variation in other
life-history and ecology details.
This supports the generality of Hamilton’s central insights and the relevance of relatedness as a key parameter of
interest to advance microbial predictive and engineering science.
Humans have relied on sourdough starter microbial communities to make leavened bread for thousands of years, but only a
small fraction of global sourdough biodiversity has been characterized. Working with a community-scientist network of bread
bakers, we determined the microbial diversity of 500 sourdough starters from four continents. In sharp contrast with
widespread assumptions, we found little evidence for biogeographic patterns in starter communities. Strong co-occurrence
patterns observed in situ and recreated in vitro demonstrate that microbial interactions shape sourdough community
structure. Variation in dough rise rates and aromas were largely explained by acetic acid bacteria, a mostly overlooked
group of sourdough microbes. Our study reveals the extent of microbial diversity in an ancient fermented food across
diverse cultural and geographic backgrounds.
eLife digest: Sourdough bread is an ancient fermented food that has sustained humans around the world
for thousands of years. It is made from a sourdough ‘starter culture’ which is maintained, portioned, and shared among
bread bakers around the world. The starter culture contains a community of microbes made up of yeasts and bacteria, which
ferment the carbohydrates in flour and produce the carbon dioxide gas that makes the bread dough rise before baking.
The different acids and enzymes produced by the microbial culture affect the bread’s flavor, texture and shelf life.
However, for such a dependable staple, sourdough bread cultures and the mixture of microbes they contain have scarcely been
characterized. Previous studies have looked at the composition of starter cultures from regions within Europe. But there
has never been a comprehensive study of how the microbial diversity of sourdough starters varies across and between
To investigate this, Landis, Oliverio et al. used genetic sequencing to characterize the microbial communities of
sourdough starters from the homes of 500 bread bakers in North America, Europe and Australasia. Bread makers often think
their bread’s unique qualities are due to the local environment of where the sourdough starter was made. However, Landis,
Oliverio et al. found that geographical location did not correlate with the diversity of the starter cultures studied. The
data revealed that a group of microbes called acetic acid bacteria, which had been overlooked in past research, were
relatively common in starter cultures. Moreover, starters with a greater abundance of this group of bacteria produced bread
with a strong vinegar aroma and caused dough to rise at a slower rate.
This research demonstrates which species of bacteria and yeast are most commonly found in sourdough starters, and
suggests geographical location has little influence on the microbial diversity of these cultures. Instead, the diversity of
microbes likely depends more on how the starter culture was made and how it is maintained over time.
The gut microbiome is shaped by diet and influences host metabolism; however, these links are complex and can be unique
to each individual. We performed deep metagenomic sequencing of 1,203 gut microbiomes from 1,098 individuals enrolled in
the Personalised Responses to Dietary Composition Trial (PREDICT 1) study, whose
detailed long-term diet information, as well as hundreds of fasting and same-meal postprandial cardiometabolic blood
marker measurements were available. We found many statistically-significant associations between microbes and specific nutrients,
foods, food groups and general dietary indices, which were driven especially by the presence and diversity of healthy and
plant-based foods. Microbial biomarkers of obesity were reproducible across external publicly available cohorts and in
agreement with circulating blood metabolites that are indicators of cardiovascular disease risk. While some microbes, such
as Prevotella copri and Blastocystis spp., were indicators of favorable postprandial glucose metabolism,
overall microbiome composition was predictive for a large panel of cardiometabolic blood markers including fasting and
postprandial glycemic, lipemic and inflammatory indices. The panel of intestinal species associated with healthy dietary
habits overlapped with those associated with favorable cardiometabolic and postprandial markers, indicating that our
large-scale resource can potentially stratify the gut microbiome into generalizable health levels in individuals without
clinically manifest disease.
Metabolic responses to food influence risk of cardiometabolic disease, but large-scale high-resolution studies are
lacking. We recruited n = 1,002 twins and unrelated healthy adults in the United Kingdom to the PREDICT 1 study and assessed postprandial metabolic responses in a clinical setting and at
home. We observed large inter-individual variability (as measured by the population coefficient of variation, s.d./mean,
n%) in postprandial responses of blood triglyceride (103%), glucose (68%) and insulin (59%) following identical
meals. Person-specific factors, such as gut microbiome, had a greater influence (7.1% of variance) than did meal
macronutrients (3.6%) for postprandial lipemia, but not for postprandial glycemia (6.0% and 15.4%, respectively); genetic
variants had a modest impact on predictions (9.5% for glucose, 0.8% for triglyceride, 0.2% for C-peptide). Findings were
independently validated in a US cohort (n = 100 people). We developed a machine-learning model that predicted both
triglyceride (r = 0.47) and glycemic (r = 0.77) responses to food intake. These findings may be
informative for developing personalized diet strategies. The ClinicalTrials.gov registration identifier is
…The heritability of postprandial responses in the UK cohort was examined using classical twin methods (variance
components analyses) to establish the upper bound of what might be predicted by directly measured genetic variation.
Two-thirds of the cohort was recruited from the TwinsUK registry16, of which 230 twin pairs (n = 460;
183 monozygotic and 47 dizygotic) were studied for heritability. Additive genetic factors explained 48% of the variance in glucoseiAUC0–2h, whereas
0% of the variance in triglyceride6h-rise and 9% of the variance in
insulin2h-rise were explained in this way (Figure 3b). The estimated genetic variances in
insulin1h-rise and C-peptide1h-rise were close to 0 (Supplementary Table 4).
[Aging research over the past year, 2019. Categories include: The State of Funding, Conferences and Community, Clinical
Development, Cellular Senescence,Mitochondria in Aging, Nuclear DNA Damage, Cross-Links, Neurodegeneration, Upregulation of Cell Maintenance, In Vivo Cell
Reprogramming, Parabiosis, The
Gut Microbiome in Aging, Biomarkers of Aging, Cancer, The Genetics of Longevity, Regenerative Medicine, Odds and Ends,
Short Articles, and In Conclusion.]
As has been the case for a few years now, progress towards the implementation of rejuvenation therapies is accelerating
dramatically, ever faster with each passing year. While far from everyone is convinced that near term progress in
addressing human aging is plausible, it is undeniable that we are far further ahead than even a few years ago. Even the
public at large is beginning to catch on. While more foresightful individuals of past generations could do little more than
predict a future of rejuvenation and extended healthy lives, we are in a position to make it happen.
There is increasing interest about the interplay between host genetics and gut microbiome on human complex diseases,
with prior evidence mainly derived from animal models. In addition, the shared and distinct microbiome features among human
complex diseases remain largely unclear. We performed a microbiome genome-wide association study to identify host genetic
variants associated with gut microbiome in a Chinese population with 1475 participants. We then conducted bi-directional
randomization analyses to examine the potential causal associations between gut microbiome and human complex diseases.
We did not find evidence supporting the causal effect of gut microbiome on human complex diseases. In contrast, atrial
fibrillation, chronic kidney disease and prostate cancer, as predicted by the host genetics, had potential causal effect on
gut microbiome. Further disease-microbiome feature analysis suggested that gut microbiome features revealed novel
relationship among human complex diseases. These results suggest that different human complex diseases share common and
distinct gut microbiome features, which may help re-shape our understanding about the disease etiology in humans.
The rise of ancient genomics has revolutionised our understanding of human prehistory but this work depends on the
availability of suitable samples. Here we present a complete ancient human genome and oral microbiome sequenced from a 5700
year-old piece of chewed birch pitch from Denmark. We sequence the human genome to an average depth of 2.3× and find that
the individual who chewed the pitch was female and that she was genetically more closely related to western
hunter-gatherers from mainland Europe than hunter-gatherers from central Scandinavia. We also find that she likely had dark
skin, dark brown hair and blue eyes. In addition, we identify DNA fragments from
several bacterial and viral taxa, including Epstein-Barr virus, as well as animal and plant DNA, which may have derived from a recent meal. The results highlight the potential of
chewed birch pitch as a source of ancient DNA.
The urinary microbiome is a relatively unexplored niche despite the fact that we now know that it is not sterile.
Moreover urinary microbes, especially in ageing populations, are associated with morbidity even when infection is
subsequently not proven. We present the first large-scale study to explore factors defining urinary microbiome composition
in community-dwelling older adult women without clinically active infection. Using 1600 twins, we estimate the
contribution of genetic and environmental factors to variation in microbiome using both 16S and shotgun metagenomics. We
found that the urinary microbiome is distinct from nearby sites and is unrelated to stool microbiome. Core urinary
microbiome taxa were defined. The first component of weighted unifrac was heritable (18%) as were key taxa (e.g
Escherichia-Shigella (A>0.15)). Age, menopausal status, prior UTI and
host genetics were top among factors defining the urobiome. Increased composition was associated with older age,
contrary to previous findings.
Depression remains one of the most prevalent psychiatric disorders, with many patients not responding adequately to
available treatments. Chronic or early-life stress is one of the key risk factors for depression. In addition, a growing
body of data implicates chronic inflammation as a major player in depression pathogenesis. More recently, the gut
microbiota has emerged as an important regulator of brain and behavior and also has been linked to depression. However, how
this holy trinity of risk factors interact to maintain physiological homeostasis in the brain and body is not fully
understood. In this review, we integrate the available data from animal and human studies on these three factors in the
etiology and progression of depression. We also focus on the processes by which this microbiota-immune-stress matrix may
influence centrally mediated events and on possible therapeutic interventions to correct imbalances in this triune.
With the rising rates of obesity and associated metabolic disorders, there is a growing need for effective long-term
weight loss strategies, coupled with an understanding of how they interface with host physiology. While diet is a critical
and promising area of focus, it has been difficult to identify diets that are broadly effective in long-term weight
management. To explore the interaction between specific diets and bacteria within the gut, we tracked microbiota
composition over a 12-month period as part of a larger dietary intervention study of participants consuming either a
low-carbohydrate or low-fat diet. While baseline microbiota composition was not predictive of weight loss, each diet
resulted in substantial changes in the microbiota three months after the start of the intervention; some of these changes
were diet-specific and others tracked with weight loss. After these initial shifts, the microbiota returned near its
original baseline state for the remainder of the intervention, despite participants maintaining their diet and weight loss
for the entire study. These results suggest a resilience to perturbation of the microbiome’s starting state. When
considering the established contribution of obese-associated microbiotas to weight gain in animal models, microbiota
resilience may need to be overcome for long-term alterations to host physiology.
Synthetic gene oscillators have the potential to control timed functions and periodic gene expression in engineered
cells. Such oscillators have been refined in bacteria in vitro, however, these systems have lacked the robustness and
precision necessary for applications in complex in vivo environments, such as the mammalian gut. Here, we demonstrate the
implementation of a synthetic oscillator capable of keeping robust time in the mouse gut over periods of days. The
oscillations provide a marker of bacterial growth at a single-cell level enabling quantification of bacterial dynamics in
response to inflammation and underlying variations in the gut microbiota. Our work directly detects increased bacterial
growth heterogeneity during disease and differences between spatial niches in the gut, demonstrating the deployment of a
precise engineered genetic oscillator in real-life settings.
The progressive reduction of gut microbiome (GM) biodiversity along human evolutionary history has been found to be
particularly exacerbated in Western urban compared to traditional rural populations, and supposed to contribute to the
increasing incidence of chronic non-communicable diseases. Together with sanitation, antibiotics and C-section, the Western
diets, low in microbiota-accessible carbohydrates (MACs) while rich in
industrialized and processed foods, are considered one of the leading causes of this shrinkage. However, significant
questions remain unanswered, especially whether high-MAC low-processed diets may
be sufficient to recover GM diversity in Western urban populations. Here, we profiled the GM structure of urban
Italian subjects adhering to the modern Paleolithic diet (MPD), a dietary pattern
featured by highconsumption of MACs and low-to-zero intake of refined
sugars and processed foods, and compared data with other Italian individuals following a Mediterranean Diet (MD), as
well as worldwide traditional hunter-gatherer populations from previous publications. Notwithstanding a strong geography
effect on the GM structure, our results show an unexpectedly high degree of GM biodiversity in MPD subjects, which well approximates that of traditional populations. Increasing the
consumption of MACs at the expense of refined sugars, and minimizing the intake
of processed foods, both hallmarks of the MPD, could be the key to rewild the
Western microbiota, counteracting the loss of GM diversity and thus restoring evolutionarily important functionality
to our gut for improved human health.
The trillions of microorganisms that live in association with the human body (microbiota) are critical for human health
and disease, but there is a limited understanding of how cultural and environmental factors shaped our microbiota diversity
through time. However, biomolecular remnants of the human oral microbiota—recovered from the calcified dental plaque
(calculus) of our long-dead ancestors—are providing a new means of exploring this key relationship of our evolutionary
history. Here, we correlate extensive experimental, archaeological, and biological metadata with 128 ancient dental
calculus specimens from Medieval and Post-Medieval London, UK (1066 – 1853 CE). We identify a statistically-significant association between microbiota and oral geography (i.e. tooth
type and tooth surface), which has confounded ancient microbiota studies to date. By controlling for oral geography,
however, we identify the first associations between ancient microbiota and cultural and environmental signatures. We find
significant links between ancient British microbiota structure and health, including skeletal markers of stress that may
reflect low socioeconomic status. Furthermore, this study provides baseline data to
explore factors that drive microbiota differentiation within and between ancient populations and highlights the potential
of ancient microbiota to infer detailed health and sociocultural information about the past.
Dysbiosis is one of the major changes in aging that leads to an accumulation of toxic microbial metabolites. The aim of
this study was to evaluate the effect of a test food containing components of citrus, carrot, spinach and tomato on gut
microbiota and age-related metabolites in senior dogs. The study was conducted on 36 dogs between 8 and 13 years of age.
All dogs were maintained on a control food (control 1), which used corn as major source of fiber. After 30 days, the dogs
were divided into two groups of 18 dogs. One of the groups received the test food for 30 days while the other group
received the control 2 food, containing multiple whole grains as the test food but without the above added sources of fiber
present in the test food. After a washout period on the control 1 food for 30 days, a cross-over was performed so that the
test or the control 2 food was fed for 30 days to those dogs which had not yet been fed that food. Samples from feces and
blood were collected after each 30 days period to analyze changes in gut microbial composition and metabolites. The
consumption of the test food led to increased proportions of Adlercreutzia, Oscillospira,
Phascolarcobacteria, Faecalibacterium and Ruminococcus, Christensenellaceae,
Ruminococcaceae, Cyanobacteria and Acidobacteria and decreased proportions of
Megamonas, Salmonella, Enterobacteriaceae and Fusobacterium. Pets had higher levels of
glycerol and fatty acids and lower levels of pyrraline and mucin amino acids in feces. The test food also reduced
circulating levels of pyrraline, symmetric dimethylarginine and phenolic uremic toxins, including the microbial brain
toxin, 4-ethylphenyl sulfate. Christensenellaceae abundance was strongly associated with the observed health
benefits. Fermentable fibers from fruits and vegetables enhance health in senior dogs by modulating the gut bacteria and
metabolites involved in aging, kidney, brain and gut health.
Artificial gut models provide unique opportunities to study human-associated microbiota. Outstanding questions for these
models’ fundamental biology include the timescales on which microbiota vary and the factors that drive such change.
Answering these questions though requires overcoming analytical obstacles like estimating the effects of technical
variation on observed microbiota dynamics, as well as the lack of appropriate benchmark datasets. To address these
obstacles, we created a modeling framework based on multinomial
logistic-normal dynamic linear models (MALLARDs) and performed dense longitudinal sampling of replicate artificial human guts over
the course of 1 month. The resulting analyses revealed that when observed on an hourly basis, 76% of community variation
could be ascribed to technical noise from sample processing, which could also skew the observed covariation between taxa.
Our analyses also supported hypotheses that human gut microbiota fluctuate on sub-daily timescales in the absence of a host
and that microbiota can follow replicable trajectories in the presence of environmental driving forces. Finally, multiple
aspects of our approach are generalizable and could ultimately be used to facilitate the design and analysis of
longitudinal microbiota studies in vivo.
Recent studies suggest that alterations in the gut phagobiota may contribute to pathophysiological processes in mammals;
however, the association of bacteriophage community structure with Parkinson’s disease (PD) has not been yet characterized.
Towards this end, we used a published dataset to analyse bacteriophage composition and determine the phage/bacteria
ratio in faecal samples from drug-naive PD patients and healthy participants. Our analyses revealed significant alterations
in the representation of certain bacteriophages in the phagobiota of PD patients. We identified shifts of the
phage/bacteria ratio in lactic acid bacteria known to produce dopamine and regulate intestinal permeability, which are major factors
implicated in PD pathogenesis. Furthermore, we observed the depletion of Lactococcus spp. in the PD group, which
was most likely due to the increase of lytic c2-like and 936-like lactococcal phages frequently present in dairy products.
Our findings add bacteriophages to the list of possible factors associated with the development of PD, suggesting that gut
phagobiota composition may serve as a diagnostic tool as well as a target for therapeutic intervention, which should be
confirmed in further studies. Our results open a discussion on the role of environmental phages and phagobiota composition
in health and disease.
Literature regarding the differences in gut microbiota between exclusively breastfed (EBF) and non-EBF infants is meager with large variation
in methods and results. We performed a meta-analysis of seven studies (a total of 1825 stool samples from 684 infants)
to investigate effects of EBF compared to non-EBF on infant gut microbiota across different populations. In the first 6 months of life,
overall bacterial diversity, gut microbiota age, relative abundances of Bacteroidetes and Firmicutes and
microbial-predicted pathways related to carbohydrate metabolism were consistently increased; while relative abundances of
pathways related to lipid, vitamin metabolism and detoxification were decreased in non-EBF vs.EBF infants. The perturbation in
microbial-predicted pathwaysassociated with non-EBF was larger in infants
delivered by C-sectionthan delivered vaginally. Longer duration of EBF
mitigateddiarrhea-associated gut microbiota dysbiosis and the effects of EBF persisted after 6 months of age. These consistent findings across vastly different
populations suggest that one of the mechanisms of short and long-term benefits of EBF may be alteration in gut microbes.
In animals, commensal microbes modulate various physiological functions, including behavior. While microbiota exposure
is required for normal behavior in mammals, it is not known how widely this dependency is present in other animal species.
We proposed the hypothesis that the microbiome has a major influence on the behavior of the vinegar fly (Drosophila
melanogaster), a major invertebrate model organism. Several assays were used to test the contribution of the
microbiome on some well-characterized behaviors: defensive behavior, sleep, locomotion, and courtship in microbe-bearing,
control flies and two generations of germ-free animals. None of the behaviors were largely influenced by the absence of a
microbiome, and the small or moderate effects were not generalizable between replicates and/or generations. These
results refute the hypothesis, indicating that the Drosophila microbiome does not have a major influence over
several behaviors fundamental to the animal’s survival and reproduction. The impact of commensal microbes on animal
behaviour may not be broadly conserved.
The composition of the gut microbiome in industrialized populations differs from those living traditional lifestyles.
However, it has been difficult to separate the contributions of human genetic and geographic factors from
lifestyle/modernization. Here, we characterize the stool bacterial composition of four Himalayan populations to
investigate how the gut community changes in response to shifts in human lifestyles. These groups led seminomadic
hunting-gathering lifestyles until transitioning to varying dependence upon farming. The Tharu began farming 250–300 years
ago, the Raute and Raji transitioned 30–40 years ago, and the Chepang retain many aspects of a foraging lifestyle. We
assess the contributions of dietary and environmental factors on their gut microbiota and find that the gut microbiome
composition is statistically-significantly associated with lifestyle. The Chepang foragers harbor elevated abundance of
taxa associated with foragers around the world. Conversely, the gut microbiomes of populations that have transitioned to
farming are more similar to those of Americans, with agricultural dependence and several associated lifestyle and
environmental factors correlating with the extent of microbiome divergence from the foraging population. For example, our
results show that drinking water source and solid cooking fuel are statistically-significantly associated with the gut
microbiome. Despite the pronounced differences in gut bacterial composition across populations, we found little differences
in alpha diversity across populations. These findings in genetically similar populations living in the same geographical
region establish the key role of lifestyle in determining human gut microbiome composition and point to the next
challenging steps of isolating dietary effects from other factors that change during modernization.
Our knowledge of the relationship between the gut microbiome and health has rapidly expanded in recent years. Diet has
been shown to have causative effects on microbiome composition, which can have subsequent implications on health.
Soylent 2.0 is a liquid meal replacement drink that satisfies nearly 20% of all recommended daily intakes per serving.
This study aims to characterize the changes in gut microbiota composition resulting from a short-term Soylent diet.
Fourteen participants were separated into two groups: 5 in the regular diet group and 9 in the Soylent diet group. The
regular diet group maintained a diet closely resembling self-reported regular diets. The Soylent diet group underwent three
dietary phases: A) a regular diet for 2 days, B) a Soylent-only diet (five servings of Soylent daily and water as needed)
for 4 days, and C) a regular diet for 4 days. Daily logs self-reporting diet, Bristol stool ratings, and any abdominal
discomfort were electronically submitted. Eight fecal samples per participant were collected using fecal sampling kits,
which were subsequently sent to uBiome, Inc. for sample processing and V4 16S rDNA sequencing. Reads were clustered into operational taxonomic units(OTUs) and taxonomically identified against the GreenGenes 16S database. We find that an
individual’s alpha-diversity is not significantly altered during a Soylent-only diet. In addition, principal coordinate
analysis using the unweighted UniFrac distance metric shows samples cluster strongly by individual and not by dietary
phase. Among Soylent dieters, we find a statistically-significant increase in the ratio of Bacteroidetes to
Firmicutes abundance, which is associated with several positive health outcomes, including reduced risks of
obesity and intestinal inflammation.
Human gut microbiome composition is shaped by multiple host intrinsic and extrinsic factors, but the relative
contribution of host genetic compared to environmental factors remains elusive. Here, we genotyped a cohort of 696 healthy
individuals from several distinct ancestral origins and a relatively common environment, and demonstrate that there is no
statistically-significant association between microbiome composition and
ethnicity, single nucleotide polymorphisms (SNPs), or overall genetic
similarity, and that only 5 of 211 (2.4%) previously reported microbiome-SNP associations replicate in our cohort. In contrast, we find similarities in the microbiome
composition of genetically unrelated individuals who share a household. We define the term biome-explainability as
the variance of a host phenotype explained by the microbiome after accounting for
the contribution of human genetics. Consistent with our finding that microbiome and host genetics are largely independent,
we find significant biome-explainability levels of 16–33% for body mass index (BMI), fasting glucose, high-density lipoprotein (HDL) cholesterol, waistcircumference, waist-hip ratio (WHR), and lactose consumption. We further show that several human phenotypes can be
predicted substantially more accurately when adding microbiome data to host genetics data, and that the contribution of
both data sources to prediction accuracy is largely additive. Overall, our results suggest that human microbiome
composition is dominated by environmental factors rather than by host genetics.
Choosing the right nutrients to consume is essential to health and wellbeing across species. However, the factors that
influence these decisions are poorly understood. This is particularly true for dietary proteins, which are important
determinants of lifespan and reproduction. We show that in Drosophila melanogaster, essential amino acids (eAAs)
and the concerted action of the commensal bacteria Acetobacter pomorum and Lactobacilli are critical
modulators of food choice. Using a chemically defined diet, we show that the absence of any single eAA from the diet is
sufficient to elicit specific appetites for amino acid (AA)-rich food. Furthermore, commensal bacteria buffer the animal
from the lack of dietary eAAs: both increased yeast appetite and decreased reproduction induced by eAA deprivation are
rescued by the presence of commensals. Surprisingly, these effects do not seem to be due to changes in AA titers,
suggesting that gut bacteria act through a different mechanism to change behavior and reproduction. Thus, eAAs and
commensal bacteria are potent modulators of feeding decisions and reproductive output. This demonstrates how the
interaction of specific nutrients with the microbiome can shape behavioral decisions and life history traits.
What animals, including humans, choose to eat has a tremendous impact on health and wellbeing. Though intake of dietary
proteins and amino acids is essential for animals, excessive consumption of these nutrients is known to have detrimental
effects. Many animals, therefore, execute precise control over the intake of these key nutrients. However, the factors
controlling protein appetite are poorly understood. Here, we show that in the vinegar fly Drosophila melanogaster,
essential amino acids and gut bacteria are key modulators of protein appetite. Lack of any one essential amino acid from
the diet produces a strong and specific appetite for proteinaceous or amino acid–rich food. However, flies with an
appropriate microbiome do not develop this protein appetite. Specifically, two gut bacteria species, Acetobacter
pomorum and Lactobacilli, work together to suppress protein appetite. Furthermore, we show that flies lacking
dietary essential amino acids have reduced reproductive output, an effect which is also rescued by gut bacteria. Finally,
based on metabolite measurements, we propose that the influence of bacteria on host physiology and behavior is not mediated
by changing amino acid levels. Our study demonstrates how the interaction of specific nutrients with the microbiome can
shape behavior and animal fitness and suggests that they do so through a novel mechanism.
The FDA approved drugrapamycin increases lifespan in rodents and delays age-related dysfunction in rodents and humans.
Nevertheless, important questions remain regarding the optimal dose, duration, and mechanisms of action in the context of
Here we show that 3 months of rapamycin treatment is sufficient to increase life expectancy by up to 60% and improve
measures of healthspan in middle-aged mice. This transient treatment is also associated with a remodeling of the microbiome, including dramatically increased prevalence
of segmented filamentous bacteria in the small intestine. We also define a dose in female mice that does not extend
lifespan, but is associated with a striking shift in cancer prevalence toward aggressive hematopoietic
cancers and away from non-hematopoietic malignancies.
These data suggest that a short-term rapamycin treatment late in life has persistent effects that can robustly delay
aging, influence cancer prevalence, and modulate the microbiome.
Microbes in the gastrointestinal tract are under selective pressure to manipulate host eating behavior to increase their
fitness, sometimes at the expense of host fitness. Microbes may do this through two potential strategies: (1) generating
cravings for foods that they specialize on or foods that suppress their competitors, or (2) inducing dysphoria until we eat
foods that enhance their fitness. We review several potential mechanisms for microbial control over eating behavior
including microbial influence on reward and satiety pathways, production of toxins that alter mood, changes to receptors
including taste receptors, and hijacking of the vagus nerve, the neural axis between the gut and the brain. We also review
the evidence for alternative explanations for cravings and unhealthy eating behavior. Because microbiota are easily
manipulatable by prebiotics, probiotics, antibiotics, fecal transplants, and dietary changes, altering our microbiota
offers a tractable approach to otherwise intractable problems of obesity and unhealthy eating.
“Human genetics shape the gut microbiome”, Julia K. Goodrich, Jillian L. Waters, Angela C. Poole, Jessica L. Sutter, Omry Koren, Ran Blekhman, Michelle Beaumont,
William Van Treuren, Rob Knight, Jordana T. Bell, Timothy D. Spector, Andrew G. Clark… (2014):
Host genetics and the gut microbiome can both influence metabolic phenotypes. However, whether host genetic variation
shapes the gut microbiome and interacts with it to affect host phenotype is unclear. Here, we compared microbiotas across
>1,000 fecal samples obtained from the TwinsUK population, including 416 twin pairs. We identified many microbial taxa
whose abundances were influenced by host genetics. The most heritable taxon, the family Christensenellaceae, formed a
co-occurrence network with other heritable Bacteria and with methanogenic Archaea. Furthermore, Christensenellaceae and its
partners were enriched in individuals with low body mass index (BMI). An obese-associated microbiome was amended with Christensenella minuta, a
cultured member of the Christensenellaceae, and transplanted to germ-free mice. C. minuta amendment reduced weight gain and
altered the microbiome of recipient mice. Our findings indicate that host genetics influence the composition of the human
gut microbiome and can do so in ways that impact host metabolism.
Current antibiotics tend to be broad spectrum, leading to indiscriminate killing of commensal bacteria and accelerated
evolution of drug resistance. Here, we use CRISPR-Cas technology to create
antimicrobials whose spectrum of activity is chosen by design. RNA-guided
nucleases (RGNs) targeting specific DNA sequences
are delivered efficiently to microbial populations using bacteriophage or bacteria carrying plasmids
transmissible by conjugation. The DNAtargets of RGNs can be undesirable genes or polymorphisms, including antibiotic resistance and
virulence determinants in carbapenem-resistant Enterobacteriaceae and enterohemorrhagic Escherichia coli. Delivery of
RGNs significantly improves survival ina Galleria mellonella infection
model. We also show that RGNs enable modulation of complex bacterial populations
by selective knockdown of targeted strains based on genetic signatures. RGNs
constitute a class of highly discriminatory, customizable antimicrobials that enact selective pressure at the
DNA level to reduce the prevalence of undesired genes, minimize off-target
effects and enable programmable remodeling of microbiota.