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“Anatomy Promotes Neutral Coexistence of Strains in the Human Skin Microbiome”, Conwill et al 2022

“Anatomy promotes neutral coexistence of strains in the human skin microbiome”⁠, Arolyn Conwill, Anne C. Kuan, Ravalika Damerla, Alexandra J. Poret, Jacob S. Baker, A. Delphine Tripp et al (2022-01-06; similar):

  • C. acnes lineages coexist across an individual’s skin but not within the same pore
  • Colonies isolated from the same skin pore are nearly clonal (<1 mutation apart)
  • Neutral bottlenecking rather than selection drives low within-pore diversity
  • Population fragmentation limits competition between C. acnes genotypes

What enables strains of the same species to coexist in a microbiome? Here, we investigate whether host anatomy can explain strain co-residence of Cutibacterium acnes, the most abundant species on human skin.

We reconstruct on-person evolution and migration using whole-genome sequencing of C. acnes colonies acquired from healthy subjects, including from individual skin pores, and find considerable spatial structure at the level of pores. Although lineages (sets of colonies separated by <100 mutations) with in vitro fitness differences coexist within centimeter-scale regions, each pore is dominated by a single lineage. Moreover, colonies from a pore typically have identical genomes. An absence of adaptive signatures suggests a genotype-independent source of low within-pore diversity.

We therefore propose that pore anatomy imposes random single-cell bottlenecks; the resulting population fragmentation reduces competition and promotes coexistence. Our findings suggest that therapeutic interventions involving pore-dwelling species might focus on removing resident populations over optimizing probiotic fitness.

[Media:

C. acnes is naturally occurring, and the most abundant bacteria on skin. Its link to acne⁠, the skin disease, is not clear, said Tami Lieberman, a professor at M.I.T. and an author of the new paper. If biologists want to unpack the relationship between your face’s inhabitants and its health, it will be an important step to understand whether varying strains of C. acnes have their own talents or niches, and how the strains are distributed across your skin.

To collect their samples, Dr. Lieberman and her colleagues used commercially available nose strips and old-fashioned squeezing with a tool called a comedone extractor. They then smeared samples, each a bit like a microscopic glacial core, from within pores on Petri dishes. They did the same with samples from toothpicks rubbed across the surface of participants’ foreheads, cheeks and backs, which picked up bacteria living on the skin’s surface rather than in the pores. They allowed the bacteria to grow, then sequenced their DNA to identify them.

Each person’s skin had an unique combination of strains, but what surprised the researchers most was that each pore housed a single variety of C. acnes. The pores were different from their neighbors, too—there was no clear pattern uniting the pores of the left cheek or forehead across the volunteers, for instance.

What’s more, judging from the sequencing data, the bacteria within each pore were essentially identical. “There’s a huge amount of diversity over one square centimeter of your face”, said Arolyn Conwill, a postdoctoral researcher who is the study’s lead author. “But within a single one of your pores, there’s a total lack of diversity.”

What the scientists think is happening is that each pore contains descendants of a single individual. Pores are deep, narrow crannies with oil-secreting glands at the bottom, Dr. Lieberman said. If a C. acnes cell manages to get down there, it may proliferate until it fills the pore with copies of itself. This would also explain why strains that don’t grow very quickly manage to avoid being outcompeted by speedier strains on the same person. They’re not competing with each other; they’re living side by side in their own walled gardens.

Intriguingly, these gardens are not very old, the scientists think. They estimate that the founding cells in the pores they studied took up residence only about one year before. What happened to the bacteria that previously lived there? The researchers don’t know—perhaps they were destroyed by the immune system, fell prey to viruses or were unceremoniously yanked out by a nose strip, clearing the way for new founders.]

[This raises a lot of questions about acne. If each pore is clonal, then presumably each acne cyst/​instance is also clonal. So it’s not a ‘community’ effect—is there a specific bacteria which runs amok in each pore? Or do the acne instances all share some specific mutations? And if they turn over on an annual basis, why do many cysts seem to recur in the same spot? (Or do they not, and merely recur in an adjacent spot where an acne pore managed to colonize neighboring pores?) Since acne takes time to form, does this suggest that a reason Westerners get so much acne compared to other civilizations is that being indoors or otherwise so Western reduces turnover speed, and so the reason acne is practically unknown to hunter-gatherers etc is something like “they get so much sunlight that every pore is nuked by UV light before the bad bacteria can go bad and then the pore is immediately recolonized”?]

“Longevity, Cellular Senescence and the Gut Microbiome: Lessons to Be Learned from Crocodiles”, Siddiqui et al 2021

“Longevity, cellular senescence and the gut microbiome: lessons to be learned from crocodiles”⁠, Ruqaiyyah Siddiqui, Sutherland Maciver, Adel Elmoselhi, Nelson Cruz Soares, Naveed Ahmed Khan (2021-12-13; ; similar):

Crocodiles are flourishing large-bodied ectotherms in a world dominated by endotherms. They survived the Cretaceous extinction event, that eradicated the dinosaurs who are thought to be their ancestral hosts. Crocodiles reside in polluted environments; and often inhabit water which contains heavy metals; frequent exposure to radiation; feed on rotten meat and considered as one of the hardy species that has successfully survived on this planet for millions of years. Another capability that crocodiles possess is their longevity. Crocodiles live much longer than similar-sized land mammals, sometimes living up to 100 years. But how do they withstand such harsh conditions that are detrimental to Homo sapiens?

Given the importance of gut microbiome on its’ host physiology, we postulate that the crocodile gut microbiome and/​or its’ metabolites produce substances contributing to their “hardiness” and longevity. Thus, we accomplished literature search in PubMed⁠, Web of Science and Google Scholar and herein, we discuss the composition of the crocodile gut microbiome, longevity and cellular senescence in crocodiles, their resistance to infectious diseases and cancer, and our current knowledge of the genome and epigenome of these remarkable species. Furthermore, preliminary studies that demonstrate the remarkable properties of crocodile gut microbial flora are discussed.

Given the profound role of the gut microbiome in the health of its’ host, it is likely that the crocodile gut microbiome and its’ metabolites may be contributing to their extended life expectancy and elucidating the underlying mechanisms and properties of these metabolites may hold clues to developing new treatments for age-related diseases for the benefit of Homo sapiens.

[Keywords: crocodiles, gut microbiome, longevity, novel metabolites, senescence, anti-cancer, infectious diseases, drug discovery]

“Temporal Variability in Quantitative Human Gut Microbiome Profiles and Implications for Clinical Research”, Vandeputte et al 2021

“Temporal variability in quantitative human gut microbiome profiles and implications for clinical research”⁠, Doris Vandeputte, Lindsey De Commer, Raul Y. Tito, Gunter Kathagen, João Sabino, Séverine Vermeire, Karoline Faust et al (2021-11-28; similar):

While clinical gut microbiota research is ever-expanding, extending reference knowledge of healthy between-subject and within-subject gut microbiota variation and its drivers remains essential; in particular, temporal variability is under-explored, and a comparison with cross-sectional variation is missing.

Here, we perform daily quantitative microbiome profiling on 713 fecal samples from 20 Belgian women over 6 weeks, combined with extensive anthropometric measurements, blood panels, dietary data, and stool characteristics.

We show substantial temporal variation for most major gut genera; we find that for 78% of microbial genera, day-to-day absolute abundance variation is substantially larger within than between individuals, with up to 100× shifts over the study period. Diversity, and especially evenness indicators also fluctuate substantially. Relative abundance profiles show similar but less pronounced temporal variation. Stool moisture, and to a lesser extent diet, are the only statistically-significant host covariates of temporal microbiota variation, while menstrual cycle parameters did not show statistically-significant effects. We find that the dysbiotic Bact2 enterotype shows increased between-subject and within-subject compositional variability.

Our results suggest that to increase diagnostic as well as target discovery power, studies could adopt a repeated measurement design and/​or focus analysis on community-wide microbiome descriptors and indices.

…How many should you collect? Most is gained in the first few samples. Collecting 3 longitudinal samples would allow calculating equilibrium abundances with substantially higher accuracy, as well as estimating temporal variation with a minimum number of samples. It does not matter when you take these samples in a 36-day time interval. Our data indicates fecal microbial communities differ as much from baseline after a day, as they do after one week or one month. While we found substantial variation in bacterial abundance, the collection of bacteria that each person carried did not change much over time. Yet, as expected, whole-community dissimilarity remains generally larger between than within individuals…This observation suggests a dynamic component to the so-called ‘Anna Karenina principle’, which states that dysbiotic communities (Bact2) tend to vary more strongly than non-dysbiotic communities. Consequently, repeated measurements are likely even more important to estimate equilibrium abundances in disease cohorts.

“Why Did the Bee Eat the Chicken? Symbiont Gain, Loss, and Retention in the Vulture Bee Microbiome”, Figueroa et al 2021

“Why Did the Bee Eat the Chicken? Symbiont Gain, Loss, and Retention in the Vulture Bee Microbiome”⁠, Laura L. Figueroa, Jessica J. Maccaro, Erin Krichilsky, Douglas Yanega, Quinn S. McFrederick (2021-11-23; ⁠, ; similar):

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 and nectar.

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 switches.

“Autism-related Dietary Preferences Mediate Autism-gut Microbiome Associations”, Yap et al 2021

2021-yap.pdf: “Autism-related dietary preferences mediate autism-gut microbiome associations”⁠, Chloe X. Yap, Anjali K. Henders, Gail A. Alvares, David L. A. Wood, Lutz Krause, Gene W. Tyson, Restuadi Restuadi et al (2021-11-11; ⁠, ; backlinks; similar):

  • Limited autism-microbiome associations from stool metagenomics of n = 247 children
  • 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 consistency.

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 ASD.

[Keywords: autism spectrum disorder, autism, gut microbiome, restricted and repetitive behaviors and interests, diet, metagenomics, stool consistency, brain-gut-microbiome axis]

“Genetic Innovations in Animal-microbe Symbioses”, Perreau & Moran 2021

2021-perreau.pdf: “Genetic innovations in animal-microbe symbioses”⁠, Julie Perreau, Nancy A. Moran (2021-08-13; ; similar):

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 partnerships.

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.

“Black Tea Quality Is Highly Affected during Processing by Its Leaf Surface Microbiome”, Tong et al 2021

2021-tong.pdf: “Black Tea Quality is Highly Affected during Processing by its Leaf Surface Microbiome”⁠, Wei Tong, Jie Yu, Qiong Wu, Lizhen Hu, Dina Tabys, Yijun Wang, Chaoling Wei, Tiejun Ling, Mallano Ali Inayat et al (2021-06-21; ; similar):

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 structure.

Tea leaves were found to mostly harbor Proteobacteria⁠, Bacteroidetes⁠, Firmicutes⁠, and Actinobacteria among bacteria and Ascomycetes among fungi. During processing, tea microbial populations changed especially between sterilized and unsterilized samples. The surface sterilization of fresh leaves before processing can remove many microbes, especially the bacteria of the genera Sphingomonas and Methylobacteria⁠, indicating that these are mostly phylloplane microbes on tea leaves. The surface sterilization removed most fungi, except the Debaryomyces⁠.

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.

[Keywords: tea quality, microbial community, tea processing, black tea, surface sterilization]

Figure 3: Black and green tea microbiome compositions described at the level of genus. (A) Bacterial composition of routine and sterilized samples. (B) Relative abundance of bacteria in all the black and green tea samples from the processing steps. (C) Relative abundance of fungi between routine and sterilized groups. (D) Sample-wise relative abundances of fungi from the different processing steps. Fresh, fresh leaves before processing; Green, samples of green tea; Routine, routine processing samples of black tea; Sterilized, samples of black tea after leaf surface sterilization.

“Kin Selection Explains the Evolution of Cooperation in the Gut Microbiota”, Simonet & McNally 2021

“Kin selection explains the evolution of cooperation in the gut microbiota”⁠, Camille Simonet, Luke McNally (2021-02-09; ; similar):

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 an 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.

[Keywords: cooperation, comparative analysis, microbiome, evolutionary microbiology]

“The Diversity and Function of Sourdough Starter Microbiomes”, Landis et al 2021

“The diversity and function of sourdough starter microbiomes”⁠, Elizabeth A. Landis, Angela M. Oliverio, Erin A. McKenney, Lauren M. Nichols, Nicole Kfoury, Megan Biango-Daniels et al (2021-01-26; similar):

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 continents.

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.

“Microbiome Connections With Host Metabolism and Habitual Diet from 1,098 Deeply Phenotyped Individuals”, Asnicar et al 2021

2021-asnicar.pdf: “Microbiome connections with host metabolism and habitual diet from 1,098 deeply phenotyped individuals”⁠, Francesco Asnicar, Sarah E. Berry, Ana M. Valdes, Long H. Nguyen, Gianmarco Piccinno, David A. Drew, Emily Leeming et al (2021-01-11; ⁠, ; similar):

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.

“Faecal Microbiota Transplant from Aged Donor Mice Affects Spatial Learning and Memory via Modulating Hippocampal Synaptic Plasticity-related and Neurotransmission-related Proteins in Young Recipients”, D’Amato et al 2020

“Faecal microbiota transplant from aged donor mice affects spatial learning and memory via modulating hippocampal synaptic plasticity-related and neurotransmission-related proteins in young recipients”⁠, Alfonsina D’Amato, Lorenzo Di Cesare Mannelli, Elena Lucarini, Angela L. Man, Gwenaelle Le Gall, Jacopo J. V. Branca et al (2020-10-01; similar):

Background: The gut-brain axis and the intestinal microbiota are emerging as key players in health and disease. Shifts in intestinal microbiota composition affect a variety of systems; however, evidence of their direct impact on cognitive functions is still lacking. We tested whether faecal microbiota transplant (FMT) from aged donor mice into young adult recipients altered the hippocampus⁠, an area of the central nervous system (CNS) known to be affected by the ageing process and related functions.

Results: Young adult mice were transplanted with the microbiota from either aged or age-matched donor mice. Following transplantation, characterization of the microbiotas and metabolomics profiles along with a battery of cognitive and behavioural tests were performed. Label-free quantitative proteomics was employed to monitor protein expression in the hippocampus of the recipients. We report that FMT from aged donors led to impaired spatial learning and memory in young adult recipients, whereas anxiety, explorative behaviour and locomotor activity remained unaffected. This was paralleled by altered expression of proteins involved in synaptic plasticity and neurotransmission in the hippocampus. Also, a strong reduction of bacteria associated with short-chain fatty acids (SCFAs) production (Lachnospiraceae⁠, Faecalibaculum⁠, and Ruminococcaceae) and disorders of the CNS (Prevotellaceae and Ruminococcaceae) was observed. Finally, the detrimental effect of FMT from aged donors on the CNS was confirmed by the observation that microglia cells of the hippocampus fimbria, acquired an ageing-like phenotype; on the contrary, gut permeability and levels of systemic and local (hippocampus) cytokines were not affected.

Conclusion: These results demonstrate that age-associated shifts of the microbiota have an impact on protein expression and key functions of the CNS. Furthermore, these results highlight the paramount importance of the gut-brain axis in ageing and provide a strong rationale to devise therapies aiming to restore a young-like microbiota to improve cognitive functions and the declining quality of life in the elderly.

“Human Postprandial Responses to Food and Potential for Precision Nutrition”, Berry et al 2020

2020-berry.pdf: “Human postprandial responses to food and potential for precision nutrition”⁠, Sarah E. Berry, Ana M. Valdes, David A. Drew, Francesco Asnicar, Mohsen Mazidi, Jonathan Wolf, Joan Capdevila et al (2020-06-11; ; similar):

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 NCT03479866.

…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).

“A Look Back at 2019: Progress Towards the Treatment of Aging As a Medical Condition”, Reason 2019

“A Look Back at 2019: Progress Towards the Treatment of Aging as a Medical Condition”⁠, Reason (2019-12-31; ; similar):

[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.

“The Interplay between Host Genetics and the Gut Microbiome Reveals Common and Distinct Microbiome Features for Human Complex Diseases”, Xu et al 2019

“The interplay between host genetics and the gut microbiome reveals common and distinct microbiome features for human complex diseases”⁠, Fengzhe Xu, Yuanqing Fu, Ting-yu Sun, Zengliang Jiang, Zelei Miao, Menglei Shuai, Wanglong Gou, Chu-wen Ling et al (2019-12-26; similar):

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 Mendelian 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.

“A 5700 Year-old Human Genome and Oral Microbiome from Chewed Birch Pitch”, Jensen et al 2019

“A 5700 year-old human genome and oral microbiome from chewed birch pitch”⁠, Theis Z. T. Jensen, Jonas Niemann, Katrine Højholt Iversen, Anna K. Fotakis, Shyam Gopalakrishnan, Åshild J. Vågene et al (2019-12-17; backlinks; similar):

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 Tract Microbiome in Older Women Exhibits Host Genetics and Environmental Influences”, Adebayo et al 2019

“The urinary tract microbiome in older women exhibits host genetics and environmental influences”⁠, AS Adebayo, G. Ackermann, R. C. Bowyer, P. Wells, G. Humphreys, R. Knight, T. D. Spector, C. J. Steves et al (2019-11-12; similar):

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's Unholy Trinity: Dysregulated Stress, Immunity, and the Microbiome”, Pereira et al 2019

2019-pereira.pdf: “Depression's Unholy Trinity: Dysregulated Stress, Immunity, and the Microbiome”⁠, Joana da Cruz Pereira, Kieran Rea, Yvonne M. Nolan, Olivia F. O’Leary, Timothy G. Dinan, John F. Cryan et al (2019-09-30; ⁠, ; similar):

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.

“Long-term Dietary Intervention Reveals Resilience of the Gut Microbiota despite Changes in Diet and Weight”, Fragiadakis et al 2019

“Long-term dietary intervention reveals resilience of the gut microbiota despite changes in diet and weight”⁠, Gabriela K. Fragiadakis, Hannah C. Wastyk, Jennifer L. Robinson, Erica D. Sonnenburg, Justin L. Sonnenburg et al (2019-08-08; similar):

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.

“The Neuroactive Potential of the Human Gut Microbiota in Quality of Life and Depression”, Valles-Colomer et al 2019

2019-vallescolomer.pdf: “The neuroactive potential of the human gut microbiota in quality of life and depression”⁠, Mireia Valles-Colomer, Gwen Falony, Youssef Darzi, Ettje F. Tigchelaar, Jun Wang, Raul Y. Tito, Carmen Schiweck et al (2019-01-01; )

“Supplementation With Akkermansia Muciniphila in Overweight and Obese Human Volunteers: a Proof-of-concept Exploratory Study”, Depommier et al 2019

2019-depommier.pdf: “Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study”⁠, Clara Depommier, Amandine Everard, Camp#x000E9;line Druart, Hubert Plovier, Matthias Van Hul, Sara Vieira-Silva et al (2019-01-01; )

“Bacterial Variability in the Mammalian Gut Captured by a Single-cell Synthetic Oscillator”, Riglar et al 2019

“Bacterial variability in the mammalian gut captured by a single-cell synthetic oscillator”⁠, David T. Riglar, David L. Richmond, Laurent Potvin-Trottier, Andrew A. Verdegaal, Alexander D. Naydich et al (2019; similar):

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.

“Gut Microbiome Response to a Modern Paleolithic Diet in a Western Lifestyle Context”, Barone et al 2018

“Gut microbiome response to a modern Paleolithic diet in a Western lifestyle context”⁠, M Barone, S. Turroni, S. Rampelli, M. Soverini, F. D’Amico, E. Biagi, P. Brigidi, E. Troiani, M. Candela et al (2018-12-13; similar):

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 high consumption 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.

“Biological and Cultural Drivers of Oral Microbiota in Medieval and Post-Medieval London, UK”, Farrer et al 2018

“Biological and cultural drivers of oral microbiota in Medieval and Post-Medieval London, UK”⁠, A. G. Farrer, J. Bekvalac, R. Redfern, N. Gully, K. Dobney, A. Cooper, L. S. Weyrich (2018-06-11; similar):

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.

“Anti-aging Food That Improves Markers of Health in Senior Dogs by Modulating Gut Microbiota and Metabolite Profiles”, Gebreselassie et al 2018

“Anti-aging food that improves markers of health in senior dogs by modulating gut microbiota and metabolite profiles”⁠, Eden Ephraim Gebreselassie, Matthew I. Jackson, Maha Yerramilli, Dennis E. Jewell (2018-05-16; similar):

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.

“Dynamic Linear Models Guide Design and Analysis of Microbiota Studies within Artificial Human Guts”, Silverman et al 2018

“Dynamic linear models guide design and analysis of microbiota studies within artificial human guts”⁠, Justin D. Silverman, Heather Durand, Rachael J. Bloom, Sayan Mukherjee, Lawrence A. David (2018-04-24; similar):

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.

“Parkinson’s Disease and Bacteriophages As Its Overlooked Contributors”, Tetz et al 2018

“Parkinson’s disease and bacteriophages as its overlooked contributors”⁠, George Tetz, Stuart M. Brown, Yuhan Hao, Victor Tetz (2018-04-22; similar):

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.

“Effects of Exclusive Breastfeeding on Infant Gut Microbiota: a Meta-analysis across Studies and Populations”, Ho et al 2018

“Effects of exclusive breastfeeding on infant gut microbiota: a meta-analysis across studies and populations”⁠, Nhan T. Ho, Fan Li, Kathleen A. Lee-Sarwar, Hein M. Tun, Bryan Brown, Pia S. Pannaraj, Lianna F. Wood et al (2018-03-31; similar):

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 pathways associated with non-EBF was larger in infants delivered by C-section than delivered vaginally. Longer duration of EBF mitigated diarrhea-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.

“The Drosophila Microbiome Has a Limited Influence on Sleep, Activity, and Courtship Behaviors”, Selkrig et al 2018

“The Drosophila microbiome has a limited influence on sleep, activity, and courtship behaviors”⁠, Joel Selkrig, Farhan Mohammad, Soon Hwee Ng, Chua Jia Yi, Tayfun Tumkaya, Joses Ho, Yin Ning Chiang, Dirk Rieger et al (2018-03-22; similar):

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.

“Gut Microbiome Transition across a Lifestyle Gradient in Himalaya”, Jha et al 2018

“Gut microbiome transition across a lifestyle gradient in Himalaya”⁠, Aashish R. Jha, Emily R. Davenport, Yoshina Gautam, Dinesh Bhandari, Sarmila Tandukar, Katharine Ng, Susan Holmes et al (2018-01-27; similar):

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 semi-nomadic 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.

“An Interventional Soylent Diet Increases the Bacteroidetes to Firmicutes Ratio in Human Gut Microbiome Communities: a Randomized Controlled Trial”, Hsu et al 2017

“An interventional Soylent diet increases the Bacteroidetes to Firmicutes ratio in human gut microbiome communities: a randomized controlled trial”⁠, Ryan H. Hsu, Dylan M. McCormick, Mitchell J. Seitz, Lauren M. Lui, Harneet S. Rishi, Adam P. Arkin (2017-10-13; similar):

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: (1) a regular diet for 2 days, (2) a Soylent-only diet (five servings of Soylent daily and water as needed) for 4 days, and (3) 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.

“Environmental Factors Dominate over Host Genetics in Shaping Human Gut Microbiota Composition”, Rothschild et al 2017

“Environmental factors dominate over host genetics in shaping human gut microbiota composition”⁠, Daphna Rothschild, Omer Weissbrod, Elad Barkan, Tal Korem, David Zeevi, Paul I. Costea, Anastasia Godneva et al (2017-06-16; similar):

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, waist circumference, 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.

“Commensal Bacteria and Essential Amino Acids Control Food Choice Behavior and Reproduction”, Leitão-Gonçalves et al 2017

“Commensal bacteria and essential amino acids control food choice behavior and reproduction”⁠, Ricardo Leitão-Gonçalves, Zita Carvalho-Santos, Ana Patrícia Francisco, Gabriela Tondolo Fioreze, Margarida Anjos et al (2017-03-15; similar):

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.

Author summary:

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.

“Intermittent Fasting Promotes White Adipose Browning and Decreases Obesity by Shaping the Gut Microbiota”, Li et al 2017

2017-li.pdf: “Intermittent Fasting Promotes White Adipose Browning and Decreases Obesity by Shaping the Gut Microbiota”⁠, Guolin Li, Cen Xie, Siyu Lu, Robert G. Nichols, Yuan Tian, Licen Li, Daxeshkumar Patel, Yinyan Ma, Chad N. Brocker et al (2017-01-01; )

“Transient Rapamycin Treatment Can Increase Lifespan and Healthspan in Middle-aged Mice”, Bitto et al 2016

“Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice”⁠, Alessandro Bitto, Takashi K. Ito, Victor V. Pineda, Nicolas J. LeTexier, Heather Z. Huang, Elissa Sutlief et al (2016-08-23; ; backlinks; similar):

The FDA approved drug rapamycin 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 healthy aging.

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.

“Is Eating Behavior Manipulated by the Gastrointestinal Microbiota? Evolutionary Pressures and Potential Mechanisms”, Alcock et al 2014

“Is eating behavior manipulated by the gastrointestinal microbiota? Evolutionary pressures and potential mechanisms”⁠, Joe Alcock, Carlo C. Maley, C. Athena Aktipis (2014; ; similar):

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 manipulable 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”, Goodrich et al 2014

“Human genetics shape the gut microbiome”⁠, Julia K. Goodrich, Jillian L. Waters, Angela C. Poole, Jessica L. Sutter, Omry Koren, Ran Blekhman, Michelle Beaumont et al (2014; similar):

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.

“Sequence-specific Antimicrobials Using Efficiently Delivered RNA-guided Nucleases”, Citorik et al 2014

“Sequence-specific antimicrobials using efficiently delivered RNA-guided nucleases”⁠, Robert J. Citorik, Mark Mimee, Timothy K. Lu (2014; ; backlinks; similar):

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 DNA targets 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 in a 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.

UBiome

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Microbiome

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Kimchi

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Human microbiota

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Gut-brain axis

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Germ-free animal

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Butyric acid

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Breastfeeding

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Miscellaneous