Localized microbially induced inflammation influences distant healthy tissues in the human oral cavity.

Variation in human immune response to the same bacterial or viral pathogen is well established in the literature. Variation in immune response to microbial challenge has also been observed within the human oral cavity. Our recent study focused on characterizing observed variations in microbially induced gingival inflammation-resulting in three distinct clinical Inflammatory Responder Types (IRTs): High-IRT, Low-IRT, and Slow-IRT. Here, we applied a high-resolution temporal multiomic analysis during microbially induced inflammation in order to characterize the effects of localized oral inflammation on distant healthy tissues in young healthy adults. Our results highlight a nonlocalized subclinical effect with alterations in proinflammatory host mediators and an ecological shift toward dysbiosis within the subgingival microbiome in an IRT-dependent manner-despite maintained oral hygiene. Our results provide mechanistic insight into how healthy tissues within humans are influenced by distant localized inflammation and may ultimately become susceptible to disease.

Transcriptome of Epibiont Saccharibacteria Nanosynbacter lyticus Strain TM7x During the Establishment of Symbiosis.

Saccharibacteria Nanosynbacter lyticus strain TM7x is a member of the broadly distributed candidate phylum radiation. These bacteria have ultrasmall cell sizes, have reduced genomes, and live as epibionts on the surfaces of other bacteria. The mechanisms by which they establish and maintain this relationship are not yet fully understood. The transcriptomes of the epibiont TM7x and its host bacteria Schaalia odontolytica strain XH001 were captured across the establishment of symbiosis during both the initial interaction and stable symbiosis. The results showed a dynamic interaction with large shifts in gene expression for both species between the initial encounter and stable symbiosis, notably in transporter genes. During stable symbiosis, the host XH001 showed higher gene expression for peptidoglycan biosynthesis, mannosylation, cell cycle and stress-related genes, whereas it showed lower expression of chromosomal partitioning genes. This was consistent with the elongated cell shape seen in XH001 infected with TM7x and our discovery that infection resulted in thickened cell walls. Within TM7x, increased pili, type IV effector genes, and arginine catabolism/biosynthesis gene expression during stable symbiosis implied a key role for these functions in the interaction. Consistent with its survival and persistence in the human microbiome as an obligate epibiont with reduced de novo biosynthetic capacities, TM7x also showed higher levels of energy production and peptidoglycan biosynthesis, but lower expression of stress-related genes, during stable symbiosis. These results imply that TM7x and its host bacteria keep a delicate balance in order to sustain an episymbiotic lifestyle. IMPORTANCE Nanosynbacter lyticus type strain TM7x is the first cultivated member of the Saccharibacteria and the candidate phyla radiation (CPR). It was discovered to be ultrasmall in cell size with a highly reduced genome that establishes an obligate epibiotic relationship with its host bacterium. The CPR is a large, monophyletic radiation of bacteria with reduced genomes that includes Saccharibacteria. The vast majority of the CPR have yet to be cultivated, and our insights into these unique organisms to date have been derived from only a few Saccharibacteria species. Being obligate parasites, it is unknown how these ultrasmall Saccharibacteria, which are missing many de novo biosynthetic pathways, are maintained at a high prevalence within the human microbiome as well as in the environment.

Klebsiella and Providencia emerge as lone survivors following long-term starvation of oral microbiota.

It is well-understood that many bacteria have evolved to survive catastrophic events using a variety of mechanisms, which include expression of stress-response genes, quiescence, necrotrophy, and metabolic advantages obtained through mutation. However, the dynamics of individuals leveraging these abilities to gain a competitive advantage in an ecologically complex setting remain unstudied. In this study, we observed the saliva microbiome throughout the ecological perturbation of long-term starvation, allowing only the species best equipped to access and use the limited resources to survive. During the first several days, the community underwent a death phase that resulted in a ∼50-100-fold reduction in the number of viable cells. Interestingly, after this death phase, only three species, Klebsiella pneumoniae, Klebsiella oxytoca, and Providencia alcalifaciens, all members of the family Enterobacteriaceae, appeared to be transcriptionally active and recoverable. Klebsiella are significant human pathogens, frequently resistant to multiple antibiotics, and recently, ectopic colonization of the gut by oral Klebsiella was documented to induce dysbiosis and inflammation. MetaOmics analyses provided several leads for further investigation regarding the ecological success of the Enterobacteriaceae. The isolates accumulated single nucleotide polymorphisms in known growth advantage in stationary phase alleles and produced natural products closely resembling antimicrobial cyclic depsipeptides. The results presented in this study suggest that pathogenic Enterobacteriaceae persist much longer than their more benign neighbors in the salivary microbiome when faced with starvation. This is particularly significant, given that hospital surfaces contaminated with oral fluids, especially sinks and drains, are well-established sources of outbreaks of drug-resistant Enterobacteriaceae.

Microplastic Abundance and Composition in Western Lake Superior As Determined via Microscopy, Pyr-GC/MS, and FTIR.

While plastic pollution in marine and freshwater systems is an active area of research, there is not yet an in-depth understanding of the distributions, chemical compositions, and fates of plastics in aquatic environments. In this study, the magnitude, distribution, and common polymers of microplastic pollution in surface waters in western Lake Superior are determined. Analytical methodology, including estimates of ambient contamination during sample collection and processing, are described and employed. Microscopy, pyrolysis-gas chromatography/mass spectrometry (Pyr-GC/MS), and Fourier transform infrared spectroscopy (FTIR) were used to quantify and identify microplastic particles. In surface waters, fibers were the most frequently observed morphology, and, based upon PyGC/MS analysis,  polyvinyl chloride was the most frequently observed polymer, followed by polypropylene and polyethylene. The most common polymer identified by FTIR was polyethylene. Despite the low human population in Lake Superior's watershed, microplastic particles (particularly fibers, fragments, and films) were identified in western-lake surface waters at levels comparable to average values reported in studies within Lake Michigan, the North Atlantic Ocean, and the South Pacific Ocean. This study provides insight into the magnitude of microplastic pollution in western Lake Superior, and describes in detail methodology to improve future microplastics studies in aquatic systems.

Tobacco control in California compared with the rest of the USA: trends in adult per capita cigarette consumption.

BACKGROUND: In the 1990s, California led the USA in state-level tobacco control strategies. However, after 2000, California lost ground on cigarette taxes, although it maintained higher levels of smoke-free homes among smokers. METHODS: Trends in per capita cigarette consumption were assessed through taxed sales data and from self-report in repeated national cross-sectional surveys. Linear regressions identified changes in trends after year 2000 separately for California and the rest of the USA. Using data from each state, a linear regression tested the association between different tobacco control strategies and per capita consumption. Change in self-reported per capita consumption was partitioned into contributions associated with initiation, quitting and reduction in cigarette consumption level. RESULTS: Both taxed cigarette sales and per capita consumption declined rapidly in the USA from 1985 to 2015. Declines were particularly fast in California before 2000 but slowed thereafter. In 2014, per capita consumption in California was 29.4 packs/adult/year, but 90% higher in the rest of the USA. Modelling state-level data, every $1 increase in cigarette taxes reduced consumption by 4.8 (95% CI 2.9 to 6.8) packs/adult/year. Every 5% increase in the proportion of smokers with smoke-free homes reduced consumption by 8.0 (95% CI 7.0 to 8.9) packs/adult/year. The different patterns in California and the rest of the USA are at least partially explained by these two variables. The slow down in per capita consumption in California can be attributed to changes in initiation, quitting and especially smokers reducing their consumption level. CONCLUSIONS: Tobacco control strategies need to be continually updated to maintain momentum towards a smoke-free society.

Ultrasmall epibiont Nanosynbacter lyticus strain TM7x and host bacteria transcriptional activity after initial host parasitism.

Background: Oral Saccharibacteria Nanosynbacter lyticus strain TM7× lives as an ultrasmall epibiont on the surface of its host, Schaalia odontolytica strain XH001. Establishing this interaction is a poorly understood multi-step process. The recovery phase marks a shift in the TM7×/host interaction, switching from the early killing phase, with extensive host cell death, to a stable symbiosis phase where the host and epibiont can grow together. Results: Transcriptomes of TM7× and host, XH001, were captured during the recovery phase and compared to uninfected host and the early host/epibiont interaction (initial encounter). XH001 showed increased expression for rhamnose cell wall components and for the precursor to peptidoglycan while TM7× showed increases in the peptidoglycan pathway. Transporter expression was generally increased for both organisms during recovery compared to the initial encounter, though, XH001 showed lower amino acid transporter expression. Consistent with host parasitism, XH001 showed increased expression of various stress-related genes during recovery while TM7× showed reduced stress. TM7× displayed higher expression of type IV pili, consistent with increased attachment to new hosts. Conclusion: As TM7× is a member of the broadly distributed Candidate Phyla Radiation with small genomes lacking numerous biosynthetic pathways, this study provides further insights into how these epibionts interact and modulate their host bacteria.

Identifying essential genes in Schaalia odontolytica using a highly-saturated transposon library.

The unique epibiotic-parasitic relationship between Nanosynbacter lyticus type strain TM7x, a member of the newly identified Candidate Phyla Radiation, now referred to as Patescibacteria, and its basibiont, Schaalia odontolytica strain XH001 (formerly Actinomyces odontolyticus), require more powerful genetic tools for deeper understanding of the genetic underpinnings that mediate their obligate relationship. Previous studies have mainly characterized the genomic landscape of XH001 during or post TM7x infection through comparative genomic or transcriptomic analyses followed by phenotypic analysis. Comprehensive genetic dissection of the pair is currently cumbersome due to the lack of robust genetic tools in TM7x. However, basic genetic tools are available for XH001 and this study expands the current genetic toolset by developing high-throughput transposon insertion sequencing (Tn-seq). Tn-seq was employed to screen for essential genes in XH001 under laboratory conditions. A highly saturated Tn-seq library was generated with nearly 660,000 unique insertion mutations, averaging one insertion every 2-3 nucleotides. 203 genes, 10.5% of the XH001 genome, were identified as putatively essential.

Specific host metabolite and gut microbiome alterations are associated with bone loss during spaceflight.

Understanding the axis of the human microbiome and physiological homeostasis is an essential task in managing deep-space-travel-associated health risks. The NASA-led Rodent Research 5 mission enabled an ancillary investigation of the gut microbiome, varying exposure to microgravity (flight) relative to ground controls in the context of previously shown bone mineral density (BMD) loss that was observed in these flight groups. We demonstrate elevated abundance of Lactobacillus murinus and Dorea sp. during microgravity exposure relative to ground control through whole-genome sequencing and 16S rRNA analyses. Specific functionally assigned gene clusters of L. murinus and Dorea sp. capable of producing metabolites, lactic acid, leucine/isoleucine, and glutathione are enriched. These metabolites are elevated in the microgravity-exposed host serum as shown by liquid chromatography-tandem mass spectrometry (LC-MS/MS) metabolomic analysis. Along with BMD loss, ELISA reveals increases in osteocalcin and reductions in tartrate-resistant acid phosphatase 5b signifying additional loss of bone homeostasis in flight.

Insights into the virulence of oral biofilms: discoveries from proteomics.

This review covers developments in the study of polymicrobial communities, biofilms and selected areas of host response relevant to dental plaque and related areas of oral biology. The emphasis is on recent studies in which proteomic methods, particularly those using mass spectrometry as a readout, have played a major role in the investigation. The last 5-10 years have seen a transition of such methods from the periphery of oral biology to the mainstream, as in other areas of biomedical science. For reasons of focus and space, the authors do not discuss biomarker studies relevant to improved diagnostics for oral health, as this literature is rather substantial in its own right and deserves a separate treatment. Here, global gene regulation studies of plaque-component organisms, biofilm formation, multispecies interactions and host-microbe interactions are discussed. Several aspects of proteomics methodology that are relevant to the studies of multispecies systems are commented upon.

Proteomics of Streptococcus gordonii within a model developing oral microbial community.

BACKGROUND: Streptococcus gordonii is one of several species that can initiate the formation of oral biofilms that develop into the complex multispecies microbial communities referred to as dental plaque. It is in the context of dental plaque that periodontal pathogens such as Porphyromonas gingivalis cause disease. We have previously reported a whole cell quantitative proteomics investigation of P. gingivalis in a model dental plaque community of S. gordonii, P. gingivalis, and Fusobacterium nucleatum. Here we report the adaptation of S. gordonii to the same model. RESULTS: 1122 S. gordonii proteins were detected in S. gordonii control samples, 915 in communities with F. nucleatum, 849 with P. gingivalis, and 649 with all three organisms. Quantitative comparisons showed extensive proteome changes in association with F. nucleatum or P. gingivalis individually or both P. gingivalis and F. nucleatum together. The changes were species specific, though the P. gingivalis interaction may be dominant, indicated by large differences between the proteomes with F. nucleatum or P. gingivalis but limited changes between communities with P. gingivalis or both P. gingivalis and F. nucleatum. The results were inspected manually and an ontology analysis conducted using DAVID. Extensive changes were seen in nutrition pathways with increases in energy metabolism and changes in the resulting byproducts, while the acid and sugar repressed PTS (phosphoenolpyruvate dependent phosphotransferase system) sugar transport systems showed decreases. These results were seen across all the multispecies samples, though with different profiles according to the partner species. F. nucleatum association decreased proteins for the metabolic end products acetate and ethanol but increased lactate, the primary source of acidity from streptococcal cultures. P. gingivalis containing samples had a reduction in levels of proteins for ethanol and formate but increased proteins for both acetate and lactate production. The communities also showed increases in exopolysaccharide synthesis, amino acid biosynthesis, and oxidative stress protection and decreases in adhesion and transporter proteins. CONCLUSION: This study showed that S. gordonii demonstrates species specific responses during interactions with F. nucleatum or P. gingivalis. Extensive changes were seen in energy metabolism and byproduct production implicating nutrient transfer as an important community interaction.

Public interest in ∆8-Tetrahydrocannabinol (delta-8-THC) increased in US states that restricted ∆9-Tetrahydrocannabinol (delta-9-THC) use.

BACKGROUND: There is an expanding unregulated market for a psychotropic compound called ∆8-Tetrahydrocannabinol (delta-8-THC) that is being derived from hemp, but there are no empirical estimates of public interest in this compound. METHODS: To measure public interest, we obtained yearly Google query fractions (QFs) that mentioned delta-8-THC (i.e., "delta 8," "delta-8," or "Δ8") for the past decade (from January 2011 through August 2021) for every country and territory in the world and every state in the United States (US) from Google Trends. We also obtained the same trends for the last complete month of data for all US states (July 2021) to compare across cannabis use policies. We summarized QFs across years, countries, US states and cannabis policies in US states using linear regression, means and ratios. We estimated raw search counts for the US using comscore.com. RESULTS: The global rate of delta-8-THC searches was stable between 2011 and 2019 before increasing by 257.0% from 2019 to 2020 and 705.0% from 2020 to 2021. In 2021, the rate of delta-8-THC searches in the US was at least 10 times higher than the rates in other countries or territories. In absolute terms, there were 22.3 million delta-8-THC searches in the US in the first 8 months of 2021 alone. Increases in delta-8-THC searches from 2020 to 2021 occurred in all 50 US states and the District of Columbia (Mean 854.2%; range = 256.4% - 2831.2%) but continued to vary substantially between states in 2021. In July 2021, the legal status of delta-9-THC use across US states explained 49.0% of the variance in delta-8-THC QFs between US states (R2 = 0.490; p < 0.001) and was inversely associated, where delta-8-THC QFs were higher in jurisdictions with stricter cannabis use policies. CONCLUSION: Public interest in delta-8-THC increased rapidly in 2020 and 2021 and was particularly high in US states that restricted delta-9-THC use. Jurisdictions should clarify whether delta-8-THC can be sold as a hemp product.

Strain-Level Variation and Diverse Host Bacterial Responses in Episymbiotic Saccharibacteria.

Saccharibacteria (TM7), which are obligate episymbionts growing on the surface of host bacteria, may play an important role in oral disease, such as periodontitis (1, 2). As TM7 is a newly cultured lineage of bacteria, its research is limited by the small number of isolated representatives relative to the number of TM7 genomes assembled from culture-independent studies (3-5). A comprehensive view of both TM7 taxa and TM7 strain-level variations remains opaque. In this study, we expanded our previously developed TM7 baiting method into using many host bacteria in parallel, which allowed us to obtain 37 TM7 strains from the human oral cavity. These strains were further classified into low-enrichment (LE, n = 24) and high-enrichment (HE, n = 13) groups based on their proficiency at propagating on host bacteria. Of the 13 HE strains, 10 belong to "Candidatus Nanosynbacter sp." strain HMT-352 (human microbial taxon) (6), enabling us to explore both the phenotypic and genomic strain variations within a single TM7 species. We show that TM7 HMT-352 strains exhibit a diverse host range and varied growth dynamics during the establishment of their episymbiotic relationship with host bacteria. Furthermore, despite HMT-352 strains sharing a majority of their genes, we identified several gene clusters that may play a pivotal role in host affinity. More importantly, our comparative analyses also provide TM7 gene candidates associated with strain-level phenotypic variation that may be important for episymbiotic interactions with host bacteria. IMPORTANCE Candidate phylum radiation (CPR) bacteria comprise a poorly understood phylum that is estimated to encompass ∼26% of all diversity of domain bacteria. Among CPR bacteria, the Saccharibacteria lineage (TM7) is of particular interest, as it is found in high abundance in the mammal microbiome and has been associated with oral disease. While many CPR genomes, TM7 included, have been acquired through culture-independent methods, only a small number of representatives have been isolated. Such isolated representatives, however, shed light on the physiology, pathogenesis, and episymbiotic interactions of TM7. Combined with genomic analyses, experiments involving isolated representatives can distinguish phylogenetic to phenotypic discrepancies and better identify genes of importance. In this study, we utilized multiple host bacteria in parallel to isolate TM7 bacteria and examined strain-level variation in TM7 to reveal key genes that may drive TM7-host interactions. Our findings accentuate that broad phylogenetic characterization of CPR is the next step in understanding these bacteria.

Draft Genome Sequences of Nine "Candidatus Nanosynbacter sp. HMT-352" Strains Cultured from the Human Oral Cavity.

Here, we report draft genome sequences for nine strains of "Candidatus Nanosynbacter sp. HMT-352." These strains and their sequences were used to interrogate strain-level variations in host range, gene content, and growth dynamics among the phylum "Candidatus Saccharibacteria."

An integrated proteomics/transcriptomics approach points to oxygen as the main electron sink for methanol metabolism in Methylotenera mobilis.

Methylotenera species, unlike their close relatives in the genera Methylophilus, Methylobacillus, and Methylovorus, neither exhibit the activity of methanol dehydrogenase nor possess mxaFI genes encoding this enzyme, yet they are able to grow on methanol. In this work, we integrated a genome-wide proteomics approach, shotgun proteomics, and a genome-wide transcriptomics approach, shotgun transcriptome sequencing (RNA-seq), of Methylotenera mobilis JLW8 to identify genes and enzymes potentially involved in methanol oxidation, with special attention to alternative nitrogen sources, to address the question of whether nitrate could play a role as an electron acceptor in place of oxygen. Both proteomics and transcriptomics identified a limited number of genes and enzymes specifically responding to methanol. This set includes genes involved in oxidative stress response systems, a number of oxidoreductases, including XoxF-type alcohol dehydrogenases, a type II secretion system, and proteins without a predicted function. Nitrate stimulated expression of some genes in assimilatory nitrate reduction and denitrification pathways, while ammonium downregulated some of the nitrogen metabolism genes. However, none of these genes appeared to respond to methanol, which suggests that oxygen may be the main electron sink during growth on methanol. This study identifies initial targets for future focused physiological studies, including mutant analysis, which will provide further details into this novel process.

Overlapping repressor binding sites regulate expression of the Methanococcus maripaludis glnK(1) operon.

The euryarchaeal transcriptional repressor NrpR regulates a variety of nitrogen assimilation genes by 2-oxoglutarate-reversible binding to conserved palindromic operators. The number and positioning of these operators varies among promoter regions of regulated genes, suggesting NrpR can bind in different patterns. Particularly intriguing is the contrast between the nif and glnK(1) promoter regions of Methanococcus maripaludis, where two operators are present but with different configurations. Here we study NrpR binding and regulation at the glnK(1) promoter, where the two operator sequences overlap and occur on opposite faces of the double helix. We find that both operators function in binding, with a dimer of NrpR binding simultaneously to each overlapping operator. We show in vivo that the first operator plays a primary role in regulation and the second operator plays an enhancing role. This is the first demonstration of overlapping operators functioning in Archaea.

Expressed genome of Methylobacillus flagellatus as defined through comprehensive proteomics and new insights into methylotrophy.

In recent years, techniques have been developed and perfected for high-throughput identification of proteins and their accurate partial sequencing by shotgun nano-liquid chromatography-tandem mass spectrometry (nano-LC-MS/MS), making it feasible to assess global protein expression profiles in organisms with sequenced genomes. We implemented comprehensive proteomics to assess the expressed portion of the genome of Methylobacillus flagellatus during methylotrophic growth. We detected a total of 1,671 proteins (64% of the inferred proteome), including all the predicted essential proteins. Nonrandom patterns observed with the nondetectable proteins appeared to correspond to silent genomic islands, as inferred through functional profiling and genome localization. The protein contents in methylamine- and methanol-grown cells showed a significant overlap, confirming the commonality of methylotrophic metabolism downstream of the primary oxidation reactions. The new insights into methylotrophy include detection of proteins for the N-methylglutamate methylamine oxidation pathway that appears to be auxiliary and detection of two alternative enzymes for both the 6-phosphogluconate dehydrogenase reaction (GndA and GndB) and the formate dehydrogenase reaction (FDH1 and FDH4). Mutant analysis revealed that GndA and FDH4 are crucial for the organism's fitness, while GndB and FDH1 are auxiliary.

Complete Genome Sequence of Strain BB001, a Novel Epibiont Bacterium from the Candidate Phylum Saccharibacteria (TM7).

Strain BB001 is cultivated from the human oral cavity on its basibiont bacterial host Actinomyces sp. It is an ultrasmall bacterium with a reduced genome that grows obligately on its bacterial host. BB001 is the first member of human microbiome taxon 957.

Self-reported Cannabidiol (CBD) Use for Conditions With Proven Therapies.

Importance: Use of cannabidiol (CBD) has markedly increased in the past 5 years, concurrent with marketing claims that over-the-counter CBD can be used to treat almost any health condition. However, the reasons why individuals use CBD remain unclear. Objective: To assess whether individuals are using CBD for diagnosable conditions that have evidence-based therapies. Design, Setting, and Participants: This case series assessed claimed treatment applications reported by CBD users in public testimonials shared on the Reddit forum r/CBD. The r/CBD forum was selected because it includes a large, naturally occurring sample of 104 917 registered individuals who publicly discuss their experiences using CBD. All r/CBD posts were obtained from January 1, 2014, through August 31, 2019. A random sample of posts was drawn (n = 3000) and filtered to include posts in which self-identified CBD users testified why they take CBD (n = 376). Exposures: Self-reported use of CBD for medicinal purposes. Main Outcomes and Measures: Cannabidiol testimonials were divided into 11 subcategories corresponding with the condition's medical subspecialty and 2 subcategories corresponding with wellness benefits. Posts were allowed to receive more than 1 label. Results: Of the 376 posts labeled as testimonials, 90.0% (95% CI, 86.8%-92.8%) of testimonials claimed that CBD treated the individual's diagnosable conditions. Psychiatric conditions (eg, autism or depression) were the most frequently cited subcategory, mentioned in 63.9% (95% CI, 59.0%-69.1%) of testimonials, followed by orthopedic (26.4%; 95% CI, 21.8%-31.1%), sleep (14.6%; 95% CI, 11.3%-18.5%), and neurological (6.9%; 95% CI, 4.4%-9.6%) conditions. Testimonials also claimed that CBD treated gastroenterological conditions (3.9%; 95% CI, 1.9%-6.1%), as well as addiction, cardiological, dermatological, ophthalmological, oral health, and sexual health conditions (<2.0% each). By contrast, just 29.5% (95% CI, 24.8%-34.2%) of testimonies claimed any wellness benefit, with most citing mental wellness (eg, "quieting my mind") (29.5% [95% CI, 24.2%-34.4%]); 1.4% (95% CI, 0.3%-2.8%) claimed a physical wellness benefit (eg, "exercise performance"). Conclusions and Relevance: The findings of this case series suggest a need for regulation of factors associated with CBD being used to treat diagnosable conditions, engagement of health care professionals with patients on their potential CBD use, and implementation of public health campaigns that encourage the public to seek treatment advice from health care professionals regarding evidence-based therapies.

Acquisition and Adaptation of Ultra-small Parasitic Reduced Genome Bacteria to Mammalian Hosts.

The first cultivated representative of the enigmatic phylum Saccharibacteria (formerly TM7) was isolated from humans and revealed an ultra-small cell size (200-300 nm), a reduced genome with limited biosynthetic capabilities, and a unique parasitic lifestyle. TM7x was the only cultivated member of the candidate phyla radiation (CPR), estimated to encompass 26% of the domain Bacteria. Here we report on divergent genomes from major lineages across the Saccharibacteria phylum in humans and mammals, as well as from ancient dental calculus. These lineages are present at high prevalence within hosts. Direct imaging reveals that all groups are ultra-small in size, likely feeding off commensal bacteria. Analyses suggest that multiple acquisition events in the past led to the current wide diversity, with convergent evolution of key functions allowing Saccharibacteria from the environment to adapt to mammals. Ultra-small, parasitic CPR bacteria represent a relatively unexplored paradigm of prokaryotic interactions within mammalian microbiomes.