Clostridium tanneri sp. nov., isolated from the faecal material of an alpaca.

A strictly anaerobic, Gram-stain-negative rod-shaped bacterium, designated A1-XYC3T, was isolated from the faeces of an alpaca (Lama pacos). On the basis of the results of a comparative 16S rRNA gene sequence analysis, the isolate was assigned to the genus Clostridium with the highest sequence similarities to Clostridium magnum DSM 2767T (96.8 %), Clostridium carboxidivorans P7T (96.3 %) and Clostridium aciditolerans JW/YJL-B3T (96.1 %). The average nucleotide identity between A1-XYC3T, C. magnum, C. carboxidivorans and C. aciditolerans was 77.4, 76.1 and 76.6  %, respectively. The predominant components of the cellular fatty acids of A1-XYC3T were C14 : 0, C16 : 0 and summed feature 10, containing C18:0/C17:0 cyclo. The DNA G+C content was 32.4 mol%. On the basis of biochemical, phylogenetic, genotypic and chemotaxonomic criteria, this isolate represents a novel species within Clostridium sensu stricto for which the name Clostridium tanneri sp. nov. is proposed. The type strain of this species is strain A1-XYC3T (=CCM 9376T=NRRL B-65691T).

Methylocystis suflitae sp. nov., a novel type II methanotrophic bacterium isolated from landfill cover soil.

A bacterial strain, designated NLS-7T, was isolated through enrichment of landfill cover soil in methane-oxidizing conditions. Strain NLS-7T is a Gram-stain negative, non-motile rod, approximately 0.8 µm wide by 1.3 µm long. Phylogenetic analysis based on 16S rRNA gene sequencing places it within the genus Methylocystis, with its closest relatives being M. hirsuta, M. silviterrae and M. rosea, with 99.9, 99.7 and 99.6 % sequence similarity respectively. However, average nucleotide identity and average amino acid identity values below the 95 % threshold compared to all the close relatives and digital DNA-DNA hybridization values between 20.9 and 54.1 % demonstrate that strain NLS-7T represents a novel species. Genome sequencing generated 4.31 million reads and genome assembly resulted in the generation of 244 contigs with a total assembly length of 3 820 957 bp (N50, 37 735 bp; L50, 34). Genome completeness is 99.5 % with 3.98 % contamination. It is capable of growth on methane and methanol. It grows optimally at 30 °C between pH 6.5 and 7.0. Strain NLS-7T is capable of atmospheric dinitrogen fixation and can use ammonium (as NH4Cl), l-aspartate, l-arginine, yeast extract, nitrate, l-leucine, l-proline, l-methionine, l-lysine and l-alanine as nitrogen sources. The major fatty acids are C18:1 ω8c and C18:1 ω7c. Based upon this polyphasic taxonomic study, strain NLS-7T represents a novel species of the genus Methylocystis, for which the name Methylocystis suflitae sp. nov. is proposed. The type strain is NLS-7T (=ATCC TSD-256T=DSM 112294T). The 16S rRNA gene and genome sequences of strain NLS-7T have been deposited in GenBank under accession numbers ON715489 and GCA_024448135.1, respectively.

The evolution and changing ecology of the African hominid oral microbiome.

The oral microbiome plays key roles in human biology, health, and disease, but little is known about the global diversity, variation, or evolution of this microbial community. To better understand the evolution and changing ecology of the human oral microbiome, we analyzed 124 dental biofilm metagenomes from humans, including Neanderthals and Late Pleistocene to present-day modern humans, chimpanzees, and gorillas, as well as New World howler monkeys for comparison. We find that a core microbiome of primarily biofilm structural taxa has been maintained throughout African hominid evolution, and these microbial groups are also shared with howler monkeys, suggesting that they have been important oral members since before the catarrhine-platyrrhine split ca. 40 Mya. However, community structure and individual microbial phylogenies do not closely reflect host relationships, and the dental biofilms of Homo and chimpanzees are distinguished by major taxonomic and functional differences. Reconstructing oral metagenomes from up to 100 thousand years ago, we show that the microbial profiles of both Neanderthals and modern humans are highly similar, sharing functional adaptations in nutrient metabolism. These include an apparent Homo-specific acquisition of salivary amylase-binding capability by oral streptococci, suggesting microbial coadaptation with host diet. We additionally find evidence of shared genetic diversity in the oral bacteria of Neanderthal and Upper Paleolithic modern humans that is not observed in later modern human populations. Differences in the oral microbiomes of African hominids provide insights into human evolution, the ancestral state of the human microbiome, and a temporal framework for understanding microbial health and disease.

Bacteroides vicugnae sp. nov. isolated from the fecal material of an alpaca.

Two strictly anaerobic, Gram-stain-negative rod-shaped bacterial isolates, A2-P53T and A1-P5, were isolated from an enrichment of fecal material from two alpacas (Vicugna pacos). Based on a comparative 16S rRNA gene sequence analysis, the isolates were assigned to the genus Bacteroides with the highest sequence similarities to Bacteroides koreensis YS-aM39T (A2- P53T 97.7 % and A1-P5 97.9 %). Additionally, the average nucleotide identity and digital DNA-DNA hybridization values between these isolates and their closest relatives within Bacteroides were less than 92.1 % and 49.1 %, respectively. The average nucleotide identity between isolates A2-P53T and A1-P5 was 99.9 %. The predominant cellular fatty acid for isolates A2-P53T and A1-P5 was C15:0 antesio. The G+C % content of the isolates was 41.7 %. Based on biochemical, phylogenetic, genotypic, and chemotaxonomic criteria, these isolates A2-P53T and A1-P5 represent two individual strains of a novel species within the genus Bacteroides for which the name Bacteroides vicugnae sp. nov. is proposed. The type strain of this species is strain A2-P53T (CCUG 77273T = CCM 9377T = NRRL B-65693T).

Reclassification of Clostridium cocleatum, Clostridium ramosum, Clostridium spiroforme and Clostridium saccharogumia as Thomasclavelia cocleata gen. nov., comb. nov., Thomasclavelia ramosa comb. nov., gen. nov., Thomasclavelia spiroformis comb. nov. and Thomasclavelia saccharogumia comb. nov.

The genus Clostridium is phenotypically and genotypically diverse, with many species phylogenetically located outside Clostridium sensu stricto. One such group consists of the species Clostridium cocleatum, Clostridium ramosum, Clostridium spiroforme and Clostridium saccharogumia (formally clostridial rRNA cluster XVIII) [1]. Sequencing of the 16S rRNA and, more recently, the results of genomic analyses have demonstrated that these species represent a coherent cluster separated from other closely related genera located in the family Coprobacillaceae within the order Erysipelotrichales [2]. In addition to phenotypic, phylogenetic and genomic comparisons, chemotaxonomic features were consistent between all four species, the predominant fatty acids were C16 : 0 and C18 : 1ω9c, while glucose and ribose were the whole cell sugars present in the cell walls. Furthermore, he results of peptidoglycan analysis indicated that meso-2,6-diaminopimelic acid was present as the diagnostic diamino acid in all four species. Biochemical profiles were also concordant with them being closely related species. Therefore, on the basis of phylogenetic, genomic, phenotypic and chemotaxonomic information, a novel genus, Thomasclavelia gen. nov., is proposed. It is suggested that Clostridium cocleatum, Clostridium ramosum, Clostridium spiroforme and Clostridium saccharogumia be transferred to this genus as Thomasclavelia cocleata comb. nov., Thomasclavelia ramosa comb. nov., Thomasclavelia saccharogumia comb. nov. and Thomasclavelia spiroformis comb. nov. The type species of the genus is Thomasclavelia ramosa CCUG 24038T (=ATCC 25582T=DSM 1402T).

Holtiella tumoricola gen. nov. sp. nov., isolated from a human clinical sample.

The diversity of bacteria associated with biopsy material obtained from patients with colorectal cancer was investigated using culture techniques. A novel bacterium, strain CC70AT, was isolated by diluting a sample of homogenized tissue in anaerobic medium, and then plating to yield a pure culture. Strain CC70AT was a Gram-positive, strictly anaerobic, motile, rod-shaped bacterium. Formate, but not acetate, was a fermentative end-product from growth in peptone-yeast extract and peptone-yeast-glucose broth. The G+C content of DNA from strain CC70AT was 34.9 mol%. 16S rRNA gene sequence analysis revealed that the isolate was part of the phylum Bacillota. The closest described relatives of strain CC70AT were Cellulosilyticum lentocellum (93.3 %) and Cellulosilyticum ruminicola (93.3 and 91.9% sequence similarity across 16S rRNA gene, respectively). According to the data obtained in this work, strain CC70AT represents a novel bacterium belonging to a new genus for which the name Holtiella tumoricola gen. nov., sp. nov. is proposed. The type strain for our described novel species is CC70AT (=DSM 27931T= JCM 30568T).

Reclassification of Facklamia ignava, Facklamia sourekii and Facklamia tabacinasalis as Falseniella ignava gen. nov., comb. nov., Hutsoniella sourekii gen. nov., comb. nov., and Ruoffia tabacinasalis gen. nov., comb. nov., and description of Ruoffia halotolerans sp. nov., isolated from hypersaline Inland Sea of Qatar.

A Gram-stain-positive, non-pigmented, coccus-shaped, facultatively anaerobic and α-hemolytic bacterium designated as INB8T was isolated from a hypersaline marine water sample collected at the Inland Sea of Qatar. The isolate was able to grow at 25-40 °C (optimum, 30 °C), at pH 5-11 and with 2-8% NaCl. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain INB8T was placed within the family Aerococcaceae with the highest sequence similarity to Facklamia tabacinasalis CCUG 30090T (99.5%), followed by Facklamia hominis CCUG 36813T (93.9%), Facklamia sourekii Y17312T (93.8%), Facklamia ignava CCUG 37419T (93.6%), Facklamia miroungae CCUG 42728T (93.5%), Suicoccus acidiformans ZY16052T (93.5%), Facklamia languida CCUG 37842T (93.2%), Ignavigranum ruoffiae (93.1%), and Dolosicoccus paucivorans DSM 15742T (90.8%). Average nucleotide identity and digital DNA-DNA hybridization values between strain INB8T and F. tabacinasalis CCUG 30090T were determined to be 94.5% and 58.9% respectively, confirming strain INB8T represents a novel species. The major fatty acids were C14:0, C16:0, C18:0 and C18:1 ω9c. The G + C content of strain INB8T determined from the genome was 36.3 mol%. Based on the phylogenetic, chemotaxonomic and phenotypic information, it is proposed that Facklamia tabacinasalis should be reclassified as Ruoffia tabacinasalis, Facklamia ignava be reclassified as Falseniella ignava, and Facklamia sourekii be reclassified Hutsoniella sourekii. It is further proposed that strain INB8T should be classified as a species of the genus Ruoffia for which the name Ruoffia halotolerans sp. nov. is proposed. The type strain is INB8T (= LMG 30291T = CCUG 70701T = QCC/B60/17T).

Ningiella ruwaisensis gen. nov., sp. nov., a member of the family Alteromonadaceae isolated from marine water of the Arabian Gulf.

Strain B66T was isolated from a marine water sample collected at Al Ruwais, located on the northern tip of Qatar. Cells were Gram-stain-negative, strictly aerobic and short- rod-shaped with a polar flagellum. The isolate was able to grow at 15-45 °C (optimum, 30 °C), at pH 5-11 (optimum, pH 6.5-8) and with 0-6 % NaCl. 16S rRNA gene sequence analysis revealed that strain B66T was affiliated with the family Alteromonadaceae, sharing the highest sequence similarities to the genera Alteromonas (93.7-95.4 %), Aestuariibacter (94.0-95.1 %), Agaribacter (93.3-93.7 %), Glaciecola (92.0-93.7 %), Marisendiminitalea (93.2-93.3 %) and Planctobacterium (92.9 %). In the phylogenetic trees, strain B66T demonstrated the novel organism formed a distinct lineage closely associated with Aestuariibacter and Planctobacterium. Major fatty acids were C16 : 0, summed feature 3 (C16 : 1 ω7c/C16 : 1 ω6c/iso-C15 : 0 2-OH and iso-C15 : 0 3-OH. The major respiratory quinone was ubiquinone-8 and the major polar lipids are phosphatidylglycerol and phosphatidylethanolamine. The DNA G+C content derived from the genome was 43.2 mol%. Based on the phenotypic, chemotaxonomic, phylogenetic and genomic data, strain B66T is considered to represent a novel species and genus for which the name Ningiella ruwaisensis gen. nov., sp. nov., is proposed. The type strain is B66T (=QCC B003/17T=LMG 30288 T=CCUG 70703T).

Comparison of extraction methods for recovering ancient microbial DNA from paleofeces.

OBJECTIVES: Paleofeces are valuable to archeologists and evolutionary biologists for their potential to yield health, dietary, and host information. As a rich source of preserved biomolecules from host-associated microorganisms, they can also provide insights into the recent evolution and changing ecology of the gut microbiome. However, there is currently no standard method for DNA extraction from paleofeces, which combine the dual challenges of complex biological composition and degraded DNA. Due to the scarcity and relatively poor preservation of paleofeces when compared with other archeological remains, it is important to use efficient methods that maximize ancient DNA (aDNA) recovery while also minimizing downstream taxonomic biases. METHODS: In this study, we use shotgun metagenomics to systematically compare the performance of five DNA extraction methods on a set of well-preserved human and dog paleofeces from Mexico (~1,300 BP). RESULTS: Our results show that all tested DNA extraction methods yield a consistent microbial taxonomic profile, but that methods optimized for ancient samples recover significantly more DNA. CONCLUSIONS: These results show promise for future studies that seek to explore the evolution of the human gut microbiome by comparing aDNA data with those generated in modern studies.

The efficacy of whole human genome capture on ancient dental calculus and dentin.

OBJECTIVES: Dental calculus is among the richest known sources of ancient DNA in the archaeological record. Although most DNA within calculus is microbial, it has been shown to contain sufficient human DNA for the targeted retrieval of whole mitochondrial genomes. Here, we explore whether calculus is also a viable substrate for whole human genome recovery using targeted enrichment techniques. MATERIALS AND METHODS: Total DNA extracted from 24 paired archaeological human dentin and calculus samples was subjected to whole human genome enrichment using in-solution hybridization capture and high-throughput sequencing. RESULTS: Total DNA from calculus exceeded that of dentin in all cases, and although the proportion of human DNA was generally lower in calculus, the absolute human DNA content of calculus and dentin was not significantly different. Whole genome enrichment resulted in up to four-fold enrichment of the human endogenous DNA content for both dentin and dental calculus libraries, albeit with some loss in complexity. Recovering more on-target reads for the same sequencing effort generally improved the quality of downstream analyses, such as sex and ancestry estimation. For nonhuman DNA, comparison of phylum-level microbial community structure revealed few differences between precapture and postcapture libraries, indicating that off-target sequences in human genome-enriched calculus libraries may still be useful for oral microbiome reconstruction. DISCUSSION: While ancient human dental calculus does contain endogenous human DNA sequences, their relative proportion is low when compared with other skeletal tissues. Whole genome enrichment can help increase the proportion of recovered human reads, but in this instance enrichment efficiency was relatively low when compared with other forms of capture. We conclude that further optimization is necessary before the method can be routinely applied to archaeological samples.

Oral microbiome diversity among Cheyenne and Arapaho individuals from Oklahoma.

OBJECTIVES: There is a major ascertainment bias in microbiome research, with individuals of predominately European ancestry living within metropolitan areas dominating most studies. Here we present a study of the salivary microbiome within a North American Indian community. This research is the culmination of four years of collaboration and community engagement with Cheyenne & Arapaho (C&A) tribal members from western Oklahoma. MATERIALS AND METHODS: Using 16S rRNA gene amplification and next-generation sequencing, we generated microbial taxonomic inventories for 37 individuals representing five towns within the C&A tribes. For comparison, we performed the same laboratory techniques on saliva samples from 20 non-native individuals (NNI) from Norman, Oklahoma. RESULTS: The C&A participants differ from the NNI in having reduced within-individual species richness and higher between-individual variation. Unsupervised clustering analyses reveal that three ecological groupings best fit the data, and while C&A individuals include assignments to all three groups, the NNI individuals are assigned to only one group. One of the ecological groups found exclusively among C&A participants was characterized by high abundance of the oral bacterial genus Prevotella. DISCUSSION: The C&A and NNI participants from Oklahoma have notable differences in their microbiome diversity, with a wider range of variation observed among the C&A individuals, including a higher frequency of bacteria implicated in systemic disorders. Overall, this study highlights the importance of engagement with indigenous communities, and the need for an improved understanding of human microbiome diversity among underrepresented groups and those individuals living outside of metropolitan areas.

Successful enrichment and recovery of whole mitochondrial genomes from ancient human dental calculus.

OBJECTIVES: Archaeological dental calculus is a rich source of host-associated biomolecules. Importantly, however, dental calculus is more accurately described as a calcified microbial biofilm than a host tissue. As such, concerns regarding destructive analysis of human remains may not apply as strongly to dental calculus, opening the possibility of obtaining human health and ancestry information from dental calculus in cases where destructive analysis of conventional skeletal remains is not permitted. Here we investigate the preservation of human mitochondrial DNA (mtDNA) in archaeological dental calculus and its potential for full mitochondrial genome (mitogenome) reconstruction in maternal lineage ancestry analysis. MATERIALS AND METHODS: Extracted DNA from six individuals at the 700-year-old Norris Farms #36 cemetery in Illinois was enriched for mtDNA using in-solution capture techniques, followed by Illumina high-throughput sequencing. RESULTS: Full mitogenomes (7-34×) were successfully reconstructed from dental calculus for all six individuals, including three individuals who had previously tested negative for DNA preservation in bone using conventional PCR techniques. Mitochondrial haplogroup assignments were consistent with previously published findings, and additional comparative analysis of paired dental calculus and dentine from two individuals yielded equivalent haplotype results. All dental calculus samples exhibited damage patterns consistent with ancient DNA, and mitochondrial sequences were estimated to be 92-100% endogenous. DNA polymerase choice was found to impact error rates in downstream sequence analysis, but these effects can be mitigated by greater sequencing depth. DISCUSSION: Dental calculus is a viable alternative source of human DNA that can be used to reconstruct full mitogenomes from archaeological remains. Am J Phys Anthropol 160:220-228, 2016. © 2016 The Authors American Journal of Physical Anthropology Published by Wiley Periodicals, Inc.

Evolutionary barriers to horizontal gene transfer in macrophage-associated Salmonella.

Horizontal gene transfer (HGT) is a powerful evolutionary force facilitating bacterial adaptation and emergence of novel phenotypes. Several factors, including environmental ones, are predicted to restrict HGT, but we lack systematic and experimental data supporting these predictions. Here, we address this gap by measuring the relative fitness of 44 genes horizontally transferred from Escherichia coli to Salmonella enterica in infection-relevant environments. We estimated the distribution of fitness effects in each environment and identified that dosage-dependent effects across different environments are a significant barrier to HGT. The majority of genes were found to be deleterious. We also found longer genes had stronger negative fitness consequences than shorter ones, showing that gene length was negatively associated with HGT. Furthermore, fitness effects of transferred genes were found to be environmentally dependent. In summary, a substantial fraction of transferred genes had a significant fitness cost on the recipient, with both gene characteristics and the environment acting as evolutionary barriers to HGT.

Oral metagenomes from Native American Ancestors reveal distinct microbial lineages in the pre-contact era.

OBJECTIVES: Limited studies have focused on how European contact and colonialism impacted Native American oral microbiomes, specifically, the diversity of commensal or opportunistically pathogenic oral microbes, which may be associated with oral diseases. Here, we studied the oral microbiomes of pre-contact Wichita Ancestors, in partnership with the Descendant community, The Wichita and Affiliated Tribes, Oklahoma, USA. MATERIALS AND METHODS: Skeletal remains of 28 Wichita Ancestors from 20 archeological sites (dating approximately to 1250-1450 CE) were paleopathologically assessed for presence of dental calculus and oral disease. DNA was extracted from calculus, and partial uracil deglycosylase-treated double-stranded DNA libraries were shotgun-sequenced using Illumina technology. DNA preservation was assessed, the microbial community was taxonomically profiled, and phylogenomic analyzes were conducted. RESULTS: Paleopathological analysis revealed signs of oral diseases such as caries and periodontitis. Calculus samples from 26 Ancestors yielded oral microbiomes with minimal extraneous contamination. Anaerolineaceae bacterium oral taxon 439 was found to be the most abundant bacterial species. Several Ancestors showed high abundance of bacteria typically associated with periodontitis such as Tannerella forsythia and Treponema denticola. Phylogenomic analyzes of Anaerolineaceae bacterium oral taxon 439 and T. forsythia revealed biogeographic structuring; strains present in the Wichita Ancestors clustered with strains from other pre-contact Native Americans and were distinct from European and/or post-contact American strains. DISCUSSION: We present the largest oral metagenome dataset from a pre-contact Native American population and demonstrate the presence of distinct lineages of oral microbes specific to the pre-contact Americas.

Localized cardiac small molecule trajectories and persistent chemical sequelae in experimental Chagas disease.

Post-infectious conditions present major health burdens but remain poorly understood. In Chagas disease (CD), caused by Trypanosoma cruzi parasites, antiparasitic agents that successfully clear T. cruzi do not always improve clinical outcomes. In this study, we reveal differential small molecule trajectories between cardiac regions during chronic T. cruzi infection, matching with characteristic CD apical aneurysm sites. Incomplete, region-specific, cardiac small molecule restoration is observed in animals treated with the antiparasitic benznidazole. In contrast, superior restoration of the cardiac small molecule profile is observed for a combination treatment of reduced-dose benznidazole plus an immunotherapy, even with less parasite burden reduction. Overall, these results reveal molecular mechanisms of CD treatment based on simultaneous effects on the pathogen and on host small molecule responses, and expand our understanding of clinical treatment failure in CD. This link between infection and subsequent persistent small molecule perturbation broadens our understanding of infectious disease sequelae.

Remembering St. Louis individual-structural violence and acute bacterial infections in a historical anatomical collection.

Incomplete documentary evidence, variable biomolecular preservation, and limited skeletal responses have hindered assessment of acute infections in the past. This study was initially developed to explore the diagnostic potential of dental calculus to identify infectious diseases, however, the breadth and depth of information gained from a particular individual, St. Louis Individual (St.LI), enabled an individualized assessment and demanded broader disciplinary introspection of ethical research conduct. Here, we document the embodiment of structural violence in a 23-year-old Black and/or African American male, who died of lobar pneumonia in 1930s St. Louis, Missouri. St.LI exhibits evidence of systemic poor health, including chronic oral infections and a probable tuberculosis infection. Metagenomic sequencing of dental calculus recovered three pre-antibiotic era pathogen genomes, which likely contributed to the lobar pneumonia cause of death (CoD): Klebsiella pneumoniae (13.8X); Acinetobacter nosocomialis (28.4X); and Acinetobacter junii (30.1X). Ante- and perimortem evidence of St.LI's lived experiences chronicle the poverty, systemic racism, and race-based structural violence experienced by marginalized communities in St. Louis, which contributed to St.LI's poor health, CoD, anatomization, and inclusion in the Robert J. Terry Anatomical Collection. These same embodied inequalities continue to manifest as health disparities affecting many contemporary communities in the United States.

Untargeted Fecal Metabolomic Analyses across an Industrialization Gradient Reveal Shared Metabolites and Impact of Industrialization on Fecal Microbiome-Metabolome Interactions.

The metabolome is a central determinant of human phenotypes and includes the plethora of small molecules produced by host and microbiome or taken up from exogenous sources. However, studies of the metabolome have so far focused predominantly on urban, industrialized populations. Through an untargeted metabolomic analysis of 90 fecal samples from human individuals from Africa and the Americas-the birthplace and the last continental expansion of our species, respectively-we characterized a shared human fecal metabolome. The majority of detected metabolite features were ubiquitous across populations, despite any geographic, dietary, or behavioral differences. Such shared metabolite features included hyocholic acid and cholesterol. However, any characterization of the shared human fecal metabolome is insufficient without exploring the influence of industrialization. Here, we show chemical differences along an industrialization gradient, where the degree of industrialization correlates with metabolomic changes. We identified differential metabolite features such as amino acid-conjugated bile acids and urobilin as major metabolic correlates of these behavioral shifts. Additionally, coanalyses with over 5,000 publicly available human fecal samples and cooccurrence probability analyses with the gut microbiome highlight connections between the human fecal metabolome and gut microbiome. Our results indicate that industrialization significantly influences the human fecal metabolome, but diverse human lifestyles and behavior still maintain a shared human fecal metabolome. This study represents the first characterization of the shared human fecal metabolome through untargeted analyses of populations along an industrialization gradient. IMPORTANCE As the world becomes increasingly industrialized, understanding the biological consequences of these lifestyle shifts and what it means for past, present, and future human health is critical. Indeed, industrialization is associated with rises in allergic and autoimmune health conditions and reduced microbial diversity. Exploring these health effects on a chemical level requires consideration of human lifestyle diversity, but understanding the significance of any differences also requires knowledge of what molecular components are shared between human groups. Our study reveals the key chemistry of the human gut as defined by varied industrialization-based differences and ubiquitous shared features. Ultimately, these novel findings extend our knowledge of human molecular biology, especially as it is influenced by lifestyle and behavior, and provide steps toward understanding how human biology has changed over our species' history.

Inherited and somatic mitochondrial DNA mutations in Guam amyotrophic lateral sclerosis and parkinsonism-dementia.

There is increasing evidence for mitochondrial dysfunction in neurodegenerative disorders, although the exact role of mitochondrial DNA (mtDNA) mutations in this process is unresolved. We investigated inherited and somatic mtDNA substitutions and deletions in Guam amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia (PD). Hypervariable segment 1 sequences of Chamorro mtDNA revealed that the odds ratio of a PD or ALS diagnosis was increased for individuals in the E1 haplogroup while individuals in the E2 haplogroup had decreased odds of an ALS or PD diagnosis. Once the disorders were examined separately, it became evident that PD was responsible for these results. When the entire mitochondrial genome was sequenced for a subset of individuals, the nonsynonymous mutation at nucleotide position 9080, shared by all E2 individuals, resulted in a significantly low odds ratio for a diagnosis of ALS or PD. Private polymorphisms found in transfer and ribosomal RNA regions were found only in ALS and PD patients in the E1 haplogroup. Somatic mtDNA deletions in the entire mtDNA genome were not associated with either ALS or PD. We conclude that mtDNA haplogroup effects may result in mitochondrial dysfunction in Guam PD and reflect Guam population history. Thus it is reasonable to consider Guam ALS and PD as complex disorders with both environmental prerequisites and small genetic effects.

Shifts in gut and vaginal microbiomes are associated with cancer recurrence time in women with ovarian cancer.

Many studies investigating the human microbiome-cancer interface have focused on the gut microbiome and gastrointestinal cancers. Outside of human papillomavirus driving cervical cancer, little is known about the relationship between the vaginal microbiome and other gynecological cancers, such as ovarian cancer. In this retrospective study, we investigated the relationship between ovarian cancer, platinum-free interval (PFI) length, and vaginal and gut microbiomes. We observed that Lactobacillus-dominated vaginal communities were less common in women with ovarian cancer, as compared to existing datasets of similarly aged women without cancer. Primary platinum-resistance (PPR) disease is strongly associated with survivability under one year, and we found over one-third of patients with PPR (PFI < 6 months, n = 17) to have a vaginal microbiome dominated by Escherichia (>20% relative abundance), while only one platinum super-sensitive (PFI > 24 months, n = 23) patient had an Escherichia-dominated microbiome. Additionally, L. iners was associated with little, or no, gross residual disease, while other Lactobacillus species were dominant in women with >1 cm gross residual disease. In the gut microbiome, we found patients with PPR disease to have lower phylogenetic diversity than platinum-sensitive patients. The trends we observe in women with ovarian cancer and PPR disease, such as the absence of Lactobacillus and presence of Escherichia in the vaginal microbiome as well as low gut microbiome phylogenetic diversity have all been linked to other diseases and/or pro-inflammatory states, including bacterial vaginosis and autoimmune disorders. Future prospective studies are necessary to explore the translational potential and underlying mechanisms driving these associations.

Analysis of global human gut metagenomes shows that metabolic resilience potential for short-chain fatty acid production is strongly influenced by lifestyle.

High taxonomic diversity in non-industrial human gut microbiomes is often interpreted as beneficial; however, it is unclear if taxonomic diversity engenders ecological resilience (i.e. community stability and metabolic continuity). We estimate resilience through genus and species-level richness, phylogenetic diversity, and evenness in short-chain fatty acid (SCFA) production among a global gut metagenome panel of 12 populations (n = 451) representing industrial and non-industrial lifestyles, including novel metagenomic data from Burkina Faso (n = 90). We observe significantly higher genus-level resilience in non-industrial populations, while SCFA production in industrial populations is driven by a few phylogenetically closely related species (belonging to Bacteroides and Clostridium), meaning industrial microbiomes have low resilience potential. Additionally, database bias obfuscates resilience estimates, as we were 2-5 times more likely to identify SCFA-encoding species in industrial microbiomes compared to non-industrial. Overall, we find high phylogenetic diversity, richness, and evenness of bacteria encoding SCFAs in non-industrial gut microbiomes, signaling high potential for resilience in SCFA production, despite database biases that limit metagenomic analysis of non-industrial populations.