Disentangling hindgut metabolism in the American cockroach through single-cell genomics and metatranscriptomics

Omnivorous cockroaches host a complex hindgut microbiota comprised of insect-specific lineages related to those found in mammalian omnivores. Many of these organisms have few cultured representatives, thereby limiting our ability to infer the functional capabilities of these microbes. Here we present a unique reference set of 96 high-quality single cell-amplified genomes (SAGs) from bacterial and archaeal cockroach gut symbionts. We additionally generated cockroach hindgut metagenomic and metatranscriptomic sequence libraries and mapped them to our SAGs. By combining these datasets, we are able to perform an in-depth phylogenetic and functional analysis to evaluate the abundance and activities of the taxa in vivo. Recovered lineages include key genera within Bacteroidota, including polysaccharide-degrading taxa from the genera Bacteroides, Dysgonomonas, and Parabacteroides, as well as a group of unclassified insect-associated Bacteroidales. We also recovered a phylogenetically diverse set of Firmicutes exhibiting a wide range of metabolic capabilities, including—but not limited to—polysaccharide and polypeptide degradation. Other functional groups exhibiting high relative activity in the metatranscriptomic dataset include multiple putative sulfate reducers belonging to families in the Desulfobacterota phylum and two groups of methanogenic archaea. Together, this work provides a valuable reference set with new insights into the functional specializations of insect gut symbionts and frames future studies of cockroach hindgut metabolism

Secondary somatic mutations restoring RAD51C and RAD51D associated with acquired resistance to the PARP inhibitor rucaparib in high-grade ovarian carcinoma

High-grade epithelial ovarian carcinomas (OC) containing mutated BRCA1 or BRCA2 (BRCA1/2) homologous recombination (HR) genes are sensitive to platinum-based chemotherapy and poly(ADP-ribose) polymerase inhibitors (PARPi), while restoration of HR function due to secondary mutations in BRCA1/2 has been recognized as an important resistance mechanism. We sequenced core HR pathway genes in 12 pairs of pre-treatment and post-progression tumor biopsy samples collected from patients in ARIEL2 Part 1, a phase 2 study of the PARPi rucaparib as treatment for platinum-sensitive, relapsed OC. In six of 12 pre-treatment biopsies, a truncation mutation in BRCA1, RAD51C or RAD51D was identified. In five of six paired post-progression biopsies, one or more secondary mutations restored the open reading frame. Four distinct secondary mutations and spatial heterogeneity were observed for RAD51C. In vitro complementation assays and a patient-derived xenograft (PDX), as well as predictive molecular modeling, confirmed that resistance to rucaparib was associated with secondary mutations

The hindgut microbiota of praying mantids is highly variable and includes both prey-associated and host-specific microbes.

Praying mantids are predators that consume a wide variety of insects. While the gut microbiome of carnivorous mammals is distinct from that of omnivores and herbivores, the role of the gut microbiome among predatory insects is relatively understudied. Praying mantids are the closest known relatives to termites and cockroaches, which are known for their diverse gut microbiota. However, little is known about the mantid gut microbiota or their importance to host health. In this work, we report the results of a 16S rRNA gene-based study of gut microbiome composition in adults and late-instar larvae of three mantid species. We found that the praying mantis gut microbiome exhibits substantial variation in bacterial diversity and community composition. The hindgut of praying mantids were often dominated by microbes that are present in low abundance or not found in the guts of their insect prey. Future studies will explore the role of these microbes in the digestion of the dietary substrates and/or the degradation of toxins produced by their insect prey

Development and Use of a Traditional Mexican Diet Score in Relation to Systemic Inflammation and Insulin Resistance among Women of Mexican Descent.

BackgroundWomen of Mexican descent are disproportionally affected by obesity, systemic inflammation, and insulin resistance (IR). Available approaches used to give scores to dietary patterns relative to dietary guidelines may not effectively capture traditional diets of Mexicans, who comprise the largest immigrant group in the United States.ObjectivesWe characterized an a priori traditional Mexican diet (MexD) score high in corn tortillas, beans, soups, Mexican mixed dishes (e.g., tamales), fruits, vegetables, full-fat milk, and Mexican cheeses and low in refined grains and added sugars and evaluated the association of the MexD score with systemic inflammation and IR in 493 postmenopausal participants in the Women's Health Initiative (WHI) who are of Mexican ethnic descent.MethodsThe MexD score was developed from the baseline (1993-1998) WHI food frequency questionnaire, which included Hispanic foods and was available in Spanish. Body mass index (BMI) was computed from baseline measured weight and height, and ethnicity was self-reported. Outcome variables were high sensitivity C-reactive protein (hsCRP), glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and triglyceride concentrations measured at follow-up (2012-2013). Multivariable linear and logistic regression models were used to test the associations of the MexD score with systemic inflammation and IR.ResultsThe mean ± SD MexD score was 5.8 ± 2.1 (12 maximum points) and was positively associated with intakes of carbohydrates, vegetable protein, and dietary fiber and inversely associated with intakes of added sugars and total fat (P < 0.01). Women with high compared with low MexD scores, consistent with a more-traditional Mexican diet, had 23% and 15% lower serum hsCRP (P < 0.05) and insulin concentrations, respectively (P < 0.05). Baseline BMI modified these associations such that lower MexD scores were associated with higher insulin and HOMA-IR in overweight/obese women (P-interaction <0.05).ConclusionThese findings suggest that greater adherence to a traditional Mexican diet could help reduce the future risk of systemic inflammation and IR in women of Mexican descent

Development and Use of a Traditional Mexican Diet Score in Relation to Systemic Inflammation and Insulin Resistance among Women of Mexican Descent

Background: Women of Mexican descent are disproportionally affected by obesity, systemic inflammation, and insulin resistance (IR). Available approaches used to give scores to dietary patterns relative to dietary guidelines may not effectively capture traditional diets of Mexicans, who comprise the largest immigrant group in the United States. Objectives: We characterized an a priori traditional Mexican diet (MexD) score high in corn tortillas, beans, soups, Mexican mixed dishes (e.g., tamales), fruits, vegetables, full-fat milk, and Mexican cheeses and low in refined grains and added sugars and evaluated the association of the MexD score with systemic inflammation and IR in 493 postmenopausal participants in the Women’s Health Initiative (WHI) who are of Mexican ethnic descent. Methods: The MexD score was developed from the baseline (1993–1998) WHI food frequency questionnaire, which included Hispanic foods and was available in Spanish. Body mass index (BMI) was computed from baseline measured weight and height, and ethnicity was self-reported. Outcome variables were high sensitivity C-reactive protein (hsCRP), glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and triglyceride concentrations measured at follow-up (2012–2013). Multivariable linear and logistic regression models were used to test the associations of the MexD score with systemic inflammation and IR. Results: The mean ± SD MexD score was 5.8 ± 2.1 (12 maximum points) and was positively associated with intakes of carbohydrates, vegetable protein, and dietary fiber and inversely associated with intakes of added sugars and total fat (P < 0.01). Women with high compared with low MexD scores, consistent with a more-traditional Mexican diet, had 23% and 15% lower serum hsCRP (P < 0.05) and insulin concentrations, respectively (P < 0.05). Baseline BMI modified these associations such that lower MexD scores were associated with higher insulin and HOMA-IR in overweight/obese women (P-interaction <0.05). Conclusion: These findings suggest that greater adherence to a traditional Mexican diet could help reduce the future risk of systemic inflammation and IR in women of Mexican descent