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1. The faecal metabolome of black howler monkeys ( Alouatta pigra ) varies in response to seasonal dietary changes

   https://doi.org/10.1111/mec.16559  

   Mallott, Elizabeth K. ; Skovmand, Lotte H. ; Garber, Paul A. ; Amato, Katherine R. ( June 2022 , Molecular Ecology)

   Mammals rely on the metabolic functions of their gut microbiota to meet their energetic needs and digest potentially toxic components in their diet. The gut microbiome plastically responds to shifts in host diet and may buffer variation in energy and nutrient availability. However, it is unclear how seasonal differences in the gut microbiome influence microbial metabolism and nutrients available to hosts. In this study, we examine seasonal variation in the gut metabolome of black howler monkeys (Alouatta pigra) to determine whether those variations are associated with differences in gut microbiome composition and nutrient intake, and if plasticity in the gut microbiome buffers shortfalls in energy or nutrient intake. We integrated data on the metabolome of 81 faecal samples from 16 individuals collected across three distinct seasons with gut microbiome, nutrient intake and plant metabolite consumption data from the same period. Faecal metabolite profiles differed significantly between seasons and were strongly associated with changes in plant metabolite consumption. However, microbial community composition and faecal metabolite composition were not strongly associated. Additionally, the connectivity and stability of faecal metabolome networks varied seasonally, with network connectivity being highest during the dry, fruit‐dominated season when black howler monkey diets were calorically and nutritionally constrained. Network stability was highest during the dry, leaf‐dominated season when most nutrients were being consumed at intermediate rates. Our results suggest that the gut microbiome buffers seasonal variation in dietary intake, and that the buffering effect is most limited when host diet becomes calorically or nutritionally restricted.

    

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2. The effects of bone morphogenetic protein 2 and thrombopoietin treatment on angiogenic properties of endothelial cells derived from the lung and bone marrow of young and aged, male and female mice

   https://doi.org/10.1096/fj.202001616RR  

   Dadwal, Ushashi C. ; Bhatti, Fazal Ur Rehman ; Awosanya, Olatundun D. ; Nagaraj, Rohit U. ; Perugini, III, Anthony J. ; Sun, Seungyup ; Valuch, Conner R. ; de Andrade Staut, Caio ; Mendenhall, Stephen K. ; Tewari, Nikhil P. ; et al ( August 2021 , The FASEB Journal)

   With an aging world population, there is an increased risk of fracture and impaired healing. One contributing factor may be aging‐associated decreases in vascular function; thus, enhancing angiogenesis could improve fracture healing. Both bone morphogenetic protein 2 (BMP‐2) and thrombopoietin (TPO) have pro‐angiogenic effects. The aim of this study was to investigate the effects of treatment with BMP‐2 or TPO on the in vitro angiogenic and proliferative potential of endothelial cells (ECs) isolated from lungs (LECs) or bone marrow (BMECs) of young (3‐4 months) and old (22‐24 months), male and female, C57BL/6J mice. Cell proliferation, vessel‐like structure formation, migration, and gene expression were used to evaluate angiogenic properties. In vitro characterization of ECs generally showed impaired vessel‐like structure formation and proliferation in old ECs compared to young ECs, but improved migration characteristics in old BMECs. Differential sex‐based angiogenic responses were observed, especially with respect to drug treatments and gene expression. Importantly, these studies suggest that NTN1, ROBO2, and SLIT3, along with angiogenic markers (CD31, FLT‐1, ANGPT1, and ANGP2) differentially regulate EC proliferation and functional outcomes based on treatment, sex, and age. Furthermore, treatment of old ECs with TPO typically improved vessel‐like structure parameters, but impaired migration. Thus, TPO may serve as an alternative treatment to BMP‐2 for fracture healing in aging owing to improved angiogenesis and fracture healing, and the lack of side effects associated with BMP‐2.

    

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3. The gut microbiome influences host diet selection behavior

   https://doi.org/10.1073/pnas.2117537119  

   Trevelline, Brian K. ; Kohl, Kevin D. ( April 2022 , Proceedings of the National Academy of Sciences)

   Diet selection is a fundamental aspect of animal behavior with numerous ecological and evolutionary implications. While the underlying mechanisms are complex, the availability of essential dietary nutrients can strongly influence diet selection behavior. The gut microbiome has been shown to metabolize many of these same nutrients, leading to the untested hypothesis that intestinal microbiota may influence diet selection. Here, we show that germ-free mice colonized by gut microbiota from three rodent species with distinct foraging strategies differentially selected diets that varied in macronutrient composition. Specifically, we found that herbivore-conventionalized mice voluntarily selected a higher protein:carbohydrate (P:C) ratio diet, while omnivore- and carnivore-conventionalized mice selected a lower P:C ratio diet. In support of the long-standing hypothesis that tryptophan—the essential amino acid precursor of serotonin—serves as a peripheral signal regulating diet selection, bacterial genes involved in tryptophan metabolism and plasma tryptophan availability prior to the selection trial were significantly correlated with subsequent voluntary carbohydrate intake. Finally, herbivore-conventionalized mice exhibited larger intestinal compartments associated with microbial fermentation, broadly reflecting the intestinal morphology of their donor species. Together, these results demonstrate that gut microbiome can influence host diet selection behavior, perhaps by mediating the availability of essential amino acids, thereby revealing a mechanism by which the gut microbiota can influence host foraging behavior. 

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4. Profiling the human intestinal environment under physiological conditions

   https://doi.org/10.1038/s41586-023-05989-7  

   Shalon, Dari ; Culver, Rebecca Neal ; Grembi, Jessica A. ; Folz, Jacob ; Treit, Peter V. ; Shi, Handuo ; Rosenberger, Florian A. ; Dethlefsen, Les ; Meng, Xiandong ; Yaffe, Eitan ; et al ( May 2023 , Nature)

   The spatiotemporal structure of the human microbiome^1,2, proteome³and metabolome^4,5reflects and determines regional intestinal physiology and may have implications for disease⁶. Yet, little is known about the distribution of microorganisms, their environment and their biochemical activity in the gut because of reliance on stool samples and limited access to only some regions of the gut using endoscopy in fasting or sedated individuals⁷. To address these deficiencies, we developed an ingestible device that collects samples from multiple regions of the human intestinal tract during normal digestion. Collection of 240 intestinal samples from 15 healthy individuals using the device and subsequent multi-omics analyses identified significant differences between bacteria, phages, host proteins and metabolites in the intestines versus stool. Certain microbial taxa were differentially enriched and prophage induction was more prevalent in the intestines than in stool. The host proteome and bile acid profiles varied along the intestines and were highly distinct from those of stool. Correlations between gradients in bile acid concentrations and microbial abundance predicted species that altered the bile acid pool through deconjugation. Furthermore, microbially conjugated bile acid concentrations exhibited amino acid-dependent trends that were not apparent in stool. Overall, non-invasive, longitudinal profiling of microorganisms, proteins and bile acids along the intestinal tract under physiological conditions can help elucidate the roles of the gut microbiome and metabolome in human physiology and disease.

    

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5. Developmental exposure of California mice to endocrine disrupting chemicals and potential effects on the microbiome-gut-brain axis at adulthood

   https://doi.org/10.1038/s41598-020-67709-9  

   Kaur, Sarabjit ; Sarma, Saurav J. ; Marshall, Brittney L. ; Liu, Yang ; Kinkade, Jessica A. ; Bellamy, Madison M. ; Mao, Jiude ; Helferich, William G. ; Schenk, A. Katrin ; Bivens, Nathan J. ; et al ( July 2020 , Scientific Reports)

   Xenoestrogens are chemicals found in plant products, such as genistein (GEN), and in industrial chemicals, e.g., bisphenol A (BPA), present in plastics and other products that are prevalent in the environment. Early exposure to such endocrine disrupting chemicals (EDC) may affect brain development by directly disrupting neural programming and/or through the microbiome-gut-brain axis. To test this hypothesis, California mice (Peromyscus californicus) offspring were exposed through the maternal diet to GEN (250 mg/kg feed weight) or BPA (5 mg/kg feed weight, low dose- LD or 50 mg/kg, upper dose-UD), and dams were placed on these diets two weeks prior to breeding, throughout gestation, and lactation. Various behaviors, gut microbiota, and fecal metabolome were assessed at 90 days of age. The LD but not UD of BPA exposure resulted in individuals spending more time engaging in repetitive behaviors. GEN exposed individuals were more likely to exhibit such behaviors and showed socio-communicative disturbances. BPA and GEN exposed females had increased number of metabolites involved in carbohydrate metabolism and synthesis. Males exposed to BPA or GEN showed alterations in lysine degradation and phenylalanine and tyrosine metabolism. Current findings indicate cause for concern that developmental exposure to BPA or GEN might affect the microbiome-gut-brain axis.

    

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