Treatment of generalized infantile myofibromatosis with sorafenib and imatinib: A case report.

Infantile myofibromatosis (IM) is characterized by solitary musculoskeletal nodules presenting during infancy but can manifest as multiple lesions with visceral involvement. Multicentric IM with visceral involvement carries a high risk of mortality and there is no consensus on treatment. We present a case of a patient with multicentric IM and pulmonary involvement who progressed on several chemotherapeutic regimens and subsequently had a complete response to sorafenib and later imatinib. This report describes the novel use of sorafenib and imatinib to treat generalized IM and the role of continued tyrosine kinase inhibitor therapy to maintain remission.

Minimally Invasive Adenocarcinoma of the Lung as Second Malignant Neoplasm Following Pediatric Rhabdomyosarcoma.

Primary pulmonary tumors are extremely rare in the pediatric population; however, sporadic cases of invasive pulmonary adenocarcinoma as a second malignant neoplasm (SMN) have been described in survivors of pediatric cancers. Pediatric patients with rhabdomyosarcoma (RMS) have a particularly increased risk of developing a SMN when compared to the general population, though pulmonary adenocarcinoma has not been previously described in a RMS patient. A 12-year-old female previously treated for stage IV pelvic RMS was found to have a left pulmonary nodule on surveillance computed tomography. The nodule was detected 4.25 years after the completion of treatment, which included resection, chemotherapy, and radiation to the abdomen and pelvis. Wedge resection of the pulmonary lesion was performed with negative margins. Histopathological examination revealed minimally invasive adenocarcinoma. Pulmonary adenocarcinoma may rarely present as a SMN in pediatric cancer survivors. The pathogenesis of this association is not yet entirely clear, but may include chemotherapy-induced mutagenesis and/or genetic predisposition. As pulmonary adenocarcinoma may present as a lung lesion radiographically indistinguishable from metastatic RMS, it should be considered in the differential diagnosis of any pediatric RMS survivor presenting with a new pulmonary nodule, especially in cases with late recurrence.

Changes in attitudes, beliefs, and experiences related to pregnancy during graduate medical education training from 2005 to 2021.

Today, 50% of medical students are women, and residency and fellowship training years overlap with peak times for starting families. The authors describe attitudes toward pregnancy during residency and fellowship and report pregnancy rates and complications for female residents and resident partners across several decades. A web-based survey was emailed to 1,057 residents in 2005 (period 1) and 1,860 residents in 2021 (period 2). Anonymous surveys were sent to all trainees including pregnant trainees, affected co-trainees and trainee partners. Resident attitudes and pregnancy characteristics were compared between groups using the chi-square (χ2) test for categorical variables and the Kruskal-Wallis test for ordinal variables. A total of 442 residents (41.8%) responded to the 2005 survey, and 525 (28.2%) responded to the 2021 survey. Most residents who covered for a pregnant resident had positive feelings about covering for their colleagues during both time periods, although more positive attitudes were present during the period 2. Only about 10% of residents received compensation for their coverage during both time periods. Among residents with a pregnancy during training (i.e., themselves or partners), most characterized having a baby in training as "somewhat difficult" or "very difficult" at both time periods. Pregnancy complication rates were 33% and 44% for training years 2005 and 2021. As medical education evolves, training programs should be proactive in creating structured support systems for pregnant residents and resident partners to minimize adverse maternal and fetal outcomes and to improve training programs. Future studies are needed to elucidate the causality of higher-than-expected pregnancy complication rates.

Effect of an algae feed additive on reducing enteric methane emissions from cattle.

Alga 1.0, a product containing bromoform, was fed to cattle to evaluate its effects on methane (CH 4 ) and carbon dioxide (CO 2 ) emissions and diet digestibility. Twelve nonlactating, nonpregnant Jersey cows (490 ±â€…19 kg body weight) were used in four replicated 3 × 3 Latin squares with three periods, each consisting of 21 d. Cows were blocked by feed intake (averaged intakes over 4 wk prior to trial) and assigned randomly to one of three treatments. Treatments included Alga 1.0 fed at 0, 69, and 103 g/d in a 0.454 kg/d dry matter (DM) top-dress daily in a modified distillers grains plus solubles (MDGS) carrier. Diet consisted of 60% dry-rolled corn, 20% corn silage, 15% modified distillers grains, and 5% supplement (DM basis). Headbox-style indirect calorimeters were utilized to evaluate gas production from individual cows with two nonconsecutive 23-h collections in each period. Data were analyzed using the GLIMMIX procedure of SAS with cow within square as experimental unit and as a random effect, and treatment and period as fixed effects. Linear and quadratic contrasts were used to compare treatments. Feeding Alga 1.0 linearly reduced dry matter intake (DMI, P < 0.01) by 10.1% for 69 g/d inclusion and 13.3% for 103 g/d inclusion compared to the control. Nutrient intakes decreased linearly (P < 0.01) due to lower DMI, but nutrient digestibility was not impacted (P ≥ 0.28). Inclusion of Alga 1.0 did not impact gross energy or digestible energy concentration of the diets expressed as Mcal/kg DM (P ≥ 0.22) but did linearly reduce energy intake (Mcal/d; P < 0.01). Feeding Alga 1.0 linearly reduced enteric CH4 emissions measured as g/kg DMI (P < 0.01) by 39 and 64% for 69 g/d and 103 g/d inclusion, respectively. Linear reductions (P < 0.01) of 64% to 65% were also observed in enteric CH4 emissions when expressed per kilogram of DM or organic matter digested. Respired CO2 as g/d linearly decreased (P = 0.03) for cattle fed Alga 1.0 but did not differ when expressed as g/kg of DMI (P ≥ 0.23). Oxygen consumption did not differ between treatments for g/d and g/kg DMI (P ≥ 0.19). In conclusion, feeding Alga 1.0 reduced DMI up to 13.3%, did not impact digestibility, and significantly reduced CH4 emissions up to 63%.

Bacterial diversity and specific taxa are associated with decolonization of carbapenemase-producing enterobacterales after fecal microbiota transplantation.

OBJECTIVES: We evaluated the effect of fecal microbiota transplantation (FMT) on the clearance of carbapenemase-producing Enterobacterales (CPE) carriage. METHODS: We performed a prospective, multi-center study, conducted among patients who received a single dose of FMT from one of four healthy donors. The primary endpoint was complete clearance of CPE carriage two weeks after FMT with a secondary endpoint at three months. Shotgun metagenomic sequencing was performed to assess gut microbiota composition of donors and recipients before and after FMT. RESULTS: Twenty CPE-colonized patients were included in the study, where post-FMT 20% (n = 4/20) of patients met the primary endpoint and 40% (n = 8/20) of patients met the secondary endpoint. Kaplan-Meier curves between patients with FMT intervention and the control group (n = 82) revealed a similar rate of decolonization between groups. Microbiota composition analyses revealed that response to FMT was not donor-dependent. Responders had a significantly lower relative abundance of CPE species pre-FMT than non-responders, and 14 days post-FMT responders had significantly higher bacterial species richness and alpha diversity compared to non-responders (p < 0.05). Responder fecal samples were also enriched in specific species, with significantly higher relative abundances of Faecalibacterium prausnitzii, Parabacteroides distasonis, Collinsella aerofaciens, Alistipes finegoldii and Blautia_A sp900066335 (q<0.01) compared to non-responders. CONCLUSION: FMT administration using the proposed regimen did not achieve statistical significance for complete CPE decolonization but was correlated with the relative abundance of specific bacterial taxa, including CPE species.

Faecal Microbiota Transplantation Engraftment After Budesonide or Placebo in Patients With Active Ulcerative Colitis Using Pre-selected Donors: A Randomized Pilot Study.

BACKGROUND: Faecal microbiota transplantation [FMT] shows some efficacy in treating patients with ulcerative colitis [UC], although variability has been observed among donors and treatment regimens. We investigated the effect of FMT using rationally selected donors after pretreatment with budesonide or placebo in active UC. METHODS: Patients ≥18 years old with mild to moderate active UC were randomly assigned to 3 weeks of budesonide [9 mg] or placebo followed by 4-weekly infusions of a donor faeces suspension. Two donors were selected based on microbiota composition, regulatory T cell induction and short-chain fatty acid production in mice. The primary endpoint was engraftment of donor microbiota after FMT. In addition, clinical efficacy was assessed. RESULTS: In total, 24 patients were enrolled. Pretreatment with budesonide did not increase donor microbiota engraftment [p = 0.56] nor clinical response, and engraftment was not associated with clinical response. At week 14, 10/24 [42%] patients achieved [partial] remission. Remarkably, patients treated with FMT suspensions from one donor were associated with clinical response [80% of responders, p < 0.05] but had lower overall engraftment of donor microbiota. Furthermore, differences in the taxonomic composition of the donors and the engraftment of certain taxa were associated with clinical response. CONCLUSION: In this small study, pretreatment with budesonide did not significantly influence engraftment or clinical response after FMT. However, clinical response appeared to be donor-dependent. Response to FMT may be related to transfer of specific strains instead of overall engraftment, demonstrating the need to characterize mechanisms of actions of strains that maximize therapeutic benefit in UC.

Veterinary Dental Photobiomodulation: Assessing Post-Treatment Gingival Inflammation in Canines.

Objective: This research aims to determine the effect photobiomodulation treatment has on oral inflammation after routine dental prophylaxis in canines. Background: Photobiomodulation therapy after dental procedures has been documented to reduce inflammation in human and animal models. Methods: Canines were randomly assigned into three groups: control group (CG; n = 15), left side treated group (LTG; n = 15), and right side treated group (RTG; n = 15). The canines in the treatment groups received four points of irradiation [GaAlInP-650 nm, continuous wave (CW), 0.1 W, 0.2 W/cm2, 100 sec, 10 J, 20 J/cm2]. The gingiva was evaluated by a veterinary investigator blinded to the treatment groups for erythema and edema on the day following treatment. Student's t-test and Student's paired t-test were used for data analysis. Results: Reductions in composite inflammation (p = 0.008) and erythema (p = 0.030) were observed in the LTG relative to the CG at the location of the left dental arcade. Reductions in composite inflammation (p = 0.025) and erythema (p = 0.013) were also observed in the combined treated arcades of the LTG and RTG when compared to the CG. Conclusions: The results indicate that the canines who received a single photobiomodulation treatment on the left dental arcade demonstrated a decrease in inflammation and erythema.

Effect of increasing corn silage inclusion in finishing diets cattle with or without tylosin on performance and liver abscesses.

A pooled analysis was performed to evaluate whether corn silage fed at 15% or 45% of diet DM impacted liver abscesses prevalence at slaughter in five previous experiments. Cattle fed 15% corn silage had 7.8% abscessed livers compared to 4.1% for cattle fed 45% corn silage when all diets contained tylosin. While improved due to increased corn silage inclusion, the objective of the current finishing study was to determine the impact of silage inclusion in finishing diets with and without tylosin on performance and incidence of abscessed livers in beef cattle. A total of 640 (BW = 334 ± 25 kg) steers were used in a generalized randomized block design with a 2 × 2 factorial treatment design. Treatments included two concentrations of corn silage (15% and 45% of diet DM), with or without tylosin for liver abscesses. This study used 32 pens of cattle with 20 steers per pen and 8 pens per treatment. There was a tendency for an interaction for feed efficiency (G:F; P = 0.10) where cattle fed 15% corn silage had a 2% increase in G:F when tylosin was added to the diet, but no improvements in G:F were observed when tylosin was added to diets containing 45% silage. There was an interaction between silage and tylosin inclusion for abscessed livers (P = 0.05). Cattle fed 15% corn silage without tylosin had the greatest incidence of abscessed livers (34.5%) compared to other treatments (P = 0.05), and the incidence of abscessed livers was decreased to 19% if tylosin was fed with 15% corn silage. Feeding 45% silage was effective at lowering the incidence of abscessed livers (P = 0.05) which was 12.4%, regardless of whether tylosin was fed. Feeding corn silage at 45% of diet DM (77.5% concentrate) was as effective as feeding tylosin to cattle on a 92.5% concentrate diet. Feeding corn silage at greater inclusions decreased daily gain (P ≤ 0.01) but increased final body weight when fed to an equal fatness (cattle fed 45% CS were fed 28 d longer). Feeding corn silage at 45% was more economical compared to feeding 15% corn silage, especially as corn prices increase, provided shrink is well managed. Feeding elevated concentrations of corn silage may be an economically viable method to reduce incidence of liver abscesses without antibiotic use for smaller operations that can manage more corn silage in finishing diets.

Antibiotics are a very effective method to control liver abscesses for finishing cattle, which are thought to be due to high starch concentration and acidosis. Dietary roughage (forage) is used to control acidosis. As grain prices increase, feeding greater amounts of corn silage may be advantageous and silage can be an economical forage compared to other traditional forages like alfalfa. This study evaluated the impact of corn silage inclusion on performance and abscessed livers with and without the addition of antibiotics. As expected, feeding more corn silage decreased both gain and feed efficiency but also increased profitability. Feeding tylosin with a traditional inclusion of silage (15%) decreased abscessed livers from 34.5% to 19%. However, if cattle are fed more silage (45%) the incidence of abscessed livers was 12.4%, regardless of feeding tylosin or not.

Impact of shade in beef feedyards on performance, ear temperature, and heat stress measures.

A 2-yr study (year 1: March to September 2017; year 2: February to August 2018) was conducted using crossbred steers (year 1: n = 1677; initial body weight [BW] = 372 kg, SD = 47; year 2: n = 1713; initial BW = 379 kg, SD = 10) in a commercial feedyard study in Eastern NE to determine the effects of shade on cattle performance, ear temperature, and cattle activity. Two treatments were evaluated using a randomized complete block design (n = 5 blocks based on arrival). Treatments were assigned randomly to pens and consisted of five pens without shade (NO SHADE) and five pens with shade (SHADE). Ear temperatures were collected throughout the trials using biometric sensing ear tags on a subset of cattle. Panting scores were collected using a 5 point scale determined visually based on the level of panting occurring on the same subset of steers a minimum of twice weekly from June 8 to August 21 in year 1 and May 29 to July 24 in year 2 by one trained individual each year. In year 1, no differences (P ≥ 0.24) were observed for growth performance or carcass characteristics. Dry matter intake (DMI) and average daily gain (ADG) were greater (P ≤ 0.04) for SHADE cattle in year 2. Over the entire feeding period in year 1, greater (P < 0.01) ear temperature was observed for NO SHADE cattle, but cattle movement was not different (P = 0.38) between treatments. When evaluating the entire feeding period in year 2, cattle movement and ear temperature were not different (P ≥ 0.80) between treatments. Cattle in the SHADE treatment had lower (P ≤ 0.04) panting scores in years 1 and 2. These data suggest that providing shade can lessen the negative influence of heat events on DMI and was an effective way to reduce heat stress in feedlot operations, but only impacted ADG if heat events were close to the cattle slaughter date.

This study was performed over two separate summers to evaluate natural exposure to heat and quantify the impact that providing shade has on stress measures, estimates of body temperature, and feedlot performance. In the first year, cattle were marketed after summer heat events and while ear temperature and panting scores were decreased for cattle in shaded pens, the effect was not significant enough to influence performance parameters. In the second year when cattle were marketed more immediately following heat impacts, cattle fed in shaded pens consumed more feed and gained more weight than cattle fed in pens without shade. In both years, cattle decreased dry matter intakes to offset normal heat events.

Transient Suppression of Bacterial Populations Associated with Gut Health is Critical in Success of Exclusive Enteral Nutrition for Children with Crohn's Disease.

BACKGROUND AND AIMS: Exclusive enteral nutrition [EEN] is a dietary intervention to induce clinical remission in children with active luminal Crohn's disease [CD]. While changes in the gut microbial communities have been implicated in achieving this remission, a precise understanding of the role of microbial ecology in the restoration of gut homeostasis is lacking. METHODS: Here we reconstructed genomes from the gut metagenomes of 12 paediatric subjects who were sampled before, during and after EEN. We then classified each microbial population into distinct 'phenotypes' or patterns of response based on changes in their relative abundances throughout the therapy on a per-individual basis. RESULTS: Our data show that children achieving clinical remission during therapy were enriched with microbial populations that were either suppressed or that demonstrated a transient bloom as a function of EEN. In contrast, this ecosystem-level response was not observed in cases of EEN failure. Further analysis revealed that populations that were suppressed during EEN were significantly more prevalent in healthy children and adults across the globe compared with those that bloomed ephemerally during the therapy. CONCLUSIONS: These observations taken together suggest that successful outcomes of EEN are marked by a temporary emergence of microbial populations that are rare in healthy individuals, and a concomitant reduction in microbes that are commonly associated with gut homeostasis. Our work is a first attempt to highlight individual-specific, complex environmental factors that influence microbial response in EEN. This model offers a novel, alternative viewpoint to traditional taxonomic strategies used to characterize associations with health and disease states.

Microbes with higher metabolic independence are enriched in human gut microbiomes under stress.

A wide variety of human diseases are associated with loss of microbial diversity in the human gut, inspiring a great interest in the diagnostic or therapeutic potential of the microbiota. However, the ecological forces that drive diversity reduction in disease states remain unclear, rendering it difficult to ascertain the role of the microbiota in disease emergence or severity. One hypothesis to explain this phenomenon is that microbial diversity is diminished as disease states select for microbial populations that are more fit to survive environmental stress caused by inflammation or other host factors. Here, we tested this hypothesis on a large scale, by developing a software framework to quantify the enrichment of microbial metabolisms in complex metagenomes as a function of microbial diversity. We applied this framework to over 400 gut metagenomes from individuals who are healthy or diagnosed with inflammatory bowel disease (IBD). We found that high metabolic independence (HMI) is a distinguishing characteristic of microbial communities associated with individuals diagnosed with IBD. A classifier we trained using the normalized copy numbers of 33 HMI-associated metabolic modules not only distinguished states of health versus IBD, but also tracked the recovery of the gut microbiome following antibiotic treatment, suggesting that HMI is a hallmark of microbial communities in stressed gut environments.

Mineral composition of serially slaughtered Holstein steers supplemented with zilpaterol hydrochloride.

Calf-fed Holstein steers (n = 115; 449 ± 20 kg) were utilized in a serial harvest experiment. A baseline group of five steers was harvested after 226 d on feed (DOF), which was designated day 0. The remaining cattle were assigned randomly to 11 harvest groups, with slaughter every 28 d. Cattle were either not (CON) or were fed zilpaterol hydrochloride for 20 d followed by a 3 d withdrawal (ZH). There were five steers per treatment in each slaughter group ranging from days 28 to 308. Whole carcasses were divided into lean, bone, internal cavity, hide, and fat trim components. Apparent mineral retention (Ca, P, Mg, K, and S) within the body was calculated as the difference between mineral concentration at slaughter and day 0. Mineral concentration at day 0 was determined from body composition of steers harvested at day 0 multiplied by individual live body weight (BW) at day 0. All data were analyzed as a 2 × 11 factorial arrangement with individual animal as the experimental unit. Orthogonal contrasts were used to analyze linear and quadratic contrasts over time (11 slaughter dates). There were no differences in concentration of Ca, P, and Mg in bone tissue as feeding duration increased (P ≥ 0.89); concentration of K, Mg, and S in lean tissue did fluctuate across DOF (P < 0.01). Averaged across treatment and DOF, 99% of Ca, 92% of P, 78% of Mg, and 23% of S present in the body were in bone tissue; 67% of K and 49% of S were in lean tissue. Expressed as gram per day, apparent retention of all minerals decreased linearly across DOF (P < 0.01). Expressed relative to empty body weight (EBW) gain, apparent Ca, P, and K retention decreased linearly as BW increased (P < 0.01) whereas Mg and S increased linearly (P < 0.01). Apparent retention of Ca was greater for CON cattle (greater bone fraction) and apparent retention of K was greater for ZH cattle (greater muscle fraction) when expressed relative to EBW gain (P ≤ 0.02), demonstrating the increase in lean gain by ZH cattle. There were no differences in apparent retention of Ca, P, Mg, K, or S due to treatment (P ≥ 0.14) or time (P ≥ 0.11) when expressed relative to protein gain. Apparent retention averaged 14.4 g Ca, 7.5 g P, 0.45 g Mg, 1.3 g K, and 1.0 g S/100 g protein gain. Expressing apparent mineral retention on a protein gain basis minimized effects of rate and type of gain, allowing for better comparison across treatments and time. Feeding zilpaterol hydrochloride did not affect apparent mineral retention when expressed relative to protein gain.

Mineral requirements for feedlot cattle are largely based on measured mineral concentration in the body at harvest. Fairly extensive research has been done quantifying Ca and P in the body of cattle, but data on Mg, K, and S are sparse. Serial harvest experiments are expensive and labor intensive and therefore not conducted frequently. A group of 115 Holstein steers was fed a finishing diet with serial harvest every 28 d. Two treatments were evaluated, control and cattle fed zilpaterol hydrochloride to increase lean tissue growth. Every 28 d, five steers from each treatment group were harvested with the whole carcass divided into lean, bone, internal cavity, hide, and fat trim components. Apparent mineral retention was calculated as the difference between mineral composition at day 0 (baseline harvest group) and each 28 d harvest group. Averaged across treatment and days on feed, 99% of Ca, 92% of P, 78% of Mg, and 23% of S present in the body were measured in bone tissue; 67% of K and 49% of S were in lean tissue. Apparent retention averaged 14.4 g Ca, 7.5 g P, 0.45 g Mg, 1.3 g K, and 1.0 g S/100 g protein gain.

Metabolic independence drives gut microbial colonization and resilience in health and disease.

BACKGROUND: Changes in microbial community composition as a function of human health and disease states have sparked remarkable interest in the human gut microbiome. However, establishing reproducible insights into the determinants of microbial succession in disease has been a formidable challenge. RESULTS: Here we use fecal microbiota transplantation (FMT) as an in natura experimental model to investigate the association between metabolic independence and resilience in stressed gut environments. Our genome-resolved metagenomics survey suggests that FMT serves as an environmental filter that favors populations with higher metabolic independence, the genomes of which encode complete metabolic modules to synthesize critical metabolites, including amino acids, nucleotides, and vitamins. Interestingly, we observe higher completion of the same biosynthetic pathways in microbes enriched in IBD patients. CONCLUSIONS: These observations suggest a general mechanism that underlies changes in diversity in perturbed gut environments and reveal taxon-independent markers of "dysbiosis" that may explain why widespread yet typically low-abundance members of healthy gut microbiomes can dominate under inflammatory conditions without any causal association with disease.

Evaluation of the effects of wood-sourced biochar as a feedlot pen surface amendment on manure nutrient capture.

Feedstuffs utilized in U.S. feedlot finishing rations incorporate high concentrations of N and P, with less than 15% of fed N and P retained by the animal. The remaining N and P are excreted in the manure, where the opportunity for manure N loss via ammonia (NH3) volatilization from the feedlot pen surface is a risk to the environment and lowers the value of manure as a fertilizer. Two nutrient mass balance experiments were conducted during the winter and summer seasons to evaluate the effects of spreading unprocessed Eastern red cedar biochar onto the feedlot pen surface on manure nutrient capture and cattle performance. A 186-d feedlot finishing experiment was conducted from December to June (WINTER) and a subsequent 153-d finishing experiment was conducted from June to November (SUMMER). The WINTER experiment evaluated three treatments (5 pens per treatment; 10 steers per pen), including biochar spread on pen surface during the feeding period (1.40 kg biochar/m2; 17.6 m2/steer soil surface of the pen), hydrated lime spread on pen surface at end of feeding period (1.75 kg/m2) and control (no treatment applied). The SUMMER experiment evaluated biochar treatment (1.40 kg biochar/m2; 5 pens per treatment; 8 steers per pen; and 22 m2/steer soil surface of the pen) against control. There were no differences in N and P intake, retention, or excretion (P ≥ 0.38) between WINTER treatments. Steer performance (P ≥ 0.10) and carcass characteristics (P ≥ 0.50) were not impacted by pen treatment in WINTER. Nitrogen and P intake and excretion (P ≥ 0.35) were not different between treatments in SUMMER and retention of N and P was significantly greater for the biochar treatment (P ≤0.04) due to greater ADG (P = 0.05). There was no difference in DMI (P = 0.48) in SUMMER, steers on biochar pen treatment had heavier HCW (P = 0.05) and greater ADG, resulting in a tendency for greater feed efficiency (P = 0.08). In both experiments, biochar addition to the pen surface tended (P = 0.07) to increase manure N as a percent of manure DM, but this increase in N concentration did not impact kg of N removed from the feedlot pens (P ≥ 0.15) or N losses (P ≥ 0.68). The addition of red cedar biochar to the feedlot pen surface did not increase manure nutrient capture of N or P and did not reduce N losses associated with soil-based feedlot pens.

Functional Insights into the Kelp Microbiome from Metagenome-Assembled Genomes.

Eukaryotic organisms evolved in a microbial world and often have intimate associations with diverse bacterial groups. Kelp, brown macroalgae in the order Laminariales, play a vital role in coastal ecosystems, yet we know little about the functional role of the microbial symbionts that cover their photosynthetic surfaces. Here, we reconstructed 79 bacterial metagenome-assembled genomes (MAGs) from blades of the bull kelp, Nereocystis luetkeana, allowing us to determine their metabolic potential and functional roles. Despite the annual life history of bull kelp, nearly half of the bacterial MAGs were detected across multiple years. Diverse members of the kelp microbiome, spanning 6 bacterial phyla, contained genes for transporting and assimilating dissolved organic matter (DOM), which is secreted by kelp in large quantities and likely fuels the metabolism of these heterotrophic bacteria. Bacterial genomes also contained alginate lyase and biosynthesis genes, involved in polysaccharide degradation and biofilm formation, respectively. Kelp-associated bacterial genomes contained genes for dissimilatory nitrate reduction and urea hydrolysis, likely providing a reduced source of nitrogen to the host kelp. The genome of the most abundant member of the kelp microbiome and common macroalgal symbiont, Granulosicoccus, contained a full suite of genes for synthesizing cobalamin (vitamin B12), suggesting that kelp-associated bacteria have the potential to provide their host kelp with vitamins. Finally, kelp-associated Granulosicoccus contained genes that typify the aerobic anoxygenic phototrophic bacteria, including genes for bacteriochlorophyll synthesis and photosystem II reaction center proteins, making them the first known photoheterotrophic representatives of this genus. IMPORTANCE Kelp (brown algae in the order Laminariales) are foundational species that create essential habitat in temperate and arctic coastal marine ecosystems. These photosynthetic giants host millions of microbial taxa whose functions are relatively unknown, despite their potential importance for host-microbe interactions and nutrient cycling in kelp forest ecosystems. We reconstructed bacterial genomes from metagenomic samples collected from blades of the bull kelp, Nereocystis luetkeana, allowing us to determine the functional gene content of specific members of the kelp microbiome. These bacterial genomes spanned 6 phyla and 19 families and included common alga-associated microbial symbionts such as Granulosicoccus. Key functions encoded in kelp-associated bacterial genomes included dissolved organic matter assimilation, alginate metabolism, vitamin B12 biosynthesis, and nitrogen reduction from nitrate and urea to ammonium, potentially providing the host kelp with vitamins and reduced nitrogen.

The effect of corn silage hybrid and inclusion on performance of finishing steers and silage hybrid effects on digestibility and performance of growing steers.

Three experiments evaluated the effects of three corn silage hybrids, inclusion, and nutrient digestibility in growing and finishing diets. The three hybrids tested included a control (CON), a hybrid containing a brown midrib (bm3) trait (BM3), and an experimental bm3 hybrid with the soft endosperm trait (BM3-SOFT). Experiment 1 utilized 360 crossbred steers (body weight [BW] = 334; SD = 25 kg) to evaluate inclusion of silage in a finishing diet at (15% or 45% of diet dry matter [DM]) and silage hybrid (CON, BM3, or BM3-SOFT). Experiment 2 and 3 utilized 216 crossbred steers (BW = 324; SD = 10 kg) and six ruminally fistulated steers (BW = 274; SD = 27 kg), respectively, to evaluate effects of either CON, BM3, or BM3-SOFT silage hybrids on performance and nutrient digestibility in growing diets. In Exp. 1, there was a silage inclusion × hybrid interaction for average daily gain (ADG) and gain-to-feed ratio (G:F). All treatments with 15% silage had greater (P ≤ 0.04) ADG and G:F compared with 45% silage. Cattle fed BM3-SOFT had greater ADG and G:F than cattle fed CON or BM3 when silage was included at 15% of the diet. When silage was fed at 45% of the diet DM, ADG did not differ between cattle fed either bm3 hybrid. Cattle fed BM3 had the greatest G:F (P < 0.01), with no difference between BM3-SOFT and CON. At 15% silage inclusion, hot carcass weight (HCW) was greater (P < 0.01) for cattle fed BM3-SOFT compared with cattle fed CON and BM3 but did not differ between cattle fed BM3 and CON. At 45% silage inclusion, steers fed either bm3 hybrid did not differ in HCW but were both heavier (P < 0.01) compared with cattle fed CON. In Exp. 2, ending BW, dry matter intake (DMI), and ADG were greater (P < 0.01) for steers fed either bm3 hybrid compared to steers fed the CON, but not different between steers fed the bm3 hybrids. There were no differences (P = 0.26) in G:F between the silage hybrids. In Exp. 3, steers fed either bm3 had greater (P < 0.01) neutral detergent fiber (NDF) and acid detergent fiber (ADF) digestibility than steers fed the CON. Ruminal pH was lower (P < 0.01), and total volatile fatty acid (VFA) concentration was greater (P < 0.01) for steers fed bm3 hybrids compared to steers fed CON. Feeding silage with the bm3 trait improved fiber digestibility, which increased DMI and subsequent ADG in high-forage growing diets. Feeding corn silage with the bm3 trait improved performance compared to non-bm3 corn silage when included above typical roughage concentration.

Colonization of the live biotherapeutic product VE303 and modulation of the microbiota and metabolites in healthy volunteers.

Manipulation of the gut microbiota via fecal microbiota transplantation (FMT) has shown clinical promise in diseases such as recurrent Clostridioides difficile infection (rCDI). However, the variable nature of this approach makes it challenging to describe the relationship between fecal strain colonization, corresponding microbiota changes, and clinical efficacy. Live biotherapeutic products (LBPs) consisting of defined consortia of clonal bacterial isolates have been proposed as an alternative therapeutic class because of their promising preclinical results and safety profile. We describe VE303, an LBP comprising 8 commensal Clostridia strains under development for rCDI, and its early clinical development in healthy volunteers (HVs). In a phase 1a/b study in HVs, VE303 is determined to be safe and well-tolerated at all doses tested. VE303 strains optimally colonize HVs if dosed over multiple days after vancomycin pretreatment. VE303 promotes the establishment of a microbiota community known to provide colonization resistance.