Dietary-Induced Bacterial Metabolites Reduce Inflammation and Inflammation-Associated Cancer via Vitamin D Pathway.

Environmental factors, including westernised diets and alterations to the gut microbiota, are considered risk factors for inflammatory bowel diseases (IBD). The mechanisms underpinning diet-microbiota-host interactions are poorly understood in IBD. We present evidence that feeding a lard-based high-fat (HF) diet can protect mice from developing DSS-induced acute and chronic colitis and colitis-associated cancer (CAC) by significantly reducing tumour burden/incidence, immune cell infiltration, cytokine profile, and cell proliferation. We show that HF protection was associated with increased gut microbial diversity and a significant reduction in Proteobacteria and an increase in Firmicutes and Clostridium cluster XIVa abundance. Microbial functionality was modulated in terms of signalling fatty acids and bile acids (BA). Faecal secondary BAs were significantly induced to include moieties that can activate the vitamin D receptor (VDR), a nuclear receptor richly represented in the intestine and colon. Indeed, colonic VDR downstream target genes were upregulated in HF-fed mice and in combinatorial lipid-BAs-treated intestinal HT29 epithelial cells. Collectively, our data indicate that HF diet protects against colitis and CAC risk through gut microbiota and BA metabolites modulating vitamin D targeting pathways. Our data highlights the complex relationship between dietary fat-induced alterations of microbiota-host interactions in IBD/CAC pathophysiology.

Prone positioning for mechanically ventilated patients with coronavirus disease 2019: the experience of an Irish regional hospital intensive care unit.

BACKGROUND: The benefits of prone positioning in acute respiratory distress syndrome (ARDS) have been known for many years. While some controversy exists regarding whether coronavirus disease 2019 (COVID-19) pneumonia should be treated with the same therapeutic strategies as for non-COVID ARDS, the Surviving Sepsis Campaign still provide a weak recommendation to utilise prone positioning in this setting. AIMS: The aims of this study are to ascertain if prone positioning improves oxygenation significantly in mechanically ventilated patients with severe COVID-19 ARDS and to describe the feasibility of frequent prone positioning in an Irish regional hospital intensive care unit (ICU) with limited prior experience. METHODS: In this retrospective, observational cohort study, we investigate if the PaO2/FiO2 ratio and ventilatory ratio improve during and following prone positioning, and whether this improvement correlates with patient baseline characteristics or survival. RESULTS: Between March 2020 and 2021, 12 patients underwent prone positioning while mechanically ventilated for severe COVID ARDS. Sixty-six percent were male, mean age 60.9 (± 10.5), mean BMI 33.5 (± 6.74) and median APACHE II score on admission to ICU was 10.5 (7.25-16.3). Further, 83% were proned within 24 h of being intubated due to refractory hypoxaemia. PaO2/FiO2 ratio improved from 11.6 kPa (9.80-13.8) to 15.80 kPa (13.1-19.6) while prone, p < 0.0001. CONCLUSIONS: We found prone positioning to be a safe method of significantly improving oxygenation in mechanically ventilated patients with severe COVID-19 ARDS. We did not find a relationship between patient baseline characteristics nor illness severity and degree of PaO2/FiO2 ratio improvement, nor did we find a relationship between degree of PaO2/FiO2 ratio improvement and survival.

Microbotanical residues for the study of early hominin tools.

More than 2 million years ago in East Africa, the earliest hominin stone tools evolved amidst changes in resource base, with pounding technology playing a key role in this adaptive process. Olduvai Gorge (now Oldupai) is a famed locality that remains paramount for the study of human evolution, also yielding some of the oldest battering tools in the world. However, direct evidence of the resources processed with these technologies is lacking entirely. One way to obtain this evidence is through the analysis of surviving residues. Yet, linking residues with past processing activities is not simple. In the case of plant exploitation, this link can only be established by assessing site-based reference collections inclusive of both anthropogenic and natural residues as a necessary first step and comparative starting point. In this paper, we assess microbotanical remains from rock clasts sourced at the same quarry utilized by Oldowan hominins at Oldupai Gorge. We mapped this signal and analysed it quantitatively to classify its spatial distribution objectively, extracting proxies for taxonomic identification and further comparison with freestanding soils. In addition, we used blanks to manufacture pounding tools for blind, controlled replication of plant processing. We discovered that stone blanks are in fact environmental reservoirs in which plant remains are trapped by lithobionts, preserved as hardened accretions. Tool use, on the other hand, creates residue clusters; however, their spatial distribution can be discriminated from purely natural assemblages by the georeferencing of residues and statistical analysis of resulting patterns. To conclude, we provide a protocol for best practice and a workflow that has the advantage of overcoming environmental noise, reducing the risk of false positive, delivering a firm understanding of residues as polygenic mixtures, a reliable use of controls, and most importantly, a stronger link between microbotanical remains and stone tool use.

Earliest Olduvai hominins exploited unstable environments ~ 2 million years ago.

Rapid environmental change is a catalyst for human evolution, driving dietary innovations, habitat diversification, and dispersal. However, there is a dearth of information to assess hominin adaptions to changing physiography during key evolutionary stages such as the early Pleistocene. Here we report a multiproxy dataset from Ewass Oldupa, in the Western Plio-Pleistocene rift basin of Olduvai Gorge (now Oldupai), Tanzania, to address this lacuna and offer an ecological perspective on human adaptability two million years ago. Oldupai's earliest hominins sequentially inhabited the floodplains of sinuous channels, then river-influenced contexts, which now comprises the oldest palaeolake setting documented regionally. Early Oldowan tools reveal a homogenous technology to utilise diverse, rapidly changing environments that ranged from fern meadows to woodland mosaics, naturally burned landscapes, to lakeside woodland/palm groves as well as hyper-xeric steppes. Hominins periodically used emerging landscapes and disturbance biomes multiple times over 235,000 years, thus predating by more than 180,000 years the earliest known hominins and Oldowan industries from the Eastern side of the basin.

Isotopic and microbotanical insights into Iron Age agricultural reliance in the Central African rainforest.

The emergence of agriculture in Central Africa has previously been associated with the migration of Bantu-speaking populations during an anthropogenic or climate-driven 'opening' of the rainforest. However, such models are based on assumptions of environmental requirements of key crops (e.g. Pennisetum glaucum) and direct insights into human dietary reliance remain absent. Here, we utilise stable isotope analysis (δ13C, δ15N, δ18O) of human and animal remains and charred food remains, as well as plant microparticles from dental calculus, to assess the importance of incoming crops in the Congo Basin. Our data, spanning the early Iron Age to recent history, reveals variation in the adoption of cereals, with a persistent focus on forest and freshwater resources in some areas. These data provide new dietary evidence and document the longevity of mosaic subsistence strategies in the region.

Soil and plant phytoliths from the Acacia-Commiphora mosaics at Oldupai Gorge (Tanzania).

This article studies soil and plant phytoliths from the Eastern Serengeti Plains, specifically the Acacia-Commiphora mosaics from Oldupai Gorge, Tanzania, as present-day analogue for the environment that was contemporaneous with the emergence of the genus Homo. We investigate whether phytolith assemblages from recent soil surfaces reflect plant community structure and composition with fidelity. The materials included 35 topsoil samples and 29 plant species (20 genera, 15 families). Phytoliths were extracted from both soil and botanical samples. Quantification aimed at discovering relationships amongst the soil and plant phytoliths relative distributions through Chi-square independence tests, establishing the statistical significance of the relationship between categorical variables within the two populations. Soil assemblages form a spectrum, or cohort of co-ocurring phytolith classes, that will allow identifying environments similar to those in the Acacia-Commiphora ecozone in the fossil record.

A Machine Learning Approach to Bridge-Damage Detection Using Responses Measured on a Passing Vehicle.

This paper proposes a new two-stage machine learning approach for bridge damage detection using the responses measured on a passing vehicle. In the first stage, an artificial neural network (ANN) is trained using the vehicle responses measured from multiple passes (training data set) over a healthy bridge. The vehicle acceleration or Discrete Fourier Transform (DFT) spectrum of the acceleration is used. The vehicle response is predicted from its speed for multiple passes (monitoring data set) over the bridge. Root-mean-square error is used to calculate the prediction error, which indicates the differences between the predicted and measured responses for each passage. In the second stage of the proposed method, a damage indicator is defined using a Gaussian process that detects the changes in the distribution of the prediction errors. It is suggested that if the bridge condition is healthy, the distribution of the prediction errors will remain low. A recognizable change in the distribution might indicate a damage in the bridge. The performance of the proposed approach was evaluated using numerical case studies of vehicle-bridge interaction. It was demonstrated that the approach could successfully detect the damage in the presence of road roughness profile and measurement noise, even for low damage levels.

Genus-Wide Assessment of Antibiotic Resistance in Lactobacillus spp.

Lactobacillus species are widely used as probiotics and starter cultures for a variety of foods, supported by a long history of safe usage. Although more than 35 species meet the European Food Safety Authority (EFSA) criteria for qualified presumption of safety status, the safety of Lactobacillus species and their carriage of antibiotic resistance (AR) genes is under continuing ad hoc review. To comprehensively update the identification of AR in the genus Lactobacillus, we determined the antibiotic susceptibility patterns of 182 Lactobacillus type strains and compared these phenotypes to their genotypes based on genome-wide annotations of AR genes. Resistances to trimethoprim, vancomycin, and kanamycin were the most common phenotypes. A combination of homology-based screening and manual annotation identified genes encoding resistance to aminoglycosides (20 sequences), tetracycline (18), erythromycin (6), clindamycin (60), and chloramphenicol (42). In particular, the genes aac(3) and lsa, involved in resistance to aminoglycosides and clindamycin, respectively, were found in Lactobacillus spp. Acquired determinants predicted to code for tetracycline and erythromycin resistance were detected in Lactobacillus ingluviei, Lactobacillus amylophilus, and Lactobacillus amylotrophicus, flanked in the genome by mobile genetic elements with potential for horizontal transfer.IMPORTANCELactobacillus species are generally considered to be nonpathogenic and are used in a wide variety of foods and products for humans and animals. However, many of the species examined in this study have antibiotic resistance levels which exceed those recommended by the EFSA, suggesting that these cutoff values should be reexamined in light of the genetic basis for resistance discussed here. Our data provide evidence for rationally revising the regulatory guidelines for safety assessment of lactobacilli entering the food chain as starter cultures, food preservatives, or probiotics and will facilitate comprehensive genotype-based assessment of strains for safety screening.

The Root-Ely Modified Test of Rectus Femoris Spasticity Has Reliability in Individuals with Cerebral Palsy.

BACKGROUND: Stiff-knee gait is a common gait deviation in individuals with cerebral palsy (CP) due to rectus femoris (RF) muscle spasticity. The Duncan-Ely test is a velocity-dependent measurement of spasticity that is recorded as positive or negative. At our institution, we use a modification of the Duncan-Ely test, a 5-point ordinal rating scale, which delineates where the catch occurs within the rapid arc of knee flexion. It has been named the Root-Ely test. QUESTIONS/PURPOSES: We sought to determine the intra- and inter-rater reliability of the Duncan-Ely and Root-Ely tests in pediatric patients with CP. METHODS: A convenience sample of 20 ambulatory subjects was recruited; mean age was 10.5 ± 4.5 years, and the Gross Motor Function Classification System (GMFCS) levels were I-III. Five clinicians measured each individual's RF spasticity using the Root-Ely protocol during a single visit. Simple κ statistics with 95% confidence intervals (CI) were utilized for intra-rater reliability and weighted κ statistics with 95% CI for inter-rater reliability. RESULTS: The Root-Ely scale intra-rater reliability was 0.77 to 0.90 and inter-rater reliability was 0.32 to 0.87. Inter-rater reliability was good to excellent among experienced clinicians and fair to moderate in new clinicians. CONCLUSION: The Root-Ely 5-point scale has acceptable intra- and inter-rater reliability in pediatric individuals with CP among experienced clinicians. The Root-Ely test allows experienced clinicians to reliably quantify severity of RF spasticity and may give orthopaedic surgeons a clinical tool to better predict ideal candidates for RF transfers in individuals with CP in order to improve stiff-knee gait.

Exercise and the microbiota.

Sedentary lifestyle is linked with poor health, most commonly obesity and associated disorders, the corollary being that exercise offers a preventive strategy. However, the scope of exercise biology extends well beyond energy expenditure and has emerged as a great 'polypill', which is safe, reliable and cost-effective not only in disease prevention but also treatment. Biological mechanisms by which exercise influences homeostasis are becoming clearer and involve multi-organ systemic adaptations. Most of the elements of a modern lifestyle influence the indigenous microbiota but few studies have explored the effect of increased physical activity. While dietary responses to exercise obscure the influence of exercise alone on gut microbiota, professional athletes operating at the extremes of performance provide informative data. We assessed the relationship between extreme levels of exercise, associated dietary habits and gut microbiota composition, and discuss potential mechanisms by which exercise may exert a direct or indirect influence on gut microbiota.

Exercise and associated dietary extremes impact on gut microbial diversity.

OBJECTIVE: The commensal microbiota, host immunity and metabolism participate in a signalling network, with diet influencing each component of this triad. In addition to diet, many elements of a modern lifestyle influence the gut microbiota but the degree to which exercise affects this population is unclear. Therefore, we explored exercise and diet for their impact on the gut microbiota. DESIGN: Since extremes of exercise often accompany extremes of diet, we addressed the issue by studying professional athletes from an international rugby union squad. Two groups were included to control for physical size, age and gender. Compositional analysis of the microbiota was explored by 16S rRNA amplicon sequencing. Each participant completed a detailed food frequency questionnaire. RESULTS: As expected, athletes and controls differed significantly with respect to plasma creatine kinase (a marker of extreme exercise), and inflammatory and metabolic markers. More importantly, athletes had a higher diversity of gut micro-organisms, representing 22 distinct phyla, which in turn positively correlated with protein consumption and creatine kinase. CONCLUSIONS: The results provide evidence for a beneficial impact of exercise on gut microbiota diversity but also indicate that the relationship is complex and is related to accompanying dietary extremes.

Targeting the microbiota to address diet-induced obesity: a time dependent challenge.

Links between the gut microbiota and host metabolism have provided new perspectives on obesity. We previously showed that the link between the microbiota and fat deposition is age- and time-dependent subject to microbial adaptation to diet over time. We also demonstrated reduced weight gain in diet-induced obese (DIO) mice through manipulation of the gut microbiota with vancomycin or with the bacteriocin-producing probiotic Lactobacillus salivarius UCC118 (Bac(+)), with metabolic improvement achieved in DIO mice in receipt of vancomycin. However, two phases of weight gain were observed with effects most marked early in the intervention phase. Here, we compare the gut microbial populations at the early relative to the late stages of intervention using a high throughput sequencing-based analysis to understand the temporal relationship between the gut microbiota and obesity. This reveals several differences in microbiota composition over the intervening period. Vancomycin dramatically altered the gut microbiota composition, relative to controls, at the early stages of intervention after which time some recovery was evident. It was also revealed that Bac(+) treatment initially resulted in the presence of significantly higher proportions of Peptococcaceae and significantly lower proportions of Rikenellaceae and Porphyromonadaceae relative to the gut microbiota of L. salivarius UCC118 bacteriocin negative (Bac(-)) administered controls. These differences were no longer evident at the later time. The results highlight the resilience of the gut microbiota and suggest that interventions may need to be monitored and continually adjusted to ensure sustained modification of the gut microbiota.

Divergent metabolic outcomes arising from targeted manipulation of the gut microbiota in diet-induced obesity.

OBJECTIVE: The gut microbiota is an environmental regulator of fat storage and adiposity. Whether the microbiota represents a realistic therapeutic target for improving metabolic health is unclear. This study explored two antimicrobial strategies for their impact on metabolic abnormalities in murine diet-induced obesity: oral vancomycin and a bacteriocin-producing probiotic (Lactobacillus salivarius UCC118 Bac(+)). DESIGN: Male (7-week-old) C57BL/J6 mice (9-10/group) were fed a low-fat (lean) or a high-fat diet for 20 weeks with/without vancomycin by gavage at 2 mg/day, or with L. salivarius UCC118Bac(+) or the bacteriocin-negative derivative L. salivarius UCC118Bac(-) (each at a dose of 1×10(9) cfu/day by gavage). Compositional analysis of the microbiota was by 16S rDNA amplicon pyrosequencing. RESULTS: Analysis of the gut microbiota showed that vancomycin treatment led to significant reductions in the proportions of Firmicutes and Bacteroidetes and a dramatic increase in Proteobacteria, with no change in Actinobacteria. Vancomycin-treated high-fat-fed mice gained less weight over the intervention period despite similar caloric intake, and had lower fasting blood glucose, plasma TNFα and triglyceride levels compared with diet-induced obese controls. The bacteriocin-producing probiotic had no significant impact on the proportions of Firmicutes but resulted in a relative increase in Bacteroidetes and Proteobacteria and a decrease in Actinobacteria compared with the non-bacteriocin-producing control. No improvement in metabolic profiles was observed in probiotic-fed diet-induced obese mice. CONCLUSION: Both vancomycin and the bacteriocin-producing probiotic altered the gut microbiota in diet-induced obese mice, but in distinct ways. Only vancomycin treatment resulted in an improvement in the metabolic abnormalities associated with obesity thereby establishing that while the gut microbiota is a realistic therapeutic target, the specificity of the antimicrobial agent employed is critical.

Antimicrobials: Strategies for targeting obesity and metabolic health?

Obesity is associated with a number of serious health consequences, including type 2 diabetes, cardiovascular disease and a variety of cancers among others and has been repeatedly shown to be associated with a higher risk of mortality. The relatively recent discovery that the composition and metabolic activity of the gut microbiota may affect the risk of developing obesity and related disorders has led to an explosion of interest in this distinct research field. A corollary of these findings would suggest that modulation of gut microbial populations can have beneficial effects with respect to controlling obesity. In this addendum, we summarize our recent data, showing that therapeutic manipulation of the microbiota using different antimicrobial strategies may be a useful approach for the management of obesity and metabolic conditions. In addition, we will explore some of the mechanisms that may contribute to microbiota-induced susceptibility to obesity and metabolic diseases.

The Lime Tree School endeavour: healthy body, brain and heart.

Imagine what fun pupils would have at a school where the head dresses up as Dennis the Menace for World Book Day? And equally beneficial to the school, where parents can achieve a sustainable win-win by donating unwanted clothing, which is then sold to recyclers to boost school funds? These are the values that sustain Lime Tree Primary, Kingston's newest school which opened its doors in September 2012. Central to the school's ethos is the unique partnership between health and education that has transformed this fledgling primary school into a real community asset. The problem was a real one facing many local authorities today: a rising birth rate and too few classroom places; a new build seemed the obvious solution - and a real opportunity. Local children, their families, residents and professionals were interviewed and their ideas translated into proposals for the new school. A magical learning environment for local youngsters was created, embodied by the school motto, which recognises that a healthy body sustains better learning, and better learning leads to enhanced health benefits. The school lives and breathes 'Healthy Body, Brain and Heart' and transfers this into all its daily activities. And what of the future? There is no doubt that this type of initiative could be adopted in other parts of the new NHS. Wouldn't it be marvellous if other examples of like collaboration could help us jointly tackle the challenges of modern-day living?

The gut microbiota and its relationship to diet and obesity: new insights.

Obesity develops from a prolonged imbalance of energy intake and energy expenditure. However, the relatively recent discovery that the composition and function of the gut microbiota impacts on obesity has lead to an explosion of interest in what is now a distinct research field. Here, research relating to the links between the gut microbiota, diet and obesity will be reviewed under five major headings: (1) the gut microbiota of lean and obese animals, (2) the composition of the gut microbiota of lean and obese humans, (3) the impact of diet on the gut microbiota, (4) manipulating the gut microbiota and (5) the mechanisms by which the gut microbiota can impact on weight gain.

The Lime Tree School endeavour: healthy body, brain and heart.

Imagine what fun pupils would have at a school where the head dresses up as Dennis the Menace for World Book Day? And equally beneficial to the school, where parents can achieve a sustainable win-win by donating unwanted clothing, which is then sold to recyclers to boost school funds? These are the values that sustain Lime Tree Primary, Kingston's newest school which opened its doors in September 2012. Central to the school's ethos is the unique partnership between health and education that has transformed this fledgling primary school into a real community asset. The problem was a real one facing many local authorities today: a rising birth rate and too few classroom places; a new build seemed the obvious solution - and a real opportunity. Local children, their families, residents and professionals were interviewed and their ideas translated into proposals for the new school. A magical learning environment for local youngsters was created, embodied by the school motto, which recognises that a healthy body sustains better learning, and better learning leads to enhanced health benefits. The school lives and breathes 'Healthy Body, Brain and Heart' and transfers this into all its daily activities. And what of the future? There is no doubt that this type of initiative could be adopted in other parts of the new NHS. Wouldn't it be marvellous if other examples of like collaboration could help us jointly tackle the challenges of modern-day living?