Special series on the role of the microbiome in reproduction and fertility.

Many parts of the animal and human body host groups of bacteria, viruses, and fungi that together are known as the microbiome. Microbiomes do not cause disease but are important for the healthy working of many systems in the body, including for reproduction and fertility. While the microbiome that lives in a reproductive tract play the most direct role, microbiomes from other areas of the body may also affect reproductive health. However, not much is known about how these groups of microorganisms regulate fertility as well as the health of parents and offspring and help animals to cope with environmental changes. Furthermore, compared to the large amount of research in laboratory species and humans, there is less information about domestic or wild animal species. This special series of Reproduction and Fertility on microbiomes is aimed at filling this gap with articles from experts highlighting important evidence in reproductive microbiomes, current research gaps, and new directions.

Accuracy of Point-of-Care-Ultrasonography in Confirming Shoulder Reduction in Emergency Departments.

Aims Accurate identification of the successful reduction of a dislocated shoulder could avoid additional episodes of procedural sedation and repeated performance of X-rays. The objective of this study was to assess the diagnostic accuracy of point-of-care-ultrasound (POCUS) in the confirmation of a successful joint reduction in patients with shoulder dislocation. Methods This was a single-centre, prospective observational study set in an urban academic ED in Ireland, with a convenience sample of adult patients with shoulder dislocation on X-ray. Ultrasound was performed on participants before and after joint reduction using a posterior approach technique. The operator's confidence levels were recorded after image acquisition. Results Thirty-three subjects were recruited. All dislocations were correctly identified on pre-reduction US, indicating a sensitivity of 100% (CI 89.42 - 100). Post-reduction US confirmed successful reduction in 30 subjects that were subsequently reported as such on X-Ray, giving it a specificity of 100% (CI 88.43 - 100). Failure to achieve reduction was correctly identified on US in three cases, resulting in post-reduction US Sensitivity of 100% (CI 29.24 - 100) and 100% accuracy (CI 89.42 - 100). Conclusion This study has shown that POCUS, with a posterior approach technique, has 100% sensitivity and specificity in confirming successful shoulder reduction in the ED.

The antimicrobial capacity of embalming solutions: a comparative study.

AIMS: Infectious health risks are associated with handling human cadavers and to decrease such risks, cadavers are embalmed using different chemicals. The aim of this study is to quantify the amount of micro-organisms present in different regions of human cadavers before embalming, after embalming and over a period of 8 months. METHODS AND RESULTS: Human cadavers were embalmed using Thiel, formalin, Genelyn and the Imperial College London soft-preservation (ICL-SP) solution with two cadavers per technique. Sterile swabs were used to collect samples from different regions. Samples were collected every 2 months. All cadavers had a high number of microbial colonies before embalming. While no colonies were detected on formalin and Genelyn embalmed cadavers post-embalming, the number of colonies decreased significantly in Thiel-embalmed cadavers and stayed relatively the same in ICL-SP-embalmed cadavers. CONCLUSIONS: Formalin-embalmed cadavers showed the strongest disinfecting abilities followed by Thiel-embalmed cadavers, then Genelyn-embalmed cadavers and finally by ICL-SP cadavers. SIGNIFICANCE AND IMPACT OF THE STUDY: This study highlights how under researched this area is and the evident variation in the antimicrobial abilities of different embalming solutions on the cadaver as a whole and within different regions of the same cadaver.

"That's His Choice Not Mine!" Parents' Perspectives on Providing a Packed Lunch for Their Children in Primary School.

OBJECTIVE: To examine factors influencing parents' selection of packed lunches over a school lunch, their choices in food preparation, and the role of children within these. DESIGN: A qualitative approach using semistructured focus group and individual interviews. SETTING: Four primary schools in a UK local authority. PARTICIPANTS: Twenty parents providing a packed lunch for their children (aged 5-11 years). ANALYSIS: An inductive thematic approach was used to identify categories and themes. The researchers maintained rigor in the data analysis through internal discussion and review until consensus was reached. RESULTS: Children emerged as active decision makers exerting substantial power particularly in the initial decision to have a packed lunch, and then in influencing the lunch's contents. The packed lunch could be a source of anxiety for some parents; however, ultimately parents' attitudes and perceptions revolved around the key requirement that the lunch was eaten. Providing a packed lunch was a means of achieving this. CONCLUSIONS: This study highlights children's growing authority over everyday food decisions. Further research is needed to explore children's perceptions of their role in food provision. The study's findings have implications for school food, nutrition education, and school-based interventions. Frameworks that look to improve children's nutrition in this area should reflect children's growing status as food decision makers and consider how this can be employed to support and sustain positive changes.

Steroids, stress and the gut microbiome-brain axis.

It is becoming well established that the gut microbiome has a profound impact on human health and disease. In this review, we explore how steroids can influence the gut microbiota and, in turn, how the gut microbiota can influence hormone levels. Within the context of the gut microbiome-brain axis, we discuss how perturbations in the gut microbiota can alter the stress axis and behaviour. In addition, human studies on the possible role of gut microbiota in depression and anxiety are examined. Finally, we present some of the challenges and important questions that need to be addressed by future research in this exciting new area at the intersection of steroids, stress, gut-brain axis and human health.

Medicine and the McNamara fallacy.

The 'McNamara fallacy' (also known as quantitative fallacy) is named after the US Secretary of Defense during the Vietnam War. The fallacy consists of over-reliance on metrics, and may be summarised as: 'if it cannot be measured, it is not important'. This paper describes the McNamara fallacy as it applies to medicine and healthcare, taking as examples hospital mortality data, NHS targets and quality assurance.

Early-life adversity and brain development: Is the microbiome a missing piece of the puzzle?

The prenatal and postnatal early-life periods are both dynamic and vulnerable windows for brain development. During these important neurodevelopmental phases, essential processes and structures are established. Exposure to adverse events that interfere with this critical sequence of events confers a high risk for the subsequent emergence of mental illness later in life. It is increasingly accepted that the gastrointestinal microbiota contributes substantially to shaping the development of the central nervous system. Conversely, several studies have shown that early-life events can also impact on this gut community. Due to the bidirectional communication between the gut and the brain, it is possible that aberrant situations affecting either organ in early life can impact on the other. Studies have now shown that deviations from the gold standard trajectory of gut microbiota establishment and development in early life can lead not only to disorders of the gastrointestinal tract but also complex metabolic and immune disorders. These are being extended to disorders of the central nervous system and understanding how the gut microbiome shapes brain and behavior during early life is an important new frontier in neuroscience.

Medical Nemesis 40 years on: the enduring legacy of Ivan Illich.

Ivan Illich's attack on modern medicine, Medical Nemesis, appeared in 1974. The book famously opened with the statement: 'The medical establishment has become a major threat to health.' Forty years after its publication, this paper examines the major themes of the book, and asks whether events since its publication have added weight to Illich's thesis.

Early-life stress selectively affects gastrointestinal but not behavioral responses in a genetic model of brain-gut axis dysfunction.

BACKGROUND: Early-life stress and a genetic predisposition to display an anxiety- and depressive-like phenotype are associated with behavioral and gastrointestinal (GI) dysfunction. Animals exposed to early-life stress, and those genetically predisposed to display anxiety or depressive behaviors, have proven useful tools in which to study stress-related GI disorders, such as irritable bowel syndrome (IBS). IBS is a heterogeneous disorder, and likely a consequence of both genetic and environmental factors. However, the combined effects of early-life stress and a genetic predisposition to display anxiety- and depression-like behaviors on GI function have not been investigated. METHODS: We assessed the effect of maternal separation (MS) on behavioral and GI responses in WKY animals relative to a normo-anxious reference strain. KEY RESULTS: Both non-separated (NS) WKY and WKY-MS animals displayed anxiety-like responses in the open-field test and depressive-like behaviors in the forced swim test relative to Sprague-Dawley rats. However, MS had no further influence on anxiety- and depressive-like behaviors exhibited by this stress-prone rat strain. Similarly, corticosterone levels measured after the OFT were insensitive to MS in WKY animals. However, WKY-MS displayed significantly increased colonic visceral hypersensitivity, fecal output, and altered colonic cholinergic sensitivity. CONCLUSIONS & INFERENCES: Our data suggest that early-life stress, on the background of a genetic predisposition to display an anxiety- and depressive-like phenotype, selectively influences GI function rather than stress-related behaviors. Thus, our findings highlight the importance of genetic predisposition on the outcome of early-life adversity on GI function.

John Bradshaw (1918-1989): putting doctors on trial.

John S. Bradshaw (1918-1989) qualified as a doctor, but spent most of his professional life as a writer and journalist. His best-known work, Doctors on Trial (1978), a polemical book which attacked modern medicine, concluded that "western doctors today are certainly more productive, directly or indirectly, of ill-health, in every sense, than of health". This book was partly inspired by the writings of Ivan Illich, the Austrian priest and social philosopher. This article examines Bradshaw's life and the influence of Illich's thinking on Doctors on Trial.

Serotonin, tryptophan metabolism and the brain-gut-microbiome axis.

The brain-gut axis is a bidirectional communication system between the central nervous system and the gastrointestinal tract. Serotonin functions as a key neurotransmitter at both terminals of this network. Accumulating evidence points to a critical role for the gut microbiome in regulating normal functioning of this axis. In particular, it is becoming clear that the microbial influence on tryptophan metabolism and the serotonergic system may be an important node in such regulation. There is also substantial overlap between behaviours influenced by the gut microbiota and those which rely on intact serotonergic neurotransmission. The developing serotonergic system may be vulnerable to differential microbial colonisation patterns prior to the emergence of a stable adult-like gut microbiota. At the other extreme of life, the decreased diversity and stability of the gut microbiota may dictate serotonin-related health problems in the elderly. The mechanisms underpinning this crosstalk require further elaboration but may be related to the ability of the gut microbiota to control host tryptophan metabolism along the kynurenine pathway, thereby simultaneously reducing the fraction available for serotonin synthesis and increasing the production of neuroactive metabolites. The enzymes of this pathway are immune and stress-responsive, both systems which buttress the brain-gut axis. In addition, there are neural processes in the gastrointestinal tract which can be influenced by local alterations in serotonin concentrations with subsequent relay of signals along the scaffolding of the brain-gut axis to influence CNS neurotransmission. Therapeutic targeting of the gut microbiota might be a viable treatment strategy for serotonin-related brain-gut axis disorders.

Disturbance of the gut microbiota in early-life selectively affects visceral pain in adulthood without impacting cognitive or anxiety-related behaviors in male rats.

Disruption of bacterial colonization during the early postnatal period is increasingly being linked to adverse health outcomes. Indeed, there is a growing appreciation that the gut microbiota plays a role in neurodevelopment. However, there is a paucity of information on the consequences of early-life manipulations of the gut microbiota on behavior. To this end we administered an antibiotic (vancomycin) from postnatal days 4-13 to male rat pups and assessed behavioral and physiological measures across all aspects of the brain-gut axis. In addition, we sought to confirm and expand the effects of early-life antibiotic treatment using a different antibiotic strategy (a cocktail of pimaricin, bacitracin, neomycin; orally) during the same time period in both female and male rat pups. Vancomycin significantly altered the microbiota, which was restored to control levels by 8 weeks of age. Notably, vancomycin-treated animals displayed visceral hypersensitivity in adulthood without any significant effect on anxiety responses as assessed in the elevated plus maze or open field tests. Moreover, cognitive performance in the Morris water maze was not affected by early-life dysbiosis. Immune and stress-related physiological responses were equally unaffected. The early-life antibiotic-induced visceral hypersensitivity was also observed in male rats given the antibiotic cocktail. Both treatments did not alter visceral pain perception in female rats. Changes in visceral pain perception in males were paralleled by distinct decreases in the transient receptor potential cation channel subfamily V member 1, the α-2A adrenergic receptor and cholecystokinin B receptor. In conclusion, a temporary disruption of the gut microbiota in early-life results in very specific and long-lasting changes in visceral sensitivity in male rats, a hallmark of stress-related functional disorders of the brain-gut axis such as irritable bowel disorder.

Priming for health: gut microbiota acquired in early life regulates physiology, brain and behaviour.

UNLABELLED: The infant gut microbiome is dynamic, and radical shifts in composition occur during the first 3 years of life. Disruption of these developmental patterns, and the impact of the microbial composition of our gut on brain and behaviour, has attracted much recent attention. Integrating these observations is an important new research frontier. CONCLUSION: Early-life perturbations of the developing gut microbiota can impact on the central nervous system and potentially lead to adverse mental health outcomes.

Differential activation of the prefrontal cortex and amygdala following psychological stress and colorectal distension in the maternally separated rat.

Visceral hypersensitivity is a hallmark of many clinical conditions and remains an ongoing medical challenge. Although the central neural mechanisms that regulate visceral hypersensitivity are incompletely understood, it has been suggested that stress and anxiety often act as initiating or exacerbating factors. Dysfunctional corticolimbic structures have been implicated in disorders of visceral hypersensitivity such as irritable bowel syndrome (IBS). Moreover, the pattern of altered physiological responses to psychological and visceral stressors reported in IBS patients is also observed in the maternally separated (MS) rat model of IBS. However, the relative contribution of various divisions within the cortex to the altered stress responsivity of MS rats remains unknown. The aim of this study was to analyze the cellular activation pattern of the prefrontal cortex and amygdala in response to an acute psychological stressor (open field) and colorectal distension (CRD) using c-fos immunohistochemistry. Several corticoamygdalar structures were analyzed for the presence of c-fos-positive immunoreactivity including the prelimbic cortex, infralimbic cortex, the anterior cingulate cortex (both rostral and caudal) and the amygdala. Our data demonstrate distinct activation patterns within these corticoamygdalar regions including differential activation in basolateral versus central amygdala following exposure to CRD but not the open field stress. The identification of this neuronal activation pattern may provide further insight into the neurochemical pathways through which therapeutic strategies for IBS could be derived.

Antipsychotics and the gut microbiome: olanzapine-induced metabolic dysfunction is attenuated by antibiotic administration in the rat.

The atypical antipsychotic olanzapine is often associated with serious metabolic side effects including weight gain and increased visceral fat. These adverse events are a considerable clinical problem and the mechanisms underlying them are multifactorial and poorly understood. Growing evidence suggests that the gut microbiota has a key role in energy regulation and disease states such as obesity. Moreover, we recently showed that chronic olanzapine altered the composition of the gut microbiome in the rat. It is thus possible that treatments that alter gut microbiota composition could ameliorate olanzapine-induced weight gain and associated metabolic syndrome. To this end, we investigated the impact of antibiotic-induced alteration of the gut microbiota on the metabolic effects associated with chronic olanzapine treatment in female rats. Animals received vehicle or olanzapine (2 mg kg(-1) per day) for 21 days, intraperitoneal injection, two times daily. Animals were also coadministered vehicle or an antibiotic cocktail consisting of neomycin (250 mg kg(-1) per day), metronidazole (50 mg kg(-1) per day) and polymyxin B (9 mg kg(-1) per day) by oral gavage, daily, beginning 5 days before olanzapine treatment. The antibiotic cocktail drastically altered the microbiota of olanzapine-treated rats, and olanzapine alone was also associated with an altered microbiota. Coadministration of the antibiotic cocktail in olanzapine-treated rats attenuated: body weight gain, uterine fat deposition, macrophage infiltration of adipose tissue, plasma free fatty acid levels, all of which were increased by olanzapine alone. These results suggest that the gut microbiome has a role in the cycle of metabolic dysfunction associated with olanzapine, and could represent a novel therapeutic target for preventing antipsychotic-induced metabolic disease.