Joe Alcock

Is eating behavior manipulated by the gastrointestinal microbiota? Evolutionary pressures and potential mechanisms

Microbes in the gastrointestinal tract are under selective pressure to manipulate host eating behavior to increase their fitness, sometimes at the expense of host fitness. Microbes may do this through two potential strategies: (i) generating cravings for foods that they specialize on or foods that suppress their competitors, or (ii) inducing dysphoria until we eat foods that enhance their fitness. We review several potential mechanisms for microbial control over eating behavior including microbial influence on reward and satiety pathways, production of toxins that alter mood, changes to receptors including taste receptors, and hijacking of the vagus nerve, the neural axis between the gut and the brain. We also review the evidence for alternative explanations for cravings and unhealthy eating behavior. Because microbiota are easily manipulatable by prebiotics, probiotics, antibiotics, fecal transplants, and dietary changes, altering our microbiota offers a tractable approach to otherwise intractable problems of obesity and unhealthy eating.

Turning Up The Heat: Immune Brinksmanship In The Acute-phase Response

The acute-phase response (APR) is a systemic response to severe trauma, infection, and cancer, although many of the numerous cytokine-mediated components of the APR are incompletely understood. Some of these components, such as fever, reduced availability of iron and zinc, and nutritional restriction due to anorexia, appear to be stressors capable of causing harm to both the pathogen and the host. We review how the host benefits from differences in susceptibility to stress between pathogens and the host. Pathogens, infected host cells, and neoplastic cells are generally more stressed or vulnerable to additional stress than the host because: a) targeted local inflammation works in synergy with APR stressors; b) proliferation/growth increases vulnerability to stress; c) altered pathogen physiology results in pathogen stress or vulnerability; and d) protective heat shock responses are partially abrogated in pathogens since their responses are utilized by the host to enhance immune responses. Therefore, the host utilizes a coordinated system of endogenous stressors to provide additional levels of defense against pathogens. This model of immune brinksmanship can explain the evolutionary basis for the mutually stressful components of the APR.

Test–retest reliability of multidimensional dyspnea profile recall ratings in the emergency department: a prospective, longitudinal study

BackgroundDyspnea is among the most common reasons for emergency department (ED) visits by patients with cardiopulmonary disease who are commonly asked to recall the symptoms that prompted them to come to the ED. The reliability of recalled dyspnea has not been systematically investigated in ED patients.MethodsPatients with chronic or acute cardiopulmonary conditions who came to the ED with dyspnea (N = 154) completed the Multidimensional Dyspnea Profile (MDP) several times during the visit and in a follow-up visit 4 to 6 weeks later (n = 68). The MDP has 12 items with numerical ratings of intensity, unpleasantness, sensory qualities, and emotions associated with how breathing felt when participants decided to come to the ED (recall MDP) or at the time of administration (“now” MDP). The recall MDP was administered twice in the ED and once during the follow-up visit. Principal components analysis (PCA) with varimax rotation was used to assess domain structure of the recall MDP. Internal consistency reliability was assessed with Cronbach’s alpha. Test–retest reliability was assessed with intraclass correlation coefficients (ICCs) for absolute agreement for individual items and domains.ResultsPCA of the recall MDP was consistent with two domains (Immediate Perception, 7 items, Cronbach’s alpha = .89 to .94; Emotional Response, 5 items; Cronbach’s alpha = .81 to .85). Test–retest ICCs for the recall MDP during the ED visit ranged from .70 to .87 for individual items and were .93 and .94 for the Immediate Perception and Emotional Response domains. ICCs were much lower for the interval between the ED visit and follow-up, both for individual items (.28 to .66) and for the Immediate Perception and Emotional Response domains (.72 and .78, respectively).ConclusionsDuring an ED visit, recall MDP ratings of dyspnea at the time participants decided to seek care in the ED are reliable and sufficiently stable, both for individual items and the two domains, that a time lag between arrival and questionnaire administration does not critically affect recall of perceptual and emotional characteristics immediately prior to the visit. However, test–retest reliability of recall over a 4- to 6-week interval is poor for individual items and significantly attenuated for the two domains.

Laboratory personnel gender and cold pressor apparatus affect subjective pain reports

BACKGROUND There is no standardized method for cold pressor pain tasks across experiments. Temperature, apparatus and aspects of experimenters vary widely among studies. It is well known that experimental pain tolerance is influenced by setting as well as the sex of the experimenter. It is not known whether other contextual factors influence experimental pain reporting. OBJECTIVES The present two-part experiment examines whether minimizing and standardizing interactions with laboratory personnel (eg, limiting interaction with participants to consenting and questions and not during the actual pain task) eliminates the influence of examiner characteristics on subjective pain reports and whether using different cold pain apparatus (cooler versus machine) influences reports. METHODS The present experiment manipulated the gender of the experimenter (male, female and transgender) and the type of cold pressor task (CPT) apparatus (ice cooler versus refrigerated bath circulator). Participants conducted the CPT at one of two pain levels (5°C or 16°C) without an experimenter present. RESULTS Men and women showed lower pain sensitivity when they were processed by biological male personnel than by biological female personnel before the CPT. Women who interacted with a transgendered researcher likewise reported higher pain sensitivity than women processed by biological male or female researchers. The type of CPT apparatus, despite operating at equivalent temperatures, also influenced subjective pain reports. DISCUSSION The findings show that even minimal interactions with laboratory personnel who differ in gender, and differences in laboratory materials impact the reliable measurement of pain. CONCLUSION More standardized protocols for measuring pain across varying research and clinical settings should be developed.

Tough guys or sensitive guys? Disentangling the role of examiner sex on patient pain reports.

BACKGROUND Experimental and clinical pain studies are conflicting regarding whether individuals report heightened or dampened pain sensitivity in the presence of other men or women. OBJECTIVES In the present preliminary study, two small medical record reviews of patients admitted for emergency care were conducted to examine the possibility that patients may report differential pain intensity to male and female health care examiners. The study also sought to determine whether these effects are moderated by and, thus, only detectable by examining patients at different pain (debilitation) levels. METHODS Pain intensity scores were extracted from two medical record reviews of patients admitted for emergency care (n=64 and n=135, respectively). Pain intensity was measured using an 11-point numerical scale during standard triage assessments and the sex of the examiner was recorded. RESULTS Mean pain scores reported to male and female emergency staff did not differ in either set of medical records. However, when patients were split between low and high pain levels, male patients reported higher pain scores to male practitioners when experiencing relatively low pain levels, and both male and female patients reported higher pain scores to female practitioners when experiencing relatively high pain levels. DISCUSSION The statistical magnitudes of these effects were large, suggesting that this phenomenon may be a pervasive feature in clinical settings and experimental pain studies. CONCLUSION These preliminary findings warrant larger-scale investigations of social contextual influences on patient pain reports, which are necessary for creating more standardized protocols for reliably assessing and treating patient pain experiences.

Nutrient Signaling: Evolutionary Origins of the Immune-Modulating Effects of Dietary Fat

Many dietary fatty acids (FA) have potent effects on inflammation, which is not only energetically costly, but also contributes to a range of chronic diseases. This presents an evolutionary paradox: Why should the host initiate a costly and damaging response to commonly encountered nutrients? We propose that the immune system has evolved a capacity to modify expenditure on inflammation to compensate for the effects of dietary FA on gut microorganisms. In a comprehensive literature review, we show that the body preferentially upregulates inflammation in response to saturated FA that promote harmful microbes. In contrast, the host often reduces inflammation in response to the many unsaturated FA with antimicrobial properties. Our model is supported by contrasts involving shorter-chain FA and omega-3 FA, but with less consistent evidence for trans fats, which are a recent addition to the human diet. Our findings support the idea that the vertebrate immune system has evolved a capacity to detect diet-driven shifts in the composition of gut microbiota from the profile of FA consumed, and to calibrate the costs of inflammation in response to these cues. We conclude by extending the nutrient signaling model to other nutrients, and consider implications for drug discovery and public health.

A Clinical Perspective in Evolutionary Medicine: What We Wish We Had Learned in Medical School

Medical students have much to gain by understanding how evolutionary principles affect human health and disease. Many theoretical and experimental studies have applied lessons from evolutionary biology to issues of critical importance to medical science. A firm grasp of evolution and natural selection is required to understand why the human body remains vulnerable to many diseases. Although we often integrate evolutionary concepts when we teach medical students and residents, the vast majority of medical students never receive any instruction on evolution. As a result, many trainees lack the tools to understand key advances and miss valuable opportunities for education and research. Here, we outline some of the evolutionary principles that we wished we had learned during our medical training.

Sulfate-reducing bacteria impairs working memory in mice.

The ability of gut microbes to bi-directionally communicate with the brain and vice versa form the basis of the gut microbiome-central nervous system axis. It has been shown that inoculation with pathogenic gut bacteria alters the behavior of mice; however, it is not known whether or not non-pathogenic resident microbes have similar effects. In this study, we tested the hypothesis that the administration of sulfate-reducing bacteria (SRB), a specific group of resident gut bacteria that generate hydrogen sulfide (H2S), impair learning and memory performance in mice tested in an 8-arm radial maze and Morris water maze. We found that mice spent more time in the center of the maze when they were gavaged with live SRB as compared to mice given saline (control), lactulose+mannitol (L/M), or killed SRB. SRB-gavaged mice were also tested using the Morris water maze and were found to take longer to complete the test, spend more time further from the platform, and have a longer path length to reach the platform. This effect of SRB on maze performance was associated with a higher concentration of H2S in the small intestine and cecum. We conclude that SRB, a specific resident gut bacterial species, could impair cognitive function in mice.

Fatty acids from diet and microbiota regulate energy metabolism

A high-fat diet and elevated levels of free fatty acids are known risk factors for metabolic syndrome, insulin resistance, and visceral obesity. Although these disease associations are well established, it is unclear how different dietary fats change the risk of insulin resistance and metabolic syndrome. Here, we review emerging evidence that insulin resistance and fat storage are linked to changes in the gut microbiota. The gut microbiota and intestinal barrier function, in turn, are highly influenced by the composition of fat in the diet. We review findings that certain fats (for example, long-chain saturated fatty acids) are associated with dysbiosis, impairment of intestinal barrier function, and metabolic endotoxemia. In contrast, other fatty acids, including short-chain and certain unsaturated fatty acids, protect against dysbiosis and impairment of barrier function caused by other dietary fats. These fats may promote insulin sensitivity by inhibiting metabolic endotoxemia and dysbiosis-driven inflammation. During dysbiosis, the modulation of metabolism by diet and microbiota may represent an adaptive process that compensates for the increased fuel demands of an activated immune system.

Resource conflict and cooperation between human host and gut microbiota: implications for nutrition and health

Diet has been known to play an important role in human health since at least the time period of the ancient Greek physician Hippocrates. In the last decade, research has revealed that microorganisms inhabiting the digestive tract, known as the gut microbiota, are critical factors in human health. This paper draws on concepts of cooperation and conflict from ecology and evolutionary biology to make predictions about host–microbiota interactions involving nutrients. To optimally extract energy from some resources (e.g., fiber), hosts require cooperation from microbes. Other nutrients can be utilized by both hosts and microbes (e.g., simple sugars, iron) in their ingested form, which may lead to greater conflict over these resources. This framework predicts that some negative health effects of foods are driven by the direct effects of these foods on human physiology and by indirect effects resulting from microbiome–host competition and conflict (e.g., increased invasiveness and inflammation). Similarly, beneficial effects of some foods on host health may be enhanced by resource sharing and other cooperative behaviors between host and microbes that may downregulate inflammation and virulence. Given that some foods cultivate cooperation between hosts and microbes while others agitate conflict, host–microbe interactions may be novel targets for interventions aimed at improving nutrition and human health.