Human gut microbiota (GM) includes a complex and dynamic population of microorganisms that are crucial for well‐being and survival of the organism. It has been reported as diverse and relatively ...stable with shared core microbiota, including Bacteroidetes and Firmicutes as the major dominants. They are the key regulators of body homeostasis, involving both intestinal and extra‐intestinal effects by influencing many physiological functions such as metabolism, maintenance of barrier homeostasis, inflammation and hematopoiesis. Any alteration in GM community structures not only trigger gut disorders but also influence other organs and cause associated diseases. In recent past, the GM has been defined as a ‘vital organ’ with its involvement with other organs; thus, establishing a link or a bi‐ or multidirectional communication axis between the organs via neural, endocrine, immune, humoral and metabolic pathways. Alterations in GM have been linked to several diseases known to humans; although the exact interaction mechanism between the gut and the organs is yet to be defined. In this review, the bidirectional relationship between the gut and the vital human organs was envisaged and discussed under several headings. Furthermore, several disease symptoms were also revisited to redefine the communication network between the gut microbes and the associated organs.
Significance and Impact of the Study: Gut microbiota (GM) and its metabolites play a crucial role in maintaining the health of various vital organs. Literature review and evidences suggest that any alteration in GM composition and diversity not only triggers gut disorders but also influences other organs and cause‐associated diseases. In this review, we have attempted to provide the readers a broad overview of the complex role of GM and its vital connection with other human organs. Our effort will foster the development of personalized treatment that can be adopted and evolved by targeting the microbiome in a deliberately controlled manner.
Hormones control the major biological functions of stress response, growth, metabolism, and reproduction. In animals, these hormones show pronounced seasonality, with different set-points for ...different seasons. In humans, the seasonality of these hormones remains unclear, due to a lack of datasets large enough to discern common patterns and cover all hormones. Here, we analyze an Israeli health record on 46 million person-years, including millions of hormone blood tests. We find clear seasonal patterns: The effector hormones peak in winter-spring, whereas most of their upstream regulating pituitary hormones peak only months later, in summer. This delay of months is unexpected because known delays in the hormone circuits last hours. We explain the precise delays and amplitudes by proposing and testing a mechanism for the circannual clock: The gland masses grow with a timescale of months due to trophic effects of the hormones, generating a feedback circuit with a natural frequency of about a year that can entrain to the seasons. Thus, humans may show coordinated seasonal set-points with a winter-spring peak in the growth, stress, metabolism, and reproduction axes.
Gonadal hormones play a key role in the establishment, activation, and regulation of the hypothalamic-pituitary-adrenal (HPA) axis. By influencing the response and sensitivity to releasing factors, ...neurotransmitters, and hormones, gonadal steroids help orchestrate the gain of the HPA axis to fine-tune the levels of stress hormones in the general circulation. From early life to adulthood, gonadal steroids can differentially affect the HPA axis, resulting in sex differences in the responsivity of this axis. The HPA axis influences many physiological functions making an organism's response to changes in the environment appropriate for its reproductive status. Although the acute HPA response to stressors is a beneficial response, constant activation of this circuitry by chronic or traumatic stressful episodes may lead to a dysregulation of the HPA axis and cause pathology. Compared to males, female mice and rats show a more robust HPA axis response, as a result of circulating estradiol levels which elevate stress hormone levels during non-threatening situations, and during and after stressors. Fluctuating levels of gonadal steroids in females across the estrous cycle are a major factor contributing to sex differences in the robustness of HPA activity in females compared to males. Moreover, gonadal steroids may also contribute to epigenetic and organizational influences on the HPA axis even before puberty. Correspondingly, crosstalk between the hypothalamic-pituitary-gonadal (HPG) and HPA axes could lead to abnormalities of stress responses. In humans, a dysregulated stress response is one of the most common symptoms seen across many neuropsychiatric disorders, and as a result, such interactions may exacerbate peripheral pathologies. In this review, we discuss the HPA and HPG axes and review how gonadal steroids interact with the HPA axis to regulate the stress circuitry during all stages in life.
Stress is recognized as an important issue in basic and clinical neuroscience research, based upon the founding historical studies by Walter Canon and Hans Selye in the past century, when the concept ...of stress emerged in a biological and adaptive perspective. A lot of research after that period has expanded the knowledge in the stress field. Since then, it was discovered that the response to stressful stimuli is elaborated and triggered by the, now known,
, which integrates a wide diversity of brain structures that, collectively, are able to detect events and interpret them as real or potential threats. However, different types of stressors engage different brain networks, requiring a fine-tuned functional neuroanatomical processing. This integration of information from the stressor itself may result in a rapid activation of the Sympathetic-Adreno-Medullar (SAM) axis and the Hypothalamus-Pituitary-Adrenal (HPA) axis, the two major components involved in the stress response. The complexity of the stress response is not restricted to neuroanatomy or to SAM and HPA axes mediators, but also diverge according to timing and duration of stressor exposure, as well as its short- and/or long-term consequences. The identification of neuronal circuits of stress, as well as their interaction with mediator molecules over time is critical, not only for understanding the physiological stress responses, but also to understand their implications on mental health.
The highest density of microbes resides in human gastrointestinal tract, known as “Gut microbiome”. Of note, the members of the genus
Lactobacillus
that belong to phyla Firmicutes are the most ...important probiotic bacteria of the gut microbiome. These gut-residing
Lactobacillus
species not only communicate with each other but also with the gut epithelial lining to balance the gut barrier integrity, mucosal barrier defence and ameliorate the host immune responses. The human body suffers from several inflammatory diseases affecting the gut, lungs, heart, bone or neural tissues. Mounting evidence supports the significant role of
Lactobacillus
spp. and their components (such as metabolites, peptidoglycans, and/or surface proteins) in modulatingimmune responses, primarily through exchange of immunological signals between gastrointestinal tract and distant organs. This bidirectional crosstalk which is mediated by
Lactobacillus
spp. promotes anti-inflammatory response, thereby supporting the improvement of symptoms pertaining to asthma, chronic obstructive pulmonary disease (COPD), neuroinflammatory diseases (such as multiple sclerosis, alzheimer’s disease, parkinson’s disease), cardiovascular diseases, inflammatory bowel disease (IBD) and chronic infections in patients. The metabolic disorders, obesity and diabetes are characterized by a low-grade inflammation. Genus
Lactobacillus
alleviates metabolic disorders by regulating the oxidative stress response and inflammatory pathways. Osteoporosis is also associated with bone inflammation and resorption. The
Lactobacillus
spp. and their metabolites act as powerful immune cell controllers and exhibit a regulatory role in bone resorption and formation, supporting bone health. Thus, this review demonstrated the mechanisms and summarized the evidence of the benefit of
Lactobacillus
spp. in alleviating inflammatory diseases pertaining to different organs from animal and clinical trials. The present narrative review explores in detail the complex interactions between the gut-dwelling
Lactobacillus
spp. and the immune components in distant organs to promote host’s health.
The human intestinal microbiome substantially affects human health and resistance to infections in its dynamic composition and varying release of microbial-derived metabolites. Short-chain fatty ...acids (SCFA) produced by commensal bacteria through fermentation of indigestible fibres are considered key regulators in orchestrating the host immune response to microbial colonization by regulating phagocytosis, chemokine and central signalling pathways of cell growth and apoptosis, thereby shaping the composition and functionality of the intestinal epithelial barrier. Although research of the last decades provided valuable insight into the pleiotropic functions of SCFAs and their capability to maintain human health, mechanistic details on how SCFAs act across different cell types and other organs are not fully understood. In this review, we provide an overview of the various functions of SCFAs in regulating cellular metabolism, emphasizing the orchestration of the immune response along the gut-brain, the gut-lung and the gut-liver axes. We discuss their potential pharmacological use in inflammatory diseases and infections and highlight new options of relevant human three-dimensional organ models to investigate and validate their biological functions in more detail.
The influences of different axes on the accuracy of a machine tool vary due to their positions in the structure of the machine tool and their local errors. In this paper, geometric error contribution ...modeling and a sensitivity evaluation of the axes of a machine tool are proposed to obtain the influences of each axis and determine the crucial axes of the machine tool. First, the error vector components of the position-independent errors are obtained by product of exponential (POE) theory. Second, the error contributions of all axes are established based on transforming differential changes between coordinate frames by using the POE formula of the tool relative to each axis and the error vectors of the axes. Third, an error sensitivity matrix of each axis is established according to the formula of error contribution about the error vector of the axis. Fourth, two methods are proposed for an error sensitivity evaluation of the axes to determine the crucial axes: one method employs the weights of the error contributions of the axes, and the other method employs the error sensitivity coefficients of the axes. Finally, simulations and real cutting experiments are carried out with the SmartCNC500_DRTD five-axis machine tool to verify the effectiveness of the error contribution modeling and error sensitivity evaluation of the axis.
•The influences and error vector of position-independent errors are developed.•Error contribution of each axis on the integrated errors of the machine tool are obtained.•Error sensitivity matrix of all axes are established including tool position and tool orientation.•Error sensitivity evaluation of the axis is proposed with two methods.•The crucial axes of the machine tool are obtained.
Display omitted
•The data-driven compensation method of the 5-axis machine tools is proposed.•The relationship between the thermal error and positioning error is explored. A novel thermal error is ...proposed for feed drive systems.•The regression analysis is effective to establish the thermal error model.•The pre-stretch can improve the positioning accuracy.
The data-driven thermal error compensation method of high-speed and precision five-axis machine tools was proposed based on the homogeneous transformation. The compensation component was obtained by analyzing the error transmission chain of machine tools and was expressed as the transmission matrix consisting of thermal error terms of linear axes and spindle system according to the differential movement of the compensation axis. From the view of thermal error generation mechanism, the thermal error of the linear axis was formulated as the product of the polynomial function with time as its independent variable and the polynomial function with position as its independent variable. Then the thermal errors of the linear axes were decomposed and identified from the measured positioning error. The thermal error of the spindle system was identified by the thermal characteristic experiments. The compensation component in each direction is calculated by substituting the identified thermal error terms of the linear axes and spindle system into the data-driven thermal error model. Finally, to demonstrate the effectiveness of the proposed method, the thermal error at a new working condition was predicted, and then the error compensation and actual machining were carried out. The results show that the machining error is reduced by more than 85% and 37% with the present error compensation compared with that without compensation and that without traditional error compensation, respectively. This research sheds new light on both the generation mechanism and the compensation method of the thermally-induced error of five-axis machine tools.
The relationship between gut microbiota and neurological diseases, including chronic pain, has received increasing attention. The gut microbiome is a crucial modulator of visceral pain, whereas ...recent evidence suggests that gut microbiota may also play a critical role in many other types of chronic pain, including inflammatory pain, headache, neuropathic pain, and opioid tolerance. We present a narrative review of the current understanding on the role of gut microbiota in pain regulation and discuss the possibility of targeting gut microbiota for the management of chronic pain. Numerous signalling molecules derived from gut microbiota, such as by-products of microbiota, metabolites, neurotransmitters, and neuromodulators, act on their receptors and remarkably regulate the peripheral and central sensitisation, which in turn mediate the development of chronic pain. Gut microbiota-derived mediators serve as critical modulators for the induction of peripheral sensitisation, directly or indirectly regulating the excitability of primary nociceptive neurones. In the central nervous system, gut microbiota-derived mediators may regulate neuroinflammation, which involves the activation of cells in the blood–brain barrier, microglia, and infiltrating immune cells, to modulate induction and maintenance of central sensitisation. Thus, we propose that gut microbiota regulates pain in the peripheral and central nervous system, and targeting gut microbiota by diet and pharmabiotic intervention may represent a new therapeutic strategy for the management of chronic pain.
PDF
