In humans, the intestine is the major reservoir of microbes. Although the intestinal microbial community exists in a state of homeostasis called eubiosis, environmental and genetics factors can lead to microbial perturbation or dysbiosis, a state associated with various pathologies including inflammatory bowel diseases (IBD) and colorectal cancer (CRC). Dysbiotic microbiota is thought to contribute to the initiation and progression of CRC. At the opposite end of the spectrum, two recently published studies inSciencereveal that the microbiota is essential for chemotherapeutic (...) drug efficacy, suggesting a beneficial microbial function in cancer management. The dichotomy between the beneficial and detrimental roles of the microbiota during cancer initiation, progression, and treatment emphasize the interwoven relationship between bacteria and cancer. Moreover, these findings suggest that the microbiota could be considered as a therapeutic target, not only at the level of cancer prevention, but also during management, i.e. by enhancing the efficacy of chemotherapeutics. (shrink)

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. (shrink)

We propose the “microbiota‐inflammasome” hypothesis of major depressive disorder (MDD, a mental illness affecting the way a person feels and thinks, characterized by long‐lasting feelings of sadness). We hypothesize that pathological shifts in gut microbiota composition (dysbiosis) caused by stress and gut conditions result in the upregulation of pro‐inflammatory pathways mediated by the Nod‐like receptors family pyrin domain containing 3 (NLRP3) inflammasome (an intracellular platform involved in the activation of inflammatory processes). This upregulation exacerbates depressive symptomatology and further compounds gut (...) dysbiosis. In this review we describe MDD/chronic stress‐induced changes in: 1) NLRP3 inflammasome; 2) gut microbiota; and 3) metabolic pathways; and how inflammasome signaling may affect depressive‐like behavior and gut microbiota composition. The implication is that novel therapeutic strategies could emerge for MDD and co‐morbid conditions. A number of testable predictions surface from this microbiota‐gut‐inflammasome‐brain hypothesis of MDD, using approaches that modulate gut microbiota composition via inflammasome modulation, fecal microbiota transplantation, psychobiotics supplementation, or dietary change. (shrink)

The amygdala is a key brain area regulating responses to stress and emotional stimuli, so improving our understanding of how it is regulated could offer novel strategies for treating disturbances in emotion regulation. As we review here, a growing body of evidence indicates that the gut microbiota may contribute to a range of amygdala-dependent brain functions from pain sensitivity to social behavior, emotion regulation, and therefore, psychiatric health. In addition, it appears that the microbiota is necessary for normal development of (...) the amygdala at both the structural and functional levels. While further investigations are needed to elucidate the exact mechanisms of microbiota-to-amygdala communication, ultimately, this work raises the intriguing possibility that the gut microbiota may become a viable treatment target in disorders associated with amygdala dysregulation, including visceral pain, post-traumatic stress disorder, and beyond. Also see the video abstract here: https://youtu.be/O5gvxVJjX18 The amygdala plays a central role in regulating many aspects of behavior in rodents and humans, from pain responding to social interaction and psychiatric function. Accumulating evidence suggests microbiota-to-amygdala communication along the gut-brain axis is a key modulator of these amygdala-dependent behaviors, with critical implications for health and disease. (shrink)