NLRP12 attenuates colon inflammation by maintaining colonic microbial diversity and promoting protective commensal bacterial growth

Inflammatory bowel diseases involve the dynamic interplay of host genetics, microbiome and inflammatory response. Here, we report that NLRP12, a negative regulator of innate immunity, is reduced in human ulcerative colitis by comparing monozygotic twins and other patient cohorts. In parallel, Nlrp12-deficiency in mice caused increased colonic basal inflammation, leading to a less-diverse microbiome, loss of protective gut commensal strains (Lachnospiraceae) and increased colitogenic strains (Erysipelotrichaceae). Dysbiosis and colitis susceptibility associated with Nlrp12-deficency were reversed equally by treatment with antibodies targeting inflammatory cytokines or by administration of beneficial commensal Lachnospiraceae isolates. Fecal transplants from specific pathogen free reared mice into germ-free Nlrp12-deficient mice showed that NLRP12 and the microbiome each contribute to immune signaling that culminates in colon inflammation. These findings reveal a feed-forward loop where NLRP12 promotes specific commensals that can reverse gut inflammation, while cytokine blockade during NLRP12-deficiency can reverse dysbiosis

Teamwork Makes the String Work: A Pilot Test of the Loose String Task with African Crested Porcupines (<i>Hystrix cristata</i>)

Comparative researchers have heavily focused their studies of social cognition on species that live in large social groups, while neglecting other potential predictors of social cognition. African crested porcupines (Hystrix cristata) are relatively rare among mammals in that they are cooperative breeders that pair for life. Little is known about their social cognition, but they are good candidates for exploring cooperative behavior due to the need to coordinate behavior to cooperatively raise young. Cooperation, as defined in this study, is the process by which two or more participants perform independent actions on an object to obtain a reward for all parties. Humans are thought to outperform all other species in the frequency and magnitude of cooperative behaviors. Yet, only by studying a variety of species can researchers fully understand the likely selection pressures for cooperation, such as cooperative breeding. Here, we pilot tested the feasibility of the popular loose-string task with a mated pair of African crested porcupines, a task that required the porcupines to cooperatively pull ropes to access an out of reach platform baited with food rewards. Other species presented with this task were able to work together to receive rewards but did not always demonstrate understanding of the role of their partner. The porcupines achieved success but did not appear to coordinate their actions or solicit behavior from their partner. Thus, similar to other species, they may achieve success in this task without taking their partner’s role into account. This study demonstrates that the loose string task can be used to assess cooperation in porcupines. However, further experiments are needed to assess the porcupine’s understanding of their partner’s role under this paradigm