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SummaryReversible genomic DNA-inversions control expression of numerous bacterial molecules in the human gut, but how this relates to disease remains uncertain. By analyzing metagenomic samples from six human Inflammatory Bowel Disease (IBD) cohorts combined with mice experimentation, we identified multiple invertible regions in which a particular orientation was correlated with disease. These include the promoter of the anti-inflammatory polysaccharide-A (PSA) ofBacteroides fragilis, which is mostly oriented ‘OFF’ during inflammation but switches to the ‘ON’ orientation when inflammation is resolved. We further detected increased abundances ofB. fragilisassociated bacteriophages in patients with the PSA ‘OFF’ orientation. Isolation and analysis of aB. fragilisassociated bacteriophage revealed that it induced the PSA ‘OFF’ switch, thereby altering the bacterial induced immune modulation. Altogether, we reveal large-scale dynamic and reversible bacterial phase variations driven both by bacteriophages and the host inflammatory state signifying bacterial functional plasticity and suggesting potential clinical interventions.

Many countries are currently in a state of lockdown due to the SARS-CoV-2 pandemic. One key requirement to safely transition out of lockdown is the continuous testing of the population to identify infected subjects. Currently, detection is performed at points of care using quantitative reverse-transcription PCR, thus requiring dedicated professionals and equipment. Here, we developed a protocol based on reverse transcribed loop-mediated isothermal amplification for the detection of SARS-CoV-2. This protocol is applied directly to SARS-CoV-2 nose and throat swabs, with no RNA purification step required. We tested this protocol on over 180 suspected patients, and compared the results to those obtained using the standard method. We further succeeded in applying the protocol to self-collected saliva samples from confirmed cases. Since the proposed protocol can detect SARS-CoV-2 from saliva and provides on-the-spot results, it allows simple and continuous surveillance of the community. Impact statement Humanity is currently experiencing a global pandemic with devastating implications on human health and the economy. Most countries are gradually exiting their lockdown state. We are currently lacking rapid and simple viral detections, especially methods that can be performed in the household. Here, we applied RT-LAMP directly on human clinical swabs and self-collected saliva samples. We adjusted the method to allow simple and rapid viral detection, with no RNA purification steps. By testing our method on over 180 human samples, we determined its sensitivity, and by applying it to other viruses, we determined its specificity. We believe this method has a promising potential to be applied world-wide as a simple and cheap surveillance test for SARS-CoV-2.

Gut bacteria were shown to exert pivotal effects on health and disease. However, mechanistic studies of gut bacterial communities are limited due to the lack of technologies for real-time studies on live bacteria. Here, we developed COMBInatorial cliCK-chemistry (COMBICK) labeling on human gut-derived bacteria, both aerobic and anaerobic strains, to enable dynamic tracing of live, heterogeneous bacterial communities on the strain level, including clinical isolates of the Enterobacteriaceae family. We further show that COMBICK labeling is applicable on anaerobic bacterial strains directly isolated from stool. In COMBICK, the number of labeled bacteria that can be simultaneously differentiated increases exponentially depending on the availability of fluorophores and machine capabilities. This method allows real-time studies of bacterial communities from a variety of ecosystems, and can significantly advance mechanistic research in the microbiome field.

The gut microbiota and the immune system have co-evolved to interact and cooperate in many ways. A recent study characterizing the immunomodulatory effects of over 60 different human-derived gut microbes across phyla showed that bacteria-induced immunomodulations are not dictated by the bacterial phylogeny. Yet, it remains unclear whether strains from the same species induce the same immunomodulatory effects on the host. We analyzed the strain-level data from this recent study and found that strains from the same species can induce distinct and sometimes even opposing immunophenotypes. Hence, we suggest that the immunomodulatory capabilities of gut bacteria can be strain-specific.

Our emerging view of the gut microbiome largely focuses on bacteria, while less is known about other microbial components such as bacteriophages (phages). Though phages are abundant in the gut, very few phages have been isolated from this ecosystem. Here, we report the genomes of 27 phages from the United States and Bangladesh that infect the prevalent human gut bacterium Bacteroides thetaiotaomicron. These phages are mostly distinct from previously sequenced phages with the exception of two, which are crAss-like phages. We compare these isolates to existing human gut metagenomes, revealing similarities to previously inferred phages and additional unexplored phage diversity. Finally, we use host tropisms of these phages to identify alleles of phage structural genes associated with infectivity. This work provides a detailed view of the gut’s “viral dark matter” and a framework for future efforts to further integrate isolation- and sequencing-focused efforts to understand gut-resident phages.

Many countries are currently in a lockdown state due to the SARS-CoV-2 pandemic. One key aspect to transition safely out of lockdown is to continuously test the population for infected subjects. Currently, detection is performed at points of care using quantitative reverse-transcription PCR (RT-qPCR), and requires dedicated professionals and equipment. Here, we developed a protocol based on Reverse Transcribed Loop-Mediated Isothermal Amplification (RT-LAMP) for detection of SARS-CoV-2. This protocol is applied directly on SARS-CoV-2 nose and throat swabs, with no RNA purification step required. We tested this protocol on over 180 suspected patients, and compared its results to the standard method. We further succeeded to apply the protocol on self-sampled saliva from confirmed cases. Since the proposed protocol provides results on-the-spot, and can detect SARS-CoV-2 from saliva, it can allow simple and continuous surveillance of the community.

Increasing evidence indicates that the brain regulates peripheral immunity, yet whether and how the brain represents the state of the immune system remains unclear. Here, we show that the brain's insular cortex (InsCtx) stores immune-related information. Using activity-dependent cell labeling in mice (FosTRAP), we captured neuronal ensembles in the InsCtx that were active under two different inflammatory conditions (dextran sulfate sodium [DSS]-induced colitis and zymosan-induced peritonitis). Chemogenetic reactivation of these neuronal ensembles was sufficient to broadly retrieve the inflammatory state under which these neurons were captured. Thus, we show that the brain can store and retrieve specific immune responses, extending the classical concept of immunological memory to neuronal representations of inflammatory information.

SARS-CoV-2 has quickly spread all around the globe causing illness and wide damages. Most countries were unprepared for such a rapid spread and crisis. This led to various strategies for effective control of the new pandemic. A key aspect in all countries was to effectively test the population for the virus. Most countries chose a lockdown strategy in which many workplaces and activities are completely closed, leading to substantial economy costs. Here, we present a protocol we recently developed that allows rapid and simple detection of SARS-CoV-2 for the large population, eliminating costs and involvement of professional teams and laboratories. This protocol is based on Reverse Transcribed Loop-Mediated Isothermal Amplification (RT-LAMP). We tested this protocol directly on patient samples, both nasal and throat clinical swabs as well as saliva. Notably, this protocol is simple, cheap and can be easily applied to other pathogens as well.

Increasing evidence indicates that the brain regulates peripheral immunity. Yet, it remains unclear whether and how the brain represents the state of the immune system. Here, we show that immune-related information is stored in the brain’s insular cortex (InsCtx). Using activity-dependent cell labeling in mice (FosTRAP), we captured neuronal ensembles in the InsCtx that were active under two different inflammatory conditions (DSS-induced colitis and Zymosan-induced peritonitis). Chemogenetic reactivation of these neuronal ensembles was sufficient to broadly retrieve the inflammatory state under which these neurons were captured. Thus, we show that the brain can encode and initiate specific immune responses, extending the classical concept of immunological memory to neuronal representations of immunity.

The 'gut-brain axis' is a fairly new term in the fairly new field of the gut microbiota. The gut microbiota, the collection of microorganisms residing in intestines of vertebrates, was shown to have major effects on host physiology. The field has seen a renaissance due to advances in deep-sequencing. Recently, there is an explosion of studies on the physiological and therapeutic potential of the gut microbiota. These microbes are considered to reside in symbiosis with their hosts, and are termed 'commensals', originated from Latin - 'at table together'. We provide the gut microbes nutrients and a living niche, and they in turn, provide us with essentially the same - nutrients derived from the food we eat, that we cannot digest, and essential functions for health and longevity. In the past few years it has been appreciated that gut microbes can even affect our brain, behavior, and neurological disorders, which we here review.