Advances in sequencing technology have greatly expanded our ability to identify and survey the staggeringly diverse and ever-expanding microbial world1. Newly discovered species could be an untapped source of novel bioactive molecules such as antibiotics2; however, the potential of this vast microbial diversity has not been fully realized. Fewer than 2% of all microbial species are currently culturable3. This is due to a lack of knowledge about growth requirements3,4, and the tedious, labour-intensive experiments that stand in the way of this essential knowledge.
Privacy is a concern in human microbiome research. Identifying an individual using microbial DNA present in a sample that they provide is predicated on the relative stability of any given microbiome, its uniqueness to an individual, and the nature of the residual microorganisms that we leave in the environment. A growing body of evidence suggests that these three features of microbiomes could be exploited for forensic applications1,2,3. However, any human sample collected for microbiome analysis contains more than just microorganisms, because we shed human cells constantly, and human DNA sequences are often present in microbiome datasets. To allay privacy concerns in the National Institutes of Health’s Human Microbiome Project, removal methods for human DNA reads were pioneered4. These methods use computational screening of sequences against a human reference genome to identify and remove them. Although such methods are in use today, we need a comprehensive database to capture the unique variation that exists among human populations to be certain that all human DNA sequences have been removed. Such a database does not exist. Now writing in Nature Microbiology, Okada and colleagues5 report that there is substantial potential for identification of participants using metagenomes sequenced from human faecal samples.
Malnutrition and starvation are hallmark features of this eating disorder. The starvation state of AN includes gastrointestinal complaints such as excessive bloating, delayed gastric emptying, nausea, stomach pain and gastroparesis4. These symptoms present enormous obstacles to refeeding of patients, who often need to consume more than 4,000 kilocalories per day (usually over the course of months) during treatment to restore a healthy metabolic state. The presence of substantial gut dysbiosis could help to explain both the inefficiency of refeeding, as well as greater levels of distress that result from the high energy density and volume of refeeding regimens.
Urinary tract infections (UTIs), caused by bacteria such as uropathogenic E. coli (UPEC), are common in women and children. Approximately 25% of women with uncomplicated UTI suffer at least one follow-up infection within 6 months. These recurrent UTIs (rUTIs) are of particular concern as they are associated with adverse implications for patient quality of life and can lead to more severe and potentially fatal infections including sepsis. Multidrug resistance among infecting bacteria can also worsen the situation, as it leaves patients without treatment options. Targeting the pathways involved in recurrence has the potential to provide much-needed alternatives to address this major health problem.
Mycobacterium abscessus is an opportunistic pathogen that causes severe lung infections, particularly in patients with underlying lung disorders such as cystic fibrosis or chronic obstructive pulmonary disease1. The high pH in the airway lumen environment serves as a natural barrier, inhibiting the growth of many inhaled pathogens2, yet M. abscessus primarily colonizes this environment3. Although there are many cellular and animal models of M. abscessus pathogenesis4, they do not accurately simulate the pulmonary airway conditions where this bacterium causes infections, and it remains unclear how M. abscessus is able to survive such conditions. Now writing in Nature Microbiology, Sullivan and colleagues5 have developed a realistic air–liquid interface culture system for M. abscessus infection that they use to unveil the metabolic adaptations that enable this mycobacterium to withstand alkaline airway conditions, parlaying these results into potential therapeutic targets.
Bacterial communities are under continual selective pressure from bacteriophages (‘phages’), which typically outnumber prokaryotes by severalfold1. To counter this pressure, bacteria have evolved a diversity of phage resistance mechanisms. These include CRISPR-Cas systems that provide adaptive immunity and abortive infection systems in which an infected cell sacrifices itself to prevent phage proliferation2. When defence mechanisms are absent or fail to protect against phage pressure, subpopulations of phage-resistant bacterial mutants can emerge, most frequently with mutations causing the loss of phage receptors on the cell’s surface. Although resistant subpopulations can outcompete susceptible wild-type cells in the short term, mutations conferring phage resistance often come with a fitness cost3. For example, in Gram-positive bacteria, mutations conferring phage resistance can impact the composition of teichoic acids, which are common phage receptors and are also involved in essential cell processes such as attachment to surfaces, resistance to antimicrobials and virulence4. Phage-resistant mutants are often locked into their new states, as the likelihood that a subsequent mutation will restore altered or lost functions is extremely rare. Although resistant subpopulations can evade phage predation, they are less likely to thrive in the long term.
Adaptation of microbial populations to rapidly changing environmental conditions requires the transduction of a signal from the membrane to the cytoplasm, followed by a cascade of gene regulation to alter functionality1. It seems logical that clonal populations experiencing the same environmental cues and signals should respond in the same manner. For instance, in response to starvation, cells in a population of Bacillus subtilis will initiate sporulation2. In reality, however, such uniform cellular responses are not the norm.
Viral haemorrhagic fevers caused by pathogenic mammarenaviruses are endemic in certain regions of West Africa (Old World) and South America (New World). These emerging and primarily rodent-borne viruses can be transmitted from person-to-person via aerosols or direct contact with body secretions and present risks of epidemic or pandemic spread, as highlighted by repeated outbreaks of Lassa virus (LASV) infection in West African nations such as Nigeria, Guinea, Liberia and Sierra Leone1. In South America, the presence of haemorrhagic fever viruses has been known since the 1950s. There are currently several New World arenaviruses (NWAs) that can cause severe disease in this region, with mortality rates as high as 30%2. The most frequent causes of viral haemorrhagic fever in South America are the Junin (Argentina), Sabia (Brazil), Guanarito (Venezuela), Machupo (Bolivia) and Chapare (Bolivia) viruses. Each virus is harboured by its respective rodent host and is typically restricted to the host’s habitat range. Although infections and outbreaks have historically been sporadic, the high mortality associated with NWA infection, potential for human-to-human transmission and lack of effective available therapeutics underscores the need for an effective vaccine to target NWAs. Changes to the rodent host environment due to human activity and climate change also increase the potential of viral spillover and the emergence of viral haemorrhagic fever outbreaks.
Globally, 58 million people are chronically infected with hepatitis C virus (HCV)1, leading to fibrosis (that is, scarring of the liver), cirrhosis, liver failure and liver cancer. The gut and liver are connected through the hepatic portal vein, forming the gut–liver axis, but the relationship between gut processes and HCV infection outcome is poorly understood. In particular, interactions between the gut microbiome and the liver in HCV infection and fibrosis are an emergent area of research because perturbation of the gut–liver axis may have metabolic and immunologic consequences that persist after treatment. Now writing in Nature Microbiology, Ali and colleagues2 present a longitudinal multi-omics analysis designed to determine the impacts of gut microbiome processes and fibrosis on immunologic and metabolic outcomes in individuals with HCV. The study encompasses portal and peripheral blood, faeces and liver tissues, as well as the use of direct-acting antiviral (DAA) therapy to generate a sustained virologic response (SVR) or long-term evidence of viral eradication ≥12 weeks after DAA treatment.
