Annual leave last week so two weeks will be grouped into one for this post! Here is a summary of what caught caught our eye recently in the field of microbiome research, microbial genomics and ecology, and others. Comments in blue are personal and hopefully useful. A reminder that you can subscribe to this weekly list via WordPress (bottom right of the screen) or the RSS feed. I also advertise these posts on Twitter, BlueSky and LinkedIn, but feel free to share them wherever. Hopefully this is interesting to some, let us know! 🙂

Noteworthy studies and publications

(a) Microbiome

• Spatially resolved lipidomics shows conditional transfer of lipids produced by Bacteroides thetaiotaomicron into the mouse gut
  Claudia Mirretta Barone et al. Cell Host & Microbe — 24 May 2024.
  Comment: Very interesting methodological study, using MALDI mass spectrometry method to colocalize host and bacterial lipids. In this study on mice, authors identify 103 lipids from Bacteroides thetaiotaomicron which were mapped across various regions of the colon. Among the interesting results, mice colonized with B. thetaiotaomicron lacking sphingolipids have increased bacterial lipid uptake, and microbial phosphatidic acid was identified as the greatest signal for host lipid transfer.

• Gut microbiome correlates of recurrent urinary tract infection: a longitudinal, multi-center study
  JooHee Choi, Robert Thänert et al. eClinicalMedicine — 26 April 2024.
  Comment: How are UTIs linked to gut microbiome composition? No groundbreaking new knowledge on the matter from this recent study but it is well executed and a good, clear read. In this multi-centre (USA) longitudinal (2016 to 2019) cohort study, 125 patients with UTI caused by an antibiotic-resistant bacteria were recruited and had matching samples collected (644 stool samples, 895 UPEC isolates for AMR gene characterisation and phenotyping). They find that the gut microbiome is implicated in recurrent UTI and serves as an AMR gene reservoir for UPEC, which can asymptomatically colonize the gut and the urinary tract. The recurrence of UTI involves post-antimicrobial blooms of gut E. coli among urinary tract-colonized patients, which unsurprisingly suggests that cross-habitat migration of UPEC is an important mechanism of recurrent UTI.

• Microbiome research in Africa must be based on equitable partnerships.
  Ovokeraye H. Oduaran et al. Nature Medicine — 23 May 2024.
  Comment: Medicine in general and microbiome science in particular are still very biased towards Western countries and their populations and there is a crucial need to include more human diversity in research data and studies, but it should be done with considerations of equity, empowerment and representativity. Authors present here an implementation framework for African microbiome research, which includes local research leadership, ethical and equitable partnerships but also standardized microbiome protocols and governmental involvement. I have been impressed by the quality of seminars from the H3Africa Microbiome Task Force in the past, so this is really a great addition now.

• Gut bacteria convert glucocorticoids into progestins in the presence of hydrogen gas
  Megan D. McCurry et al. Cell — 24 May 2024.
  Comment: It has been observed in the past that microbes are able to interact with host-produced steroids but the mechanisms are unclear. Here, authors show that gut microbes from the Gordonibacter and Eggerthella genera are able to convert corticoids from the bile into progestins, a form of the sex hormone progesterone, in an enzymatic step called 21-dehydroxylation that requires microbially-produced gaseous hydrogen. Progestin levels and the presence of gut microbial gene clusters involved in 21-dehydroxylation were found to be significantly more abundant during pregnancy, which suggests that gut microbes can importantly affect physiology and hormone balance during that phase of life.

• Linking microbiome temporal dynamics to host ecology in the wild
  Kirsty J. Marsh et al. Trends in Microbiology — 25 May 2024.
  Comment: Nice microbiome ecology opinion piece on the need for more individual longitudinal variation in microbiome science. Authors use example animal hosts to summarize what is known, possible mechanisms and associated methodology and challenges.

• Towards a Health-Associated Core Keystone (HACK) index for the human gut microbiome
  Abhishek Goel et al. bioRxiv — 27 May 2024.
  Comment: It is always interesting to have meaningful comparators between individual microbiomes, but oh my, how challenging can this be. What do you choose, how do you do it? Is it even possible to reduce the microbiota’s complexity to a single index score? an interesting way could be to look at the “core microbiome” (a tricky concept) and how much individuals vary from it. As debatable as this is, it’s interesting to see what people are trying when the answers are not clear sometimes. In this recent effort, authors suggest that their “HACK-index” can provide a more reliable framework for identifying and comparing gut microbiome markers of health across various demographics and disease states. Maybe worth looking at? And check out the thread from senior author Tarini Shankar Ghosh.

• The protective role of commensal gut microbes and their metabolites against bacterial pathogens
  Liqin Cheng et al. Gut Microbes — 26 May 2024.
  Comment: In this recent study, authors venture in the field of colonization resistance and exhaustively test the supernatants of 74 commensal gut microbial species cultured in vitro for their interaction with Salmonella, aiming for protective effects affecting pathogenic growth. It remains to be seen how these actually mean in complex real-life systems, but the analysis is nonetheless interesting to read.

• The impact of gestational diabetes on functional capacity of the infant gut microbiome is modest and transient
  Ryan V. Chieu et al. Gut Microbes — 26 May 2024.
  Comment: Gestational diabetes (GDM) is quite common in pregnant women, but its impact on the infant’s subsequent microbiota is not well known. This study compares pairs of mothers (16 of which who experienced maternal GDM and 14 without) and their infants 1 year after birth. Authors observe that the mode of delivery is the biggest contributor, irrespective of GDM, and that any possible mild effects from GDM are not persisting in infants after 12 months of life.

• Salmonella Typhimurium expansion in the inflamed murine gut is dependent on aspartate derived from ROS-mediated microbiota lysis
  Woongjae Yoo, Nicholas G. Shealy et al. Cell Host & Microbe — 27 May 2024.
  Comment: This paper adds to the considerable list of studies looking at how gastrointestinal pathogens like Salmonella invade and thrive in the inflamed (mouse) gut. It is quite ecologically interesting to understand how introduced, virulent microbes can hijack functional communities and their metabolic products for their benefit. Here, authors show that Salmonella can use aspartate from the gut microbiota for growth in mice with colitis, enabling anaerobic fumarate respiration in the pathogen and allowing it to expand in the gut. In turn, ROS produced by the host in response to inflammation has the effect to lyse gut commensals and increase aspartate availability to Salmonella. A tight tale of adaptation and co-evolution!

• A Gram-negative-selective antibiotic that spares the gut microbiome
  Kristen A. Muñoz et al. Nature — 29 May 2024.
  Comment: A lot of hype has already been made on this paper, including a descriptive commentary here. I am a bit on the fence, honestly. Briefly, in this study, authors find and engineer a molecule, called “lolamicin”, which specifically targets an essential system (encoded by 5 genes from the lol operon) responsible for lipoprotein transport between the inner and outer membranes in Gram-negative bacteria. Because of this, authors claim that the action of lolamicin spares Gram-positive bacteria and “non-pathogenic Gram-negative bacteria” (this is the bit I have some conceptual issue with, as pathogen vs. commensal is more than a hot debate when you consider things that broadly). Nonetheless, it is obviously a very interesting effort for when obvious Gram-negative pathogens are infecting, such as C. difficile (tested in the paper). Interesting to imagine how bacteria could evolve resistance to this.

• A strategy for differential abundance analysis of sparse microbiome data with group-wise structured zeros
  Fentaw Abegaz et al. Scientific Reports — 30 May 2024.
  Comment: Differential abundance methods are themselves quite abundant in the literature, and each are having their pros and cons (check out this very nice recent comparison from our collaborator Leo Lahti as well as this very well-explained benchmarking in the ZicoSeq paper). This recent manuscript presents a new DAA approach which claims to address the specificities of microbiome data better (including inflated zero counts, overdispersion, and non-normality). Perhaps worth considering, and interesting to see what people think.

• Binding of Akkermansia muciniphila to mucin is O-glycan specific
  Janneke Elzinga et al. Nature Communications — 29 May 2024.
  Comment: Somehow I find mucin-degrading bacteria fascinating. I know, this is a bit of a weird ice-breaker in parties, but such nice microbial biochemistry research is done to understand how the gut microbiome as a dynamic whole juggles between using dietary nutrients vs. mucin. In this new study, authors characterise even further the mucin-binding abilities of a big suspect in gut health (and mucin degradation, as its name suggests), Akkermansia muciniphila. They show that it is able to selectively recognize the unsialylated LacNAc on O-glycans from mucin.

(b) Microbial genetics, ecology, evolution and AMR

• Estimating the effect of antimicrobial resistance genes on minimum inhibitory concentration in Escherichia coli
  Samuel Lipworth et al. medRxiv — 17 May 2024.
  Comment: There is a large effort in trying to predict antimicrobial resistance phenotypes in bacterial pathogens from minimum inhibitory concentration (MIC) in vitro tests. There are arguments as to how relevant and realistically those MIC tests are performed, but in this preprint from Nicole Stoesser’s lab in Oxford, authors use a collection of ~2.9k phenotyped and sequenced E. coli to look at another problem: what happens to the MIC measurement when pathogens acquire new resistance genes? They find evidence of various effects, additive or not, and suggest a way to predict outcomes of AMR gene acquisition.

• Human gut-associated Bifidobacterium species salvage exogenous indole, a uremic toxin precursor, to synthesize indole-3-lactic acid via tryptophan
  Cheng Chung Yong et al. Gut Microbes — 5 May 2024.
  Comment: This study shows that human gut-associated Bifidobacterium can convert exogenous indole into tryptophan and then indole-3-lactic acid (ILA), an immunomodulatory compound, using tryptophan synthase β subunit (TrpB) and aromatic lactate dehydrogenase (ALDH). Exogenous indole is known to contribute to the progression of kidney dysfunction after absorption by the intestine and sulfation in the liver, so any potential way to reduce its concentrations in the gut could be an interesting candidate probiotic activity.

• Pipolins are bimodular platforms that maintain a reservoir of defense systems exchangeable with various bacterial genetic mobile elements
  Víctor Mateo-Cáceres & Modesto Redrejo-Rodríguez bioRxiv — 22 May 2024.
  Comment: Bacteria have evolved various systems to protect themselves against viral infections and other genetic mobile elements. In this preprint, authors present a new category of integrated defense system based on primer-independent DNA polymerase B, which they term “pipolins”. They find them to be common in Gammaproteobacteria, but also on plasmids in other taxa.

• Metabolism of l-arabinose converges with virulence regulation to promote enteric pathogen fitness
  Curtis Cottam et al. PNAS — 25 May 2024.
  Comment: Another interesting effort showing how pathogens adapt and co-evolve with their hosts when it comes to infecting them. This study identifies a novel ʟ-arabinose uptake system called Aau in EHEC and Citrobacter that enhances virulence and fitness by linking the arabinose metabolism to the regulation of a type 3 secretion system (T3SS), independently from its role as a nutrient source. It interestingly challenges the traditional view of nutrient sensing, by showing that the metabolism of ʟ-arabinose, rather than its mere presence, is a key regulator of virulence factor expression in EHEC.

• Foodborne bacterial pathogens: genome-based approaches for enduring and emerging threats in a complex and changing world
  Alison E. Mathers et al. Nature Reviews Microbiology — 24 May 2024.
  Comment: Interesting review on pathogen control in the food chain using genome-based approaches. An interesting part of this review focuses on external factors like climate change and consumer preferences and how they shape the ecology of foodborne pathogens.

• Acanthamoeba castellanii as a model for unveiling Campylobacter jejuni host-pathogen dynamics
  Fauzy Nasher et al. bioRxiv — 24 May 2024.
  Comment: It is fascinating to imagine that protist predation is actually one of the biggest (if not the main) selective pressure on bacteria in the wild. As such, some believe that host-association in general could have evolved from bacteria surviving predation by living inside protists. More practically, this means that some pathogens are able to do it, and it might confer them additional protection and transmission potential. In this preprint, authors describe the interaction between a zoonotic pathogen Campylobacter jejuni and the amoeba A. castellanii in various ways. Very interesting links with lactate production are suggested.

• How low can you go? Short-read polishing of Oxford Nanopore bacterial genome assemblies
  George Bouras et al. Microbial Genomics — 4 June 2024.
  Comment: New interesting one from our collaborator and friend Ryan Wick and colleague George Bouras (and others) nicely looking at assembly polishing, and how to produce highly accurate microbial genome assemblies. They present a new approach, named Pypolca (github here) and suggest best practice in combination with Ryan’s Polypolish tool (github here).

• Developing a selective culturing approach for Campylobacter hepaticus
  Sheaaz G. J. Sakur, Sarah L. Williamson et al. Plos One — 31 May 2024.
  Comment: My Campylobacter past is always haunting me (in a good way) (I hope). In this interesting brief paper, authors show how to selectively culture C. hepaticus, the aetiological agent of spotty liver disease in chicken. This will hopefully help boosting research on this pathogen that causes lots of animal mortality and welfare/economical concerns.

• Screening clinical Candida albicans isolates for invasiveness by mimicking the human environment
  Clément Vulin et al. bioRxiv — 27 May 2024.
  Comment: One of my failings is probably that I am generally less interested in the absolute latest fungal research, but this one caught my eye as authors sought to study Candida albicans, a clinical fungal pathogen, using an interesting set of in vitro conditions carefully picked to mimic the human environment. These included 48 environmental conditions, including combinations of glucose/nitrogen concentrations, pH and temperature. Such a panel would be great for lots of human microbiology research.

• The atmosphere: a transport medium or an active microbial ecosystem?
  Rachael Lappan et al. The ISME Journal — 28 May 2024.
  Comment: Microbes are present in the air. They are part of the water cycle, through aerosolisation from plant evaporation and subsequent precipitation. This is a very cool perspective from Rachael Lappan and Chris Greening (Monash University, Melbourne, Aus.) presenting arguments on whether the atmosphere is only there for microbial transport or could constitute an ecosystem of its own. This piece also comes after the Greening lab showed last year that some bacteria could perform “aerotrophy” and use atmospheric hydrogen as a source of energy, so this is a really cool topic.

(c) Other general interest

• Why not eliminate HTLV-1 while eliminating HIV-1?
  Goedele N Maertens et al. The Lancet — 25 May 2024.
  Comment: Human T-cell leukaemia virus 1 (HTLV-1)-1 is an oncovirus, the largest incidence of which is in Australia, particularly in indigenous populations (it also disproportionately affects First Nations elsewhere in the world). People living with HTLV-1 infection have a 57% increase in mortality rate, with 5–10% of them developing life-threatening diseases, such as aggressive blood cancer, adult T-cell leukaemia or lymphoma, and HTLV-1 associated myelopathy, a progressive, painful walking disability. There is a lot to do in public awareness of HTLV-1, as well as steps to ensure its eradication, as explained in this important opinion piece.

• Do grant proposal texts matter for funding decisions? A field experiment
  Müge Simsek et al. Scientometrics — 19 May 2024.
  Comment: Another grain of salt for a frustrating problem. Submitting and assessing grants is a frustrating process for both parties involved, and it has been suggested (and calculated) a while ago that the amount of salary-hours spent by publicly-funded researchers writing lengthy unsuccessful grants often outweighs the amount of public money awarded by governments. This is, at worst, a fundamental financial issue in how our governments fund research, and it really not helped when funding bodies ask for extremely unnecessarily lengthy proposals (looking at you ERC). In this paper, the Dutch Research Council (NWO) did a field experiment in which they asked a grant-reviewing panel to assess proposals. They randomly split the panel according to whether the applicant submitted (1) a CV and a one-paragraph summary of the proposed research or, (2) a CV and a full detailed proposal of many pages (taking considerably more time to prepare for researchers). They found that withholding proposal texts from reviewers did not detectibly impact their proposal rankings. This raises a lot of questions on how grant proposals are currently asked to be made. There probably isn’t an easy answer to this, but hopefully a much-needed change will come, soon.

Other things:

• A hybrid conference from the Wellcome Trust series on “Genome Informatics” (13-15 November 2024 in Hinxton, UK) is being advertised. Abstract submission deadline is 10th September 2024. Zamin Iqbal has more information on Twitter.

• A 10-year old Winogradsky column sitting in the office window of Joseph Vallino (University of Chicago’s Marine Biological Laboratory at Woods Hole, MA, USA) has started to develop a great black spot. The thrilling mystery is documented on Twitter.