This week’s interesting studies that caught our attention in the field of microbiome research, microbial genomics and ecology, and others! Comments in blue are personal but hopefully useful to some!

Noteworthy studies and publications

(a) Microbiome

• Paternal microbiome perturbations impact offspring fitness.
  Ayele Argaw-Denboba et al. Nature — 1 May 2024.
  Comment: Quite an impressive find this week in Nature, in which authors report that altering the community of gut bacteria in male mice can have negative consequences for the health and lifespan of their offspring. Male mice given antibiotics targeting gut microbes showed RNA changes to their testes and sperm, which led to their offspring having a higher probability of growth issues. Authors even go to the extent of naming this a potential regulatory ‘gut–germline axis’ in males. It’s quite unclear whether this could be found in humans, but I suspect social and other external confounders would overwhelm that germline effect quite strongly. Still very interesting and puzzling. Well written “News & Views” associated article in Nature too.

• Oral bacteria relative abundance in faeces increases due to gut microbiota depletion and is linked with patient outcomes.
  Chen Liao et al. Nature Microbiology — 2 May 2024
  Comment: Interesting hypothesis-driven framing of this study. Authors investigate the increased relative abundance of oral bacteria in faeces in mice, and examine two competing interpretations: the ‘expansion’ hypothesis, where oral bacteria invade the gut ecosystem and expand, and the ‘marker’ hypothesis, where oral bacteria transit through the gut and their relative increase marks the depletion of other gut bacteria. The latter seems to prevail, which is (I believe) very impactful for microbiome studies in general. A lot is still unknown on the role and function of bacteria that transit in the gut vs. those that are established residents, and these results contribute to understanding this better.

• Microbiome confounders and quantitative profiling challenge predicted microbial targets in colorectal cancer development.
  Raúl Y. Tito et al. Nature Medicine — 30 April 2024.
  Comment (Camila): Authors show that a well-documented association between Fusobacterium and colorectal cancer (CRC) potentially disappears when controlling for confounders such as intestinal inflammation (measured by fecal calprotectin) or when using quantitative microbiome analysis (16S + flow cytometry to measure the microbial load). Authors carefully state that the results do not mean that Fusobacterium is not linked to CRC, but they rather suggest that the reasons behind this association might be much less straightforward (or less directly causal?) than originally considered. It will be interesting to see the impact of this study, as the links between CRC and the microbiome are well studied. The study also presents an interesting strategy to identify potential confounders in microbiome studies.

• Social and environmental transmission spread different sets of gut microbes in wild mice.
  Aura Raulo et al. Nature Ecology & Evolution — 1 May 2024.
  Comment: One of these very cool stories that is perhaps not surprising in hindsight, but that somebody had to look up. We know that microbes transmit between individuals, and observe individuals within families or households with more of the same microbes, for instance. In this article combining wild radio-tagged wood mice (to infer their social interactions) and 16S rRNA gut microbiota profiling, authors show that different sets of gut microbes spread through different groups: social contacts tend to spread more anaerobes whereas shared environments (without close contact) spread more aerophilic taxa. Seems intuitive, but implications are very interesting and it’s a very cool study!

• The impact of antibiotics on the gut microbiota of children recovering from watery diarrhoea.
  Son-Nam H. Le et al. npj Antimicrobials and Resistance — 22 April 2024.
  Comment: Interesting new paper from the OUCRU team in Vietnam. The study investigates the impact of antibiotics on the gut microbiota of children recovering from watery diarrhoea from a longitudinal cohort of a recent randomised control probiotic trial in Vietnam. Interestingly, it shows that when antibiotics were administered (~40% of these kids were treated with ciprofloxacin/cephalosporins), recovery was slower, as alpha and beta diversity remained lower for longer, with a transient overabundance of Enterococcus and depletion of Bifidobacterium pseudocatenulatum.

• Breaking the Barrier: The Role of Gut Epithelial Permeability in the Pathogenesis of Hypertension.
  Matthew Snelson, Tim Vanuytsel, Francine Marques. Nutrition & Hypertension — 12 April 2024.
  Comment: New review on the topic of gut health and hypertension by collaborators at Monash University. This one interestingly summarises what is known about the observation that hypertension increases gut permeability, with subsequent microbiome/health impacts. There is a scarcity of human studies while this is starting to be well observed in humans.

• Assessing phage-host population dynamics by reintroducing virulent viruses to synthetic microbiomes.
  Jacob Wilde et al. Cell Host & Microbe — 22 April 2024.
  Comment: We all know there is a world of phages in the gut and other microbial envionments, but they are quite difficult to study in their entirety for various technical and biological reasons. This very interesting work starts from the observation that bacterial colonies isolated from faeces are heavily depleted in virulent phages, as they are not amplified on synthetic media. From there, authors reintroduce virulent phages into synthetic strain communities (up to 73 strains) to show which ones can impact which susceptible microbes and their prophages.

• Unveiling microbial diversity: harnessing long-read sequencing technology.
  Agustinho et al. Nature Methods — 30 April 2024.
  Comment: Long-read sequencing applied to metagenomics is a very promising alternative but has been lagging due to scale-up costs and lack of specific tools. This is changing and this review is a good overview on this.

• Microbiota metabolism of intestinal amino acids impacts host nutrient homeostasis and physiology.
  Ting-Ting Li et al. Cell Host & Microbe — 23 April 2024.
  Comment: In the brain, serotonin acts as a neurotransmitter, but most serotonin is produced by the gut microbiota, and helps control bowel function and nutrient absorption. In this study, authors look at how the gut microbiota can deplete amino acids and affect AA homeostasis. They find that depletion of branched-chain AA and tryptophan regulates glucose tolerance via peripheral serotonin production, which has quite interesting implications linking diet and nutrient absorption.

• Transplantation of gut microbiota derived from patients with schizophrenia induces schizophrenia-like behaviors and dysregulated brain transcript response in mice.
  Nana Wei et al. Schizophrenia — 8 April 2024.
  Comment: Functional causal studies on the gut-brain axis are complicated to realise, low-powered and sometimes quite difficult to interpret. This is an interesting attempt in which authors transplanted the gut microbiota from schizophrenic patients into mice, and observed schizophrenia-like symptoms in social behaviour, as well as modifications in the brain transcriptomes.

• Deciphering the different phases of preclinical inflammatory bowel disease.
  Jonas Rudbaek et al. Nature Reviews Gastroenterology & Hepatology — 10 November 2023.
  Comment: I had missed this review on characterizing the various different stages of IBD, which is a very difficult spectrum to carefully diagnose and understand. Defining better diagnostics points will allow a better understanding of its progression. This review is very exhaustive on the matter, if you’re interested.

(b) Microbial genetics, ecology, evolution and AMR

• Akkermansia muciniphila exoglycosidases target extended blood group antigens to generate ABO-universal blood.
  Mathias Jensen et al. Nature Microbiology — 29 April 2024.
  Comment: Using microbes to engineer universal blood type has been a story in the making for a few years now. This led to the identification of carbohydrate-active enzymes able to convert of A and B blood group erythrocytes to blood group O (which was of prime importance for our interpretation of ABO-microbiota links in our 2022 microbiome GWAS work in which we found more of these CAZymes in taxa associated with ABO variation in humans). This study pushes the boundaries further, with the identification of exoglycosidases from the well-described mucin-degrading Akkermansia muciniphila. This strongly suggests that mucin-degrading bacteria could be valuable sources of enzymes for production of universal blood for transfusions. Exciting prospect!

• Ecological relevance of flagellar motility in soil bacterial communities.
  Josep Ramoneda et al. The ISME Journal — 22 April 2024.
  Comment: I really enjoyed reading this one. Bacteria (unsurprisingly) move towards food! Authors screened ~26,000 bacterial genomes across 12 phyla for flagellar genes as a proxy to predict flagellar motility. They observed that predicted motility seemed to be associated with a higher prevalence of genes for carbohydrate metabolism and higher maximum potential growth rates. Then, in 4 independent soil experiments collecting the microbiome and measuring gradients in soil carbon availability, they observed a positive relationship between flagellar motility and soil carbon availability in all datasets, validated by an in vitro soil incubation experiment.

• The three-species problem: Incorporating competitive asymmetry and intransitivity in modern coexistence theory.
  Ravi Ranjan et al. Ecology Letters — 11 April 2024.
  Comment: As more and more longitudinal microbiome samples are being generated, it becomes possible to model how species interact with each other. From a simplistic point of view, looking at variations in levels of co-abundant taxa (or how that co-abundance metric varies in time) can help us infer what are the growth/depletion dynamics of said taxa, and potentially how they interact ecologically. Until now, the best approaches for this were summarized well by models based on Lotka–Volterra equations, which were initially developed to model predator-prey competition interactions. In this paper, which I am not skilled enough to understand in precise detail, authors develop a way to introduce a third species into what has been traditionally a two-species model. Potentially very cool if applied to longitudinal microbiome datasets, I think!

• Fine-tuning the gut ecosystem: the current landscape and outlook of artificial microbiome therapeutics.
  Serena Porcari, William Fusco et al. The Lancet Gastroenterology — May 2024.
  Comment: This review focuses on very promising new applications of microbial bioengineering with health outcomes. Examples include the delivery of engineered Lactococcus lactis to deliver proinsulin and IL-10, to promote immune tolerance to proinsulin and suppress autoimmunity in type 1 diabetes patients. Another example is the delivery of cancer antigens as live attenuated vaccines for cervical, prostate, or pancreatic cancer via engineered Listeria monocytogenes. Finally some mention of engineered E. coli strains to degrade phenylalanine that detrimentally accumulates in patients with phenylketonuria.

(c) Other general interest

• A painless way to customize Circos plot: From data preparation to visualization using TBtools.
  Chengjie Chen et al. iMeta — 4 July 2022.
  Comment: An old publication that I had missed, and haven’t tried yet. From having done Circos plots in the past the hard way, this could help make them a bit more easily. Let us know if anyone has tried!

• CoCas9 is a compact nuclease from the human microbiome for efficient and precise genome editing.
  Eleonora Pedrazzoli et al. (Segata/Ceresto groups) Nature Communications — 24 April 2024.
  Comment: The CRISPR-Cas9 revolutionary genome editing tools that are based on microbial enzymes. In this study, authors screen a repository of MAGs from microbiomes and uncover a large variety of new Cas9 enzymes (n=17,173). They highlight a particular one, CoCas9, from Collinsella sp. which is highly active and high-fidelity, and can expand the current toolbox for genome editing.

• Genomic factors shape carbon and nitrogen metabolic niche breadth across Saccharomycotina yeasts.
  Dana A. Opulente et al. Science — 26 April 2024.
  Comment: A great effort in yeast genomics and ecology this week in Science. Based on sequences, metabolic diversity and phenotypes of 1,154 new yeasts, authors suggest a surprising lack of trade-off in growth rate between specialists and generalists. In other words, on particular substrates, specialists of that substrate don’t always seem to grow faster than generalists, which sometimes outcompete them. Puzzling and interesting!

Noteworthy preprints:

• Commensal bacteria inhibit viral infections via a tryptophan metabolite.
  Danting Jiang et al. bioRxiv — 21 April 2024.
  Comment: Authors found here that Lactobacillus gasseri and the Lachnospiraceae family are associated with enhanced resistance to SHIV infection in a pediatric nonhuman primate cohort. Two Lachnospiraceae in particular, Clostridium immunis and Ruminococcus gnavus, inhibited HIV replication in vitro and ex vivo via tryptophan metabolism into 3-indolelactic acid, which agonizes the aryl hydrocarbon receptor (AhR). Metagenomic analysis of individuals at risk for HIV showed a lower fecal abundance of the bacterial ArAT gene in those who acquired HIV compared to those who did not, indicating a protective role of ArAT-expressing bacteria in humans.

• A pervasive large conjugative plasmid mediates multispecies biofilm formation in the intestinal microbiota increasing resilience to perturbations.
  Leonor García-Bayona et al. bioRxiv — 29 April 2024.
  Comment: In this work, authors identify and characterize pMMCAT, a large conjugative plasmid, frequently transferred among Bacteroidales species and ubiquitous in diverse human populations (as profiled in 4,467 human faecal metagenomes from healthy adults in 26 countries). pMMCAT encodes both an extracellular polysaccharide and fimbriae and promotes multispecies biofilm formation in vitro and in the mammalian gut, which could explain its persistance and distribution.

• Long-term fasting remodels gut microbial metabolism and host metabolism.
  QR Ducarmon et al. bioRxiv — 19 April 2024.
  Comment: Very interesting and this is likely going to be an impactful paper! Fasting causes extensive remodelling of the gut microbiome at species level, affecting ~2/3 of examined species in this study. CAZyme profiling alone can reveal that a metabolic switch occurs during long-term fasting, from dietary fibers to host glycans, which does not seem to involve the main suspected species Akkermansia muciniphila. When looking at the serum metabolomes, they saw changes in ~52% metabolites after fasting, including microbiome-derived metabolites such as indole-3-propionic acid, suspected here to be produced by Oscillibacter with potential links to cardiometabolic health. Other results can be seen in this exhaustive paper, and on Robin Mesnage’s (senior author) tweet thread.

Other noteworthy things:

• New GTDB version released! This is release 09-RS220, including 596,859 genomes (48% increase from R08-RS214) and 113,104 species clusters (33% increase). Live at http://gtdb.ecogenomic.org. Release notes here. Release statistics here.
• If you need to build a $400 DIY plate imager, Ben Braverman (Arcadia Science) has a nice tweet thread about it here.