Dr Alexandre Almeida

Exploring the uncultured microbiome in health and disease

The study of the human gut microbiome has emerged as a new frontier of biomedical research. With the advent of high-throughput DNA sequencing, a strong link between the human gut microbiome composition and various aspects of human health is being increasingly recognized. However, thousands of bacterial species and viruses in the human gut microbiome are largely unknown, as they remain difficult to culture and experimentally characterize in vitro. This technical limitation represents a major hurdle to understanding the biological mechanisms and beneficial role of the gut microbiome in host health.

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Phylogenetic tree of bacteria in the human gut microbiome

Funded by an MRC Career Development Award, my research group combines computational and experimental approaches to understand the biological role of hidden gut-associated microbial diversity across multiple kingdoms (including bacteria, viruses and archaea), and to explore their antimicrobial potential.

Our main focus areas are:

Applying large-scale (meta)genomics techniques to investigate health-associated features and host-adaptive traits of the uncultured microbiome.
Develop targeted methods to cultivate novel members of the gut microbiome and enable further mechanistic investigations.
Combine in silico predictions with experimental validation to discover new gut-derived compounds with antimicrobial activity.

By providing an integrated view of the physiology and functions of the commensal microbiome, we seek to improve our understanding of their role in human health and open new avenues to develop innovative therapeutic applications.

If you are interested in pursuing a PhD or Postdoctoral position in my group feel free to get in touch with a CV and cover letter/statement explaining your interest in our research, so we can discuss future opportunities. Additional info on the application process for the PhD in Biological Sciences at the University of Cambridge can be found here.

Biography

Throughout my research career I have specialized in the development and application of bioinformatics and genomic approaches to make biological discoveries with relevance to human health. I obtained my PhD in Microbiology at the Institut Pasteur in Paris, where I studied the opportunistic pathogen group B Streptococcus to identify genomic traits linked to host adaptation (Almeida et al. Environ. Microbiol. 2016), virulence and pathogenicity (Almeida et al. J. Bacteriol. 2015 and Almeida et al. mSystems 2017). Using comparative genomics methods, we were able to identify candidate genes and single nucleotide variants linked with disease onset and progression (Almeida et al. mSystems 2017).

After my PhD, I was awarded an EBI-Sanger Postdoctoral (ESPOD) Fellowship and relocated to Cambridge to expand my research to metagenomic studies of the human gut microbiome. Using large-scale computational methods, we discovered thousands of uncultivated bacterial species in the human gut microbiome, more than tripling the number of gut-associated species previously known (Almeida et al. Nature 2019 and Almeida et al. Nat. Biotechnol. 2021). I have also been involved in a number of national and international collaborative projects, one of which led to the discovery of over 140,000 distinct viruses in the human gut microbiome, of which 50% were unknown before (Camarillo-Guerrero et al. Cell 2021).

Now, I have established a new research team at the Department of Veterinary Medicine in Cambridge, funded by an MRC Career Development Award, to understand the role that the hidden, uncultured microbiome plays in human health and disease.

Publications

Key publications:

See Google Scholar for full list of publications.

Almeida A, Mitchell AL, Boland M, Forster SC, Gloor GB, Tarkowska A, Lawley TD, Finn RD. A new genomic blueprint of the human gut microbiota. Nature 568(7753): 499-504 (2019).

Almeida A, Nayfach S, Boland M, Strozzi F, Beracochea M, Shi ZJ, Pollard KS, Sakharova E, Parks DH, Hugenholtz P, Segata N, Kyrpides NC, Finn RD. A unified catalog of 204,938 reference genomes from the human gut microbiome. Nature Biotechnology 39: 105–114 (2021).

Almeida A, Rosinski-Chupin I, Plainvert C, Douarre P-E, Borrego MJ, Poyart C, Glaser P. Parallel evolution of group B Streptococcus hypervirulent clonal complex 17 unveils new pathoadaptive mutations. mSystems 2(5): e00074-17 (2017).

Kashaf SS, Almeida A, Segre JA, Finn RD. Recovering prokaryotic genomes from host-associated, short-read shotgun metagenomic sequencing data. Nature Protocols 16: 2520–2541 (2021).

Kashaf SS, Proctor DM, Deming C, Saary P, Hölzer M, Taylor ME, Kong HH, Segre JA*, Almeida A*, Finn RD*. Integrating cultivation and metagenomics for a multi-kingdom view of skin microbiome diversity and functions. Nature Microbiology 7: 169-179 (2022). *Co-senior authors

Almeida A, Alves-Barroco C, Sauvage E, Bexiga R, Albuquerque P, Tavares F, Santos-Sanches I, Glaser P. Persistence of a dominant bovine lineage of group B Streptococcus reveals genomic signatures of host adaptation. Environmental Microbiology 18(11): 4216-4229 (2016).

Forster SC, Kumar N, Anonye BO, Almeida A, Viciani E, Stares MD, Dunn M, Mkandawire TT, Zhu A, Shao Y, Pike LJ, Louie T, Browne HP, Mitchell AL, Neville BA, Finn RD, Lawley TD. A human gut bacterial genome and culture collection for improved metagenomic analyses. Nature Biotechnology 37(2): 186–192 (2019).

Browne HP, Almeida A, Kumar K, Vervier K, Adoum AT, Viciani E, Dawson NJR, Forster SC, Cormie C, Goulding D, Lawley TD. Host adaptation in gut Firmicutes is associated with sporulation loss and altered transmission cycle. Genome Biology 22: 204 (2021).

Camarillo-Guerrero LF, Almeida A, Rangel-Pineros G, Finn RD, Lawley TD. Massive expansion of human gut bacteriophage diversity. Cell 184(4): 1098–1109.e9 (2021).

Beresford-Jones BS, Forster SC, Stares MD, Notley G, Viciani E, Browne HP, Kumar N, Vervier K, Almeida A, Lawley TD, Pedicord VA. The Mouse Gastrointestinal Bacteria Catalogue enables translation between the mouse and human gut microbiotas via functional mapping. Cell Host & Microbe 30: 124-138.e8 (2022).