Milling, Simon and Ijaz, Umer Zeeshan and Venieri, Danae and Christidis, George E. and Rattray, Nicholas J. W. and Gounaki, Iosifina and Andrusaite, Anna and Hareendran, Aravind and Knapp, Charles W. and Jones, Alexander X. and Photos-Jones, Effie (2024) Beneficial modulation of the gut microbiome by leachates of Penicillium purpurogenum in the presence of clays: A model for the preparation and efficacy of historical Lemnian Earth. PLoS ONE, 19 (12): e0313090. ISSN 1932-6203

Abstract

The experiments presented here are based on the reconfiguration of an ancient medicine, Lemnian Earth (LE) (terra sigillata, stamped earth, sphragis), an acclaimed therapeutic clay with a 2500-year history of use. Based on our hypothesis that LE was not a natural material but an artificially modified one involving a clay-fungus interaction, we present results from experiments involving the co-culture of a common fungus, Penicillium purpurogenum (Pp), with two separate clay slurries, smectite and kaolin, which are the principal constituents of LE. Our results show: (a) the leachate of the Pp+smectite co-culture is antibacterial in vitro, inhibiting the growth of both Gram-positive and Gram-negative bacteria; (b) in vivo, supplementation of regular mouse diet with leachates of Pp+smectite increases intestinal microbial diversity; (c) Pp+kaolin does not produce similar results; (d) untargeted metabolomics and analysis of bacterial functional pathways indicates that the Pp+smectite-induced microbiome amplifies production of short-chain fatty acids (SCFAs) and amino acid biosynthesis, known to modulate intestinal and systemic inflammation. Our results suggest that the combination of increased microbial diversity and SCFA production indicates beneficial effects on the host microbiome, thus lending support to the argument that the therapeutic properties of LE may have been based on the potential for modulating the gut microbiome. Our experiments involving reconfigured LE open the door to future research into small molecule-based sources for promoting gut health.

People
Milling, Simon
Author

Milling, Simon and Ijaz, Umer Zeeshan and Venieri, Danae and Christidis, George E. and Rattray, Nicholas J. W. and Gounaki, Iosifina and Andrusaite, Anna and Hareendran, Aravind and Knapp, Charles W. and Jones, Alexander X. and Photos-Jones, Effie (2024) Beneficial modulation of the gut microbiome by leachates of Penicillium purpurogenum in the presence of clays: A model for the preparation and efficacy of historical Lemnian Earth. PLoS ONE, 19 (12): e0313090. ISSN 1932-6203

MacDonald, Lucy and Elmesmari, Aziza and Somma, Domenico and Frew, Jack and Di Mario, Clara and Madhu, Roopa and Paoletti, Audrey and Simakou, Theodoros and Hardy, Olympia M. and Tolusso, Barbara and Campobasso, Denise and Perniola, Simone and Gessi, Marco and Gigante, Maria Rita and Petricca, Luca and Bruno, Dario and Coletto, Lavinia Agra and Benvenuto, Roberta and Isaacs, John D. and Filby, Andrew and McDonald, David and Sim, Jasmine P.X. and Jamieson, Nigel and Wei, Kevin and D’Agostino, Maria Antonietta and Millar, Neal L. and Milling, Simon and McSharry, Charles and Gremese, Elisa and Affleck, Karen and Baker, Kenneth F. and McInnes, Iain B. and Otto, Thomas D. and Korsunsky, Ilya and Alivernini, Stefano and Kurowska-Stolarska, Mariola (2024) Synovial tissue myeloid dendritic cell subsets exhibit distinct tissue-niche localization and function in health and rheumatoid arthritis. Immunity, 57 (12). 2843-2862.e12. ISSN 1074-7613

Nichols, Ben and Briola, Anny and Logan, Michael and Havlik, Jaroslav and Mascellani, Anna and Gkikas, Konstantinos and Milling, Simon and Ijaz, Umer Zeeshan and Quince, Christopher and Svolos, Vaios and Russell, Richard K. and Hansen, Richard and Gerasimidis, Konstantinos (2024) Gut metabolome and microbiota signatures predict response to treatment with exclusive enteral nutrition in a prospective study in children with active Crohn’s disease. American Journal of Clinical Nutrition, 119 (4). pp. 885-895. ISSN 0002-9165

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Ijaz, Umer
Author

Cholet, Fabien and Vignola, Marta and Quinn, Dominic and Ijaz, Umer Z. and Sloan, William T. and Smith, Cindy J. (2025) Microbial ecology of drinking water biofiltration based on 16S rRNA sequencing: a meta-analysis. Water Research, 281: 123684. ISSN 0043-1354

Saleem, Farrukh and Ameer, Aqsa and Afzal, Farhan and Usman, Muhammad and Irshad, Hamid and Sattar, Sadia and Ijaz, Umer Zeeshan and Javed, Sundus (2025) A cross-sectional survey of poultry management systems, practices and antimicrobial use in relation to disease outbreak in Pakistan. BMC Research Notes, 18: 144. ISSN 1756-0500

Badar, Ayesha and Aqueel, Rhea and Nawaz, Ali and Ijaz, Umer Zeeshan and Malik, Kauser Abdulla (2025) Microbiota transplantation for Cotton Leaf Curl Disease suppression - core microbiome and transcriptome dynamics. Communications Biology, 8 (1): 380. ISSN 2399-3642

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Venieri, Danae
Author

Milling, Simon and Ijaz, Umer Zeeshan and Venieri, Danae and Christidis, George E. and Rattray, Nicholas J. W. and Gounaki, Iosifina and Andrusaite, Anna and Hareendran, Aravind and Knapp, Charles W. and Jones, Alexander X. and Photos-Jones, Effie (2024) Beneficial modulation of the gut microbiome by leachates of Penicillium purpurogenum in the presence of clays: A model for the preparation and efficacy of historical Lemnian Earth. PLoS ONE, 19 (12): e0313090. ISSN 1932-6203

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Christidis, George E.
Author

Milling, Simon and Ijaz, Umer Zeeshan and Venieri, Danae and Christidis, George E. and Rattray, Nicholas J. W. and Gounaki, Iosifina and Andrusaite, Anna and Hareendran, Aravind and Knapp, Charles W. and Jones, Alexander X. and Photos-Jones, Effie (2024) Beneficial modulation of the gut microbiome by leachates of Penicillium purpurogenum in the presence of clays: A model for the preparation and efficacy of historical Lemnian Earth. PLoS ONE, 19 (12): e0313090. ISSN 1932-6203

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Rattray, Nicholas J. W.
Author

Milling, Simon and Ijaz, Umer Zeeshan and Venieri, Danae and Christidis, George E. and Rattray, Nicholas J. W. and Gounaki, Iosifina and Andrusaite, Anna and Hareendran, Aravind and Knapp, Charles W. and Jones, Alexander X. and Photos-Jones, Effie (2024) Beneficial modulation of the gut microbiome by leachates of Penicillium purpurogenum in the presence of clays: A model for the preparation and efficacy of historical Lemnian Earth. PLoS ONE, 19 (12): e0313090. ISSN 1932-6203

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Gounaki, Iosifina
Author

Milling, Simon and Ijaz, Umer Zeeshan and Venieri, Danae and Christidis, George E. and Rattray, Nicholas J. W. and Gounaki, Iosifina and Andrusaite, Anna and Hareendran, Aravind and Knapp, Charles W. and Jones, Alexander X. and Photos-Jones, Effie (2024) Beneficial modulation of the gut microbiome by leachates of Penicillium purpurogenum in the presence of clays: A model for the preparation and efficacy of historical Lemnian Earth. PLoS ONE, 19 (12): e0313090. ISSN 1932-6203

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Andrusaite, Anna
Author

Milling, Simon and Ijaz, Umer Zeeshan and Venieri, Danae and Christidis, George E. and Rattray, Nicholas J. W. and Gounaki, Iosifina and Andrusaite, Anna and Hareendran, Aravind and Knapp, Charles W. and Jones, Alexander X. and Photos-Jones, Effie (2024) Beneficial modulation of the gut microbiome by leachates of Penicillium purpurogenum in the presence of clays: A model for the preparation and efficacy of historical Lemnian Earth. PLoS ONE, 19 (12): e0313090. ISSN 1932-6203

Nair, Reshmi and Lannagan, Tamsin R.M. and Jackstadt, Rene and Andrusaite, Anna and Cole, John and Boyne, Caitlin and Nibbs, Robert J.B. and Sansom, Owen J. and Milling, Simon (2024) Co-inhibition of TGF-β and PD-L1 pathways in a metastatic colorectal cancer mouse model triggers interferon responses, innate cells and T cells, alongside metabolic changes and tumor resistance. OncoImmunology, 13 (1): 2330194. ISSN 2162-4011

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Hareendran, Aravind
Author

Milling, Simon and Ijaz, Umer Zeeshan and Venieri, Danae and Christidis, George E. and Rattray, Nicholas J. W. and Gounaki, Iosifina and Andrusaite, Anna and Hareendran, Aravind and Knapp, Charles W. and Jones, Alexander X. and Photos-Jones, Effie (2024) Beneficial modulation of the gut microbiome by leachates of Penicillium purpurogenum in the presence of clays: A model for the preparation and efficacy of historical Lemnian Earth. PLoS ONE, 19 (12): e0313090. ISSN 1932-6203

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Knapp, Charles W.
Author

Milling, Simon and Ijaz, Umer Zeeshan and Venieri, Danae and Christidis, George E. and Rattray, Nicholas J. W. and Gounaki, Iosifina and Andrusaite, Anna and Hareendran, Aravind and Knapp, Charles W. and Jones, Alexander X. and Photos-Jones, Effie (2024) Beneficial modulation of the gut microbiome by leachates of Penicillium purpurogenum in the presence of clays: A model for the preparation and efficacy of historical Lemnian Earth. PLoS ONE, 19 (12): e0313090. ISSN 1932-6203

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Jones, Alexander X.
Author

Milling, Simon and Ijaz, Umer Zeeshan and Venieri, Danae and Christidis, George E. and Rattray, Nicholas J. W. and Gounaki, Iosifina and Andrusaite, Anna and Hareendran, Aravind and Knapp, Charles W. and Jones, Alexander X. and Photos-Jones, Effie (2024) Beneficial modulation of the gut microbiome by leachates of Penicillium purpurogenum in the presence of clays: A model for the preparation and efficacy of historical Lemnian Earth. PLoS ONE, 19 (12): e0313090. ISSN 1932-6203

See full publications list
Photos-Jones, Effie
Author

Milling, Simon and Ijaz, Umer Zeeshan and Venieri, Danae and Christidis, George E. and Rattray, Nicholas J. W. and Gounaki, Iosifina and Andrusaite, Anna and Hareendran, Aravind and Knapp, Charles W. and Jones, Alexander X. and Photos-Jones, Effie (2024) Beneficial modulation of the gut microbiome by leachates of Penicillium purpurogenum in the presence of clays: A model for the preparation and efficacy of historical Lemnian Earth. PLoS ONE, 19 (12): e0313090. ISSN 1932-6203

See full publications list
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