̽��ֱ�� of Cambridge - Kiran Patil

MICROBIOME: the kingdom of the gut

jg533 — Thu, 24 Aug 2023 08:50:40 +0000

What's so special about the bacteria in our bowels?

Gut bacteria accumulate many common medications and may reduce their effectiveness

jg533 — Wed, 08 Sep 2021 15:00:00 +0000

These interactions - seen for many drugs including those used to treat depression, diabetes, and asthma - could help researchers to better understand how drug effectiveness and side-effects differ between individuals. ̽��ֱ��study is published today in the journal Nature.

It is known that bacteria can chemically modify some drugs, a process known as biotransformation. This study, led by researchers from the Medical Research Council (MRC) Toxicology Unit at the ̽��ֱ�� of Cambridge and the European Molecular Biology Laboratory (EMBL) in Germany, is the first to show that certain species of gut bacteria accumulate human drugs, altering the types of bacteria in the gut and their activity.

This could change the effectiveness of the drug both directly, as the accumulation could reduce the availability of the drug to the body, and indirectly, as altered bacterial function and composition could be linked to side-effects.

̽��ֱ��human gut naturally contains communities of hundreds of different species of bacteria, which are important in health and disease, called the gut microbiome. ̽��ֱ��composition of bacterial species varies significantly between people and has previously been shown to be associated with a wide range of conditions including obesity, immune response, and mental health.

In this study, the researchers grew 25 common gut bacteria and studied how they interacted with 15 drugs that are taken orally. ̽��ֱ��drugs were chosen to represent a range of different types of common drugs, including antidepressant medications, which are known to affect individuals dissimilarly and cause side effects such as gut problems and weight gain.

̽��ֱ��researchers tested how each of the 15 drugs interacted with the selected bacterial strains – a total of 375 bacteria-drug tests. They found 70 interactions between the bacteria and the drugs studied, of which 29 had not been previously reported.

While earlier research has shown bacteria can chemically modify drugs, when the scientists studied these interactions further they found that for 17 of the 29 new interactions the drug accumulated within the bacteria without being modified.

Dr Kiran Patil at the ̽��ֱ�� of Cambridge’s MRC Toxicology Unit, who co-led the study, said: “It was surprising that the majority of the new interactions we saw between bacteria and drugs were the drugs accumulating in the bacteria. Until now, biotransformation was thought to be the main way that bacteria affect the availability of drugs to the body.”

“These will likely be very personal differences between individuals, depending on the composition of their gut microbiota. We saw differences even between different strains of the same species of bacteria.”

Examples of drugs that accumulated in bacteria include antidepressant duloxetine and anti-diabetic rosiglitazone. For some drugs, such as montelukast (an asthma drug) and roflumilast (for chronic obstructive pulmonary disease), both changes happened in different bacteria - they were accumulated by some species of bacteria and modified by others.

̽��ֱ��researchers also found the bioaccumulation of drugs alters the metabolism of the accumulating bacteria. For example, the antidepressant drug duloxetine bound to several metabolic enzymes within the bacteria and altered their secreted metabolites.

̽��ֱ��researchers grew a small community of several bacterial species together and found the antidepressant duloxetine dramatically altered the balance of bacterial species. ̽��ֱ��drug altered the molecules produced by the drug-accumulating bacteria, which other bacteria feed on, so the consuming bacteria grew much more and unbalanced the community composition.

̽��ֱ��researchers tested the effects further using C. elegans, a nematode worm commonly used to study gut bacteria. They studied duloxetine, which had been shown to accumulate in certain bacteria but not others. In worms grown with the species of bacteria that had been shown to accumulate the drug, the behavior of the worms was altered after being exposed to duloxetine, compared with worms that were grown with bacteria that did not accumulate duloxetine.

Dr Athanasios Typas at EMBL, who co-led the study, said: “Only now are people recognising that drugs and our microbiome impact each other with a critical consequence to our health.”

Dr Peer Bork at EMBL, and a co-lead of the study, said: “This calls for us to start treating the microbiome as one of our organs.”

Dr Patil said: “ ̽��ֱ��next steps for us will be to take forward this basic molecular research and investigate how an individual’s gut bacteria tie with the differing individual responses to drugs such as antidepressants – differences in whether you respond, the drug dose needed, and side effects like weight gain. If we can characterise how people respond depending on the composition of their microbiome, then drug treatments could be individualised.”

̽��ֱ��researchers caution that the study findings are only on bacteria grown in the lab, and more research is needed to understand how bioaccumulation of medications by gut bacteria manifests inside the human body.

̽��ֱ��study started as a collaborative project at EMBL Heidelberg and was concluded in the group of Kiran Patil after his move to Cambridge.

This study was funded by the European Commission Horizon 2020, MRC and EMBL.

Reference

Klunemann, M. et al: 'Bioaccumulation of therapeutic drugs by human gut bacteria’, Nature, Sept 2021.

Adapted from a press release by EMBL.

Common medications can accumulate in gut bacteria, a new study has found, altering bacterial function and potentially reducing the medications’ effectiveness.

If we can characterise how people respond depending on the composition of their microbiome, then drug treatments could be individualised

Kiran Patil

Paul Appleton, ̽��ֱ�� of Dundee. Attribution 4.0

Villi in the colon

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

Yes

Licence type:

Attribution

Cooperation is key to success in microbial communities

jg533 — Mon, 04 Jan 2021 16:15:20 +0000

̽��ֱ��results are published today in the journal Nature Microbiology.

̽��ֱ��study used kefir as a model to study metabolic interactions within microbial communities. It is easy to grow, and consists of around 40 different species - providing a ‘Goldilocks zone’ of complexity that is not too small yet not too unwieldy to study in detail. Kefir is composed of ‘grains’ - resembling small pieces of cauliflower - that have fermented in milk to produce a probiotic drink composed of bacteria and yeasts.

̽��ֱ��researchers were surprised to discover that the dominant species of Lactobacillus bacteria found in kefir grains cannot survive on their own in milk. However, the different species work together, feeding on each other’s metabolites in the kefir culture to support each other.

“ ̽��ֱ��kefir grain acts as a ‘base camp’ for the kefir community, from which microbes colonise the milk in a complex, yet organised and cooperative manner,” said Dr Kiran Patil, Director of Research at the ̽��ֱ�� of Cambridge’s MRC Toxicology Unit, group leader at EMBL, and senior author of the study.

̽��ֱ��researchers combined a variety of state-of-the-art methods including metabolomics (studying metabolites’ chemical processes), transcriptomics (studying the genome-produced RNA transcripts), and mathematical modelling. This revealed not only key molecular interaction agents like amino acids, but also the contrasting species dynamics between the grains and the milk.

While scientists know that microorganisms often live in communities and depend on their fellow community members for survival, there was previously very little understanding of how this works. Lab models have historically been limited to two or three different microbial species.

“Kefir microbial communities have many member species, with individual growth patterns that adapt to their current environment. This means fast- and slow-growing species and some that alter their speed according to nutrient availability,” said Sonja Blasche, a postdoc in the Patil group at EMBL and joint first author of the paper.

Kefir is one of the world’s oldest fermented foods and has many purported health benefits, including improving digestion and lowering blood pressure and blood glucose levels.

This phenomenon of microbial cooperation is not limited to kefir. In another paper from Patil’s group, published today in the journal Nature Ecology and Evolution, scientists combined data from thousands of microbial communities across the globe - from soil to the human gut - to understand similar cooperative relationships.

Advanced metabolic modelling showed that the co-occurring groups of bacteria are either highly competitive or highly cooperative. This stark polarisation has not been observed before and sheds light on evolutionary processes that shape microbial ecosystems. While both competitive and cooperative communities are prevalent, the cooperators seem to be more successful: they are more abundant and occupy a more diverse range of habitats.

“We see this phenomenon in kefir, and then we see it’s not limited to kefir,” said Patil. “If you look at the whole world of microbiomes, cooperation is also key to their structure and function.”

References
Patil, K.R. ‘Metabolic cooperation and spatiotemporal niche partitioning in a kefir microbial community.’ Nature Microbiology, Jan 2021. DOI: 10.1038/s41564-020-00816-5.

Patil, K.R. ‘Polarisation of microbial communities between competitive and cooperative metabolism.’ Nature Ecology & Evolution, Jan 2021. DOI: 10.1038/s41559-020-01353-4.

Adapted from a press release by EMBL.

New research from the ̽��ֱ�� of Cambridge and European Molecular Biology Laboratory (EMBL) shows how cooperation among bacterial species allows them to thrive as a community.

If you look at the whole world of microbiomes, cooperation is key to their structure and function.

Kiran Patil

Svorad on Wikimedia Commons

Milk kefir grains with jar of kefir in background

Yes

Licence type:

Attribution