8 ms·

Antibiotics have sex-specific effects on the gut microbiome in rats

81 points by NickRandom 4y ago

stewx 4y ago
Sexual dimorphism is real and has important medical implications.
- deleted 4y ago
  [deleted]
- zionic 4y ago
- makeworld 4y ago
  - cowtools 4y ago
    It is a statement of an obvious truth. It does not need to be "brave". If you find the point true but irrelevant then you would be better off not acknowledging it in the first place.
    - fourseventy 4y ago
  - rhombocombus 4y ago
    It's not brave, it is an important topic. Hundreds of thousands of scientific studies over the last two centuries excluded female subjects because it was too hard to predict their wild female hormones or some other ghastly excuse. Biological sex differences do have important, medically relevant, and poorly understood impacts on health across the lifespan, and unfortunately the field is in its infancy.
  - HL33tibCe7 4y ago
    [deleted]
    - kieselguhr_kid 4y ago
      It actually isn't. You know trans people know this better than anyone else, right?
- CoastalCoder 4y ago
  > Sexual dimorphism is real and has important medical implications. I'm guessing (well, hoping) that everyone agrees that the male/female distinction is medically relevant. E.g., I'd get more from a visit to a urologist than to a gynecologist. I think there's less agreement about the "di" part of "dimorphism". Obviously most humans fall pretty squarely into the "male" vs. "female" categories, but there's less agreement about there being precisely two, clearly delineated categories. Some examples: - hermaphrodites - conjoined twins with different genders (insanely rare, IIUC) - non-heterosexuals and transgender people, to the extent that those characteristics indicate underlying physiological differences
  - HL33tibCe7 4y ago
    Like basically every biological category, the borders of biological sex are blurred. But the vast, vast majority of animals slot into one or the other category. So it’s pretty reasonable to accept the GP’s premise - that sexual dimorphism is real. The exceptions prove the rule. > non-heterosexuals and transgender The discussion here is about biological sex and its medical implications. People who change their gender, or exhibit traits of the opposite gender, aren’t relevant to this conversation. Edit: commenters below me make some good points that I didn’t consider when writing this. I slightly regret this comment now, but can’t delete it at this point. e.g: the fact that transgender people are relevant to this debate because of HRT, which is true, I didn’t think of that.
    - Latty 4y ago
      > The discussion here is about biological sex and its medical implications. People who change their gender, or exhibit traits of the opposite gender, aren’t relevant to this conversation. This seems obviously false. If the link is based around sex hormones, as an example, then being on HRT clearly changes your risk. As with all things, correlation vs causation.
      - deleted 4y ago
        [deleted]
    - 4y ago
- timbo1642 4y ago
  [dead]
- Latty 4y ago
  Which demonstrates the important of distinguishing gender identity from biological sex (i.e: woman from female, man from male). When deciding what pronoun to use, biological sex clearly doesn't matter, when talking to a doctor, it may well matter. We can use the appropriate thing at the appropriate time, just as we do with, say, an adopted child, where most of the time you don't need to distinguish, but when it comes to inheritable disease it clearly matters. Likewise, saying "that female over there" when talking about a trans man is utterly useless to me because it doesn't help me identify them without pre-existing knowledge. Man/woman referring to gender identity clearly makes sense for casual conversation, someone's biological sex is none of your business in most cases. Of course, our increased understanding also says that dimorphism is an oversimplification: the reality is that sexual traits are varied and it is much more of a spectrum, and better understanding of this medically should lead to more personalised medicine that is more effective. This is especially true when it comes to trans people, if the issue is, for example, linked to oestrogen, then HRT can be more relevant than the chromosomes someone has.
  - spinach 4y ago
    - Latty 4y ago
      This is clearly not very useful, or reasonable. People's biological sex is none of your business, so using it when talking about them is not viable. If you see someone who is presenting as a woman, calling them a man because you happen to know they are trans isn't useful to anyone you are communicating with, and it's reminding them of something they'd rather not be bought to the forefront, just as with specifying someone is adopted—it's irrelevant to the conversation in 99% of cases. > If we muddy these words to mean gender, then no one will understand what anyone is saying when talking about health, or sexual orientation, etc. We have trans/cis, male/female, and "biological sex"/"gender identity" to distinguish. We manage to be just fine referring to both biological and adoptive parents as just "parents" and we can still specify where necessary. > If we are talking about a transman, then you can talk about their sex by referring to them as a woman and as a female. Their gender identity is "transman". Even if they appear to look like a man, their sex has not changed. Transman isn't a word, it's incorrect. Trans men are men who are trans, in contrast to cis men. Turning it into a single word would be like calling someone a tallman. No one ever claimed their sex changed, their gender identity is distinct from their sex, that was very much the point.
- deleted 4y ago
  [deleted]
- Bolkan 4y ago
daenz 4y ago
- nikkwong 4y ago
  The differences in treatment effect are in relation to the recipient's biological sex, so it's unnecessary to take gender preference into account.
  - smegsicle 4y ago
    is there any case where it does make sense to take gender "preference" into account? besides pronouns? seems to me that those who insist that gender and sex are distinct also heavily imply that biological sex is mostly meaningless, so its unclear what they actually expect anyone to care about
    - dragonwriter 4y ago
      > seems to me that those who insist that gender and sex are distinct also heavily imply that biological sex is mostly meaningless Gender (either socially ascribed or gender identity, though those two can differ from each other) and biological sex are objectively different things. Most people who value gender identity rather than the particular indicia of biological sex other people prefer as a basis of socially ascribed gender generally view biological sex as a multidimensional space which includes (among other things, some of which are mutable) gender identity, not a simple binary (even if the distribution may be strongly bimodal.) > its unclear what they actually expect anyone to care about Generally, gender identity rather than other factors to the extent that society divides people up by ascribed genders. But also generally a lot less gender segregation, and especially strict binary gender segregation, at all, and when distinctions need to be made to which particular sex- and/or gender-stereotyped traits are relevant, to make distinctions on the particular relevant trait rather than by stereotypical association.
    - Latty 4y ago
      > also heavily imply that biological sex is mostly meaningless This is a puzzling statement to me. The whole concept of being trans requires that there is a distinction between gender identity and biological sex. If the latter didn't matter at all, being trans wouldn't exist. If anything, trans people would surely be the most aware of biological sex and it's impact on them, as they are not happy with it? To me, it's like saying an adoptive parent is trying to imply biological parenthood is meaningless. Surely those who wished to have biological children but could not and adopt instead are often the people most sharply aware of it?
deleted 4y ago
[deleted]
causi 4y ago
The constellation of microbes in the gut did not return to their original, pre-antibiotic compositions in either sex during the duration of the study This makes me wonder why we don't take fecal samples before proscribing humans especially rigorous antibiotics so they can be used to repair the microbiome afterward.
- deleted 4y ago
  [deleted]
- johnnymorgan 4y ago
  I agree, I've always been surprised we do it with animals and vets but not humans and doctors. We know gut flora plays an important role in our health and development. The C.Diff study with fecal matter transplants was an eye opener, and we are definitely overlooking important data. interesting study
- stevenwoo 4y ago
  It was published in 2016 (so may have been superceded by newer studies) but from The Gene: An Intimate History I read that all successful fecal implants to treat Clostridioides difficile required updates every six months to a year from healthy gut biomes - we have not yet figured out how to make a new biome thrive independently, and separately, all probiotic foods have a temporary effect on biomes, they have to be eaten regularly.
- Melatonic 4y ago
  If we even can repair it after the fact? That being said eat your Natto people :-)
WebbWeaver 4y ago
>The antibiotic exposed group (N = 31) included 16 males (M) and 15 females (F), and the control group (N = 17) included nine males and eight females. Small N but as a layman it could be potentially significant. Perhaps hormonal changes could be monitored in fecal microbiomes.
- jonlucc 4y ago
  Honestly, for PCR, this is a larger N than I would guess is needed. In general, rats kept in constant conditions don't have a ton of variation, even in fairly high-sensitivity assays. I would expect a lot more samples if you were sampling wild rats from the subway system. I recently looked at a disease course over time for several hundred genes. I only used 6 animals per time point, and both the disease mice and non-disease mice have very little inter-mouse variation at each time point for the vast majority of the genes.
  - deleted 4y ago
    [deleted]
jonlucc 4y ago
I don't work with antibiotics or directly with the microbiome, but I have some questions about how these rats were housed. As background, I work in autoimmune pharma discovery, and my role is primarily with rodent models of disease. I also sit on my institution's IACUC, so I see a lot of other departments' protocols. One thing that has become common in some facilities is housing males and females in separate rooms. Female mice and rats get pretty stressed when you house them next to males, or when you handle males first and then females after. This is a damned-if-you-do-damned-if-you-don't situation, because either these rats were housed in different rooms, which could cause microbiome differences, or they were housed together, which could cause stress, which could cause microbiome differences. I think overall, this study is reasonable, and the fact that it confirms previous studies bolsters the hypothesis, but I'm not sure how you actually tease these out without a mechanistic proposition. Lastly, based on my experience, there's something a little odd about their weight data. We use weight as a loose proxy for wellness, so it's regularly measured. The body weight for both the males and females are about 30g higher than I'd expect for this age (8 woa). Most rats and mice are very consistent weight for a given age, and this is just a minor red flag, but it makes me wonder more about their husbandry. Just my 2 cents.
- sytelus 4y ago
  I have a question on which manufacturer sponsored this study.
  - jonlucc 4y ago
    Well based on their materials and methods, the antibiotics were all ordered from Sigma, which is not a pharma company, and I doubt they stand to gain much from the study. What kind of manufacture do you think benefits from this outcome?
mountainb 4y ago
Rats are not humans and observed effects in rats and other animals can only occasionally be replicated in humans. The main thing that this does is make it possible to justify further studies, eventually in humans, at which point the issue can be investigated in more depth.

81 points by NickRandom 4y ago

stewx 4y ago

Sexual dimorphism is real and has important medical implications.

deleted 4y ago
[deleted]
zionic 4y ago
makeworld 4y ago
- cowtools 4y ago
  It is a statement of an obvious truth. It does not need to be "brave". If you find the point true but irrelevant then you would be better off not acknowledging it in the first place.
  - fourseventy 4y ago
- rhombocombus 4y ago
  It's not brave, it is an important topic. Hundreds of thousands of scientific studies over the last two centuries excluded female subjects because it was too hard to predict their wild female hormones or some other ghastly excuse. Biological sex differences do have important, medically relevant, and poorly understood impacts on health across the lifespan, and unfortunately the field is in its infancy.
- HL33tibCe7 4y ago
  [deleted]
  - kieselguhr_kid 4y ago
    It actually isn't. You know trans people know this better than anyone else, right?
CoastalCoder 4y ago
> Sexual dimorphism is real and has important medical implications. I'm guessing (well, hoping) that everyone agrees that the male/female distinction is medically relevant. E.g., I'd get more from a visit to a urologist than to a gynecologist. I think there's less agreement about the "di" part of "dimorphism". Obviously most humans fall pretty squarely into the "male" vs. "female" categories, but there's less agreement about there being precisely two, clearly delineated categories. Some examples: - hermaphrodites - conjoined twins with different genders (insanely rare, IIUC) - non-heterosexuals and transgender people, to the extent that those characteristics indicate underlying physiological differences
- HL33tibCe7 4y ago
  Like basically every biological category, the borders of biological sex are blurred. But the vast, vast majority of animals slot into one or the other category. So it’s pretty reasonable to accept the GP’s premise - that sexual dimorphism is real. The exceptions prove the rule. > non-heterosexuals and transgender The discussion here is about biological sex and its medical implications. People who change their gender, or exhibit traits of the opposite gender, aren’t relevant to this conversation. Edit: commenters below me make some good points that I didn’t consider when writing this. I slightly regret this comment now, but can’t delete it at this point. e.g: the fact that transgender people are relevant to this debate because of HRT, which is true, I didn’t think of that.
  - Latty 4y ago
    > The discussion here is about biological sex and its medical implications. People who change their gender, or exhibit traits of the opposite gender, aren’t relevant to this conversation. This seems obviously false. If the link is based around sex hormones, as an example, then being on HRT clearly changes your risk. As with all things, correlation vs causation.
    - deleted 4y ago
      [deleted]
  - 4y ago
timbo1642 4y ago
[dead]
Latty 4y ago
Which demonstrates the important of distinguishing gender identity from biological sex (i.e: woman from female, man from male). When deciding what pronoun to use, biological sex clearly doesn't matter, when talking to a doctor, it may well matter. We can use the appropriate thing at the appropriate time, just as we do with, say, an adopted child, where most of the time you don't need to distinguish, but when it comes to inheritable disease it clearly matters. Likewise, saying "that female over there" when talking about a trans man is utterly useless to me because it doesn't help me identify them without pre-existing knowledge. Man/woman referring to gender identity clearly makes sense for casual conversation, someone's biological sex is none of your business in most cases. Of course, our increased understanding also says that dimorphism is an oversimplification: the reality is that sexual traits are varied and it is much more of a spectrum, and better understanding of this medically should lead to more personalised medicine that is more effective. This is especially true when it comes to trans people, if the issue is, for example, linked to oestrogen, then HRT can be more relevant than the chromosomes someone has.
- spinach 4y ago
  - Latty 4y ago
    This is clearly not very useful, or reasonable. People's biological sex is none of your business, so using it when talking about them is not viable. If you see someone who is presenting as a woman, calling them a man because you happen to know they are trans isn't useful to anyone you are communicating with, and it's reminding them of something they'd rather not be bought to the forefront, just as with specifying someone is adopted—it's irrelevant to the conversation in 99% of cases. > If we muddy these words to mean gender, then no one will understand what anyone is saying when talking about health, or sexual orientation, etc. We have trans/cis, male/female, and "biological sex"/"gender identity" to distinguish. We manage to be just fine referring to both biological and adoptive parents as just "parents" and we can still specify where necessary. > If we are talking about a transman, then you can talk about their sex by referring to them as a woman and as a female. Their gender identity is "transman". Even if they appear to look like a man, their sex has not changed. Transman isn't a word, it's incorrect. Trans men are men who are trans, in contrast to cis men. Turning it into a single word would be like calling someone a tallman. No one ever claimed their sex changed, their gender identity is distinct from their sex, that was very much the point.
deleted 4y ago
[deleted]
Bolkan 4y ago

daenz 4y ago

nikkwong 4y ago
The differences in treatment effect are in relation to the recipient's biological sex, so it's unnecessary to take gender preference into account.
- smegsicle 4y ago
  is there any case where it does make sense to take gender "preference" into account? besides pronouns? seems to me that those who insist that gender and sex are distinct also heavily imply that biological sex is mostly meaningless, so its unclear what they actually expect anyone to care about
  - dragonwriter 4y ago
    > seems to me that those who insist that gender and sex are distinct also heavily imply that biological sex is mostly meaningless Gender (either socially ascribed or gender identity, though those two can differ from each other) and biological sex are objectively different things. Most people who value gender identity rather than the particular indicia of biological sex other people prefer as a basis of socially ascribed gender generally view biological sex as a multidimensional space which includes (among other things, some of which are mutable) gender identity, not a simple binary (even if the distribution may be strongly bimodal.) > its unclear what they actually expect anyone to care about Generally, gender identity rather than other factors to the extent that society divides people up by ascribed genders. But also generally a lot less gender segregation, and especially strict binary gender segregation, at all, and when distinctions need to be made to which particular sex- and/or gender-stereotyped traits are relevant, to make distinctions on the particular relevant trait rather than by stereotypical association.
  - Latty 4y ago
    > also heavily imply that biological sex is mostly meaningless This is a puzzling statement to me. The whole concept of being trans requires that there is a distinction between gender identity and biological sex. If the latter didn't matter at all, being trans wouldn't exist. If anything, trans people would surely be the most aware of biological sex and it's impact on them, as they are not happy with it? To me, it's like saying an adoptive parent is trying to imply biological parenthood is meaningless. Surely those who wished to have biological children but could not and adopt instead are often the people most sharply aware of it?

deleted 4y ago

[deleted]

causi 4y ago

The constellation of microbes in the gut did not return to their original, pre-antibiotic compositions in either sex during the duration of the study This makes me wonder why we don't take fecal samples before proscribing humans especially rigorous antibiotics so they can be used to repair the microbiome afterward.

deleted 4y ago
[deleted]
johnnymorgan 4y ago
I agree, I've always been surprised we do it with animals and vets but not humans and doctors. We know gut flora plays an important role in our health and development. The C.Diff study with fecal matter transplants was an eye opener, and we are definitely overlooking important data. interesting study
stevenwoo 4y ago
It was published in 2016 (so may have been superceded by newer studies) but from The Gene: An Intimate History I read that all successful fecal implants to treat Clostridioides difficile required updates every six months to a year from healthy gut biomes - we have not yet figured out how to make a new biome thrive independently, and separately, all probiotic foods have a temporary effect on biomes, they have to be eaten regularly.
Melatonic 4y ago
If we even can repair it after the fact? That being said eat your Natto people :-)

WebbWeaver 4y ago

>The antibiotic exposed group (N = 31) included 16 males (M) and 15 females (F), and the control group (N = 17) included nine males and eight females. Small N but as a layman it could be potentially significant. Perhaps hormonal changes could be monitored in fecal microbiomes.

jonlucc 4y ago
Honestly, for PCR, this is a larger N than I would guess is needed. In general, rats kept in constant conditions don't have a ton of variation, even in fairly high-sensitivity assays. I would expect a lot more samples if you were sampling wild rats from the subway system. I recently looked at a disease course over time for several hundred genes. I only used 6 animals per time point, and both the disease mice and non-disease mice have very little inter-mouse variation at each time point for the vast majority of the genes.
- deleted 4y ago
  [deleted]

jonlucc 4y ago

I don't work with antibiotics or directly with the microbiome, but I have some questions about how these rats were housed. As background, I work in autoimmune pharma discovery, and my role is primarily with rodent models of disease. I also sit on my institution's IACUC, so I see a lot of other departments' protocols. One thing that has become common in some facilities is housing males and females in separate rooms. Female mice and rats get pretty stressed when you house them next to males, or when you handle males first and then females after. This is a damned-if-you-do-damned-if-you-don't situation, because either these rats were housed in different rooms, which could cause microbiome differences, or they were housed together, which could cause stress, which could cause microbiome differences. I think overall, this study is reasonable, and the fact that it confirms previous studies bolsters the hypothesis, but I'm not sure how you actually tease these out without a mechanistic proposition. Lastly, based on my experience, there's something a little odd about their weight data. We use weight as a loose proxy for wellness, so it's regularly measured. The body weight for both the males and females are about 30g higher than I'd expect for this age (8 woa). Most rats and mice are very consistent weight for a given age, and this is just a minor red flag, but it makes me wonder more about their husbandry. Just my 2 cents.

sytelus 4y ago
I have a question on which manufacturer sponsored this study.
- jonlucc 4y ago
  Well based on their materials and methods, the antibiotics were all ordered from Sigma, which is not a pharma company, and I doubt they stand to gain much from the study. What kind of manufacture do you think benefits from this outcome?

mountainb 4y ago

Rats are not humans and observed effects in rats and other animals can only occasionally be replicated in humans. The main thing that this does is make it possible to justify further studies, eventually in humans, at which point the issue can be investigated in more depth.