All Gut Bacteria Dangerous, Its Endotoxin Drives Liver Cancer; Antibiotics Cure

[snacks]

Is it below sea level yet? It happens a lot.

I've moved my residence to an airplane to allow my drooping stomach to benefit from high altitude life

 

[SOMO]

Every time I see long term low-dose use of antiboitics advocated on this forum my stomach drops a bit. Please just use oreg oil or something

Most of them are quite safe.

Also oregano oil tastes bad. Synthetic antibiotics are superior broad spectrum, meaning they kill a wider variety of microbes.

 

[TheBeard]

Every time I see long term low-dose use of antiboitics advocated on this forum my stomach drops a bit. Please just use oreg oil or something

Why?

I'd rather endure the slight abx toxicity than lose my liver and my gut over an endotoxin overload.

 

[Frankdee20]

Bactrim should be reserved for when you have a life-threatening infection or a long-term persistent infection that is not going away.

Yeah well, that’s usually what I do with antibiotics.... only when absolutely essential to use

 

[Amazoniac]

Came across this:

- Total Lipopolysaccharide from the Human Gut Microbiome Silences Toll-Like Receptor Signaling

"Here we formally demonstrate that the total LPS produced by the human gut microbiome not only is itself nonimmunogenic but also inhibits TLR4-dependent cytokine production (Fig. 1B to F)."

"[..]we directly extracted the total LPS from fecal samples from healthy adult humans and found that the LPS produced by the consortium of gut-resident microbes potently antagonizes the host TLR4 pathway."

"Using metagenomic sequencing, we further delineated strain level contributions to the gut LPS pool and found that numerous other members of the order Bacteroidales, which are the dominant Gram-negative bacteria in the healthy human gut microbiome (12), produce antagonistic forms of LPS, thus driving immune silencing for the entire microbial community. These findings undermine the current accepted paradigm that gut microbial communities possess a robust TLR4 signaling capacity against which the immune system needs to be heavily tolerized (13)."

"Previous publications have demonstrated that distinct structural features of the lipid A domain, produced by a few bacterial species, interfere with proper TLR4-MD2 signaling via competitive inhibition (17, 19). The exact mechanism of signaling inhibition by feces-derived LPS has not been demonstrated in this study but is likely to be identical to previously described mechanisms."

"Our findings also shed new light on a number of discoveries made in recent years that suggest a link between the inflammatory stimulation arising from the intestinal lumen and local or peripheral inflammatory disorders. Inflammatory bowel disease (IBD) has been associated with a bloom of Proteobacteria (26, 27). Interestingly, treatment with the aminoglycoside antibiotic gentamicin reduces the abundance of Proteobacteria and results in a dominance of the gut flora by Bacteroidetes, leading to protection from colitis in a murine model of IBD. Conversely, vancomycin treatment has been shown to favor an increase in Proteobacteria and does not prevent disease (28, 29). While the specific role of inflammatory LPS in the etiology and recovery of IBD remains to be elucidated, it is possible that differences in LPS immunogenicity between Bacteroidetes and Proteobacteria underlie these observations."​

 

[TheBeard]

Came across this:

- Total Lipopolysaccharide from the Human Gut Microbiome Silences Toll-Like Receptor Signaling

"Here we formally demonstrate that the total LPS produced by the human gut microbiome not only is itself nonimmunogenic but also inhibits TLR4-dependent cytokine production (Fig. 1B to F)."

"[..]we directly extracted the total LPS from fecal samples from healthy adult humans and found that the LPS produced by the consortium of gut-resident microbes potently antagonizes the host TLR4 pathway."

"Using metagenomic sequencing, we further delineated strain level contributions to the gut LPS pool and found that numerous other members of the order Bacteroidales, which are the dominant Gram-negative bacteria in the healthy human gut microbiome (12), produce antagonistic forms of LPS, thus driving immune silencing for the entire microbial community. These findings undermine the current accepted paradigm that gut microbial communities possess a robust TLR4 signaling capacity against which the immune system needs to be heavily tolerized (13)."

"Previous publications have demonstrated that distinct structural features of the lipid A domain, produced by a few bacterial species, interfere with proper TLR4-MD2 signaling via competitive inhibition (17, 19). The exact mechanism of signaling inhibition by feces-derived LPS has not been demonstrated in this study but is likely to be identical to previously described mechanisms."

"Our findings also shed new light on a number of discoveries made in recent years that suggest a link between the inflammatory stimulation arising from the intestinal lumen and local or peripheral inflammatory disorders. Inflammatory bowel disease (IBD) has been associated with a bloom of Proteobacteria (26, 27). Interestingly, treatment with the aminoglycoside antibiotic gentamicin reduces the abundance of Proteobacteria and results in a dominance of the gut flora by Bacteroidetes, leading to protection from colitis in a murine model of IBD. Conversely, vancomycin treatment has been shown to favor an increase in Proteobacteria and does not prevent disease (28, 29). While the specific role of inflammatory LPS in the etiology and recovery of IBD remains to be elucidated, it is possible that differences in LPS immunogenicity between Bacteroidetes and Proteobacteria underlie these observations."​

Thanks

 

[Korven]

Came across this:

- Total Lipopolysaccharide from the Human Gut Microbiome Silences Toll-Like Receptor Signaling

"Here we formally demonstrate that the total LPS produced by the human gut microbiome not only is itself nonimmunogenic but also inhibits TLR4-dependent cytokine production (Fig. 1B to F)."

"[..]we directly extracted the total LPS from fecal samples from healthy adult humans and found that the LPS produced by the consortium of gut-resident microbes potently antagonizes the host TLR4 pathway."

"Using metagenomic sequencing, we further delineated strain level contributions to the gut LPS pool and found that numerous other members of the order Bacteroidales, which are the dominant Gram-negative bacteria in the healthy human gut microbiome (12), produce antagonistic forms of LPS, thus driving immune silencing for the entire microbial community. These findings undermine the current accepted paradigm that gut microbial communities possess a robust TLR4 signaling capacity against which the immune system needs to be heavily tolerized (13)."

"Previous publications have demonstrated that distinct structural features of the lipid A domain, produced by a few bacterial species, interfere with proper TLR4-MD2 signaling via competitive inhibition (17, 19). The exact mechanism of signaling inhibition by feces-derived LPS has not been demonstrated in this study but is likely to be identical to previously described mechanisms."

"Our findings also shed new light on a number of discoveries made in recent years that suggest a link between the inflammatory stimulation arising from the intestinal lumen and local or peripheral inflammatory disorders. Inflammatory bowel disease (IBD) has been associated with a bloom of Proteobacteria (26, 27). Interestingly, treatment with the aminoglycoside antibiotic gentamicin reduces the abundance of Proteobacteria and results in a dominance of the gut flora by Bacteroidetes, leading to protection from colitis in a murine model of IBD. Conversely, vancomycin treatment has been shown to favor an increase in Proteobacteria and does not prevent disease (28, 29). While the specific role of inflammatory LPS in the etiology and recovery of IBD remains to be elucidated, it is possible that differences in LPS immunogenicity between Bacteroidetes and Proteobacteria underlie these observations."​

So this means that modulating the gut microbiome/fixing dysbiosis is probably a better idea than to "nuke them all"?

If you take antibiotics that kill off helpful TLR4-silencing bacteria you just made yourself more endotoxic and sick. This matches my own experience with antibiotics, natural or not. I feel good for a while then I feel worse.

 

[Amazoniac]

So this means that modulating the gut microbiome/fixing dysbiosis is probably a better idea than to "nuke them all"?

If you take antibiotics that kill off helpful TLR4-silencing bacteria you just made yourself more endotoxic and sick. This matches my own experience with antibiotics, natural or not. I feel good for a while then I feel worse.

Once sterility is out of question, the options that we is left with is having the niches occupied by friendly or unfriendly bacteria. If it's the unfriendly ones that predominate, it's because they're being promoted by an inflammatory environment or because they're evading immunity somehow. Since it's of greater importance to address the threat, they have to be more resistant than the friendly ones to be able to withstand competition and attacks, so if we hit them all with a broad-spectrum antibiotic and the immune system doesn't take advantage of the window of opportunity, we'll be selecting the unfriendly ones.

Sometimes the best thing to do is to eat what (you crave but) ills you because this is where most of the therapeutic potential lies, the person has to persist but it can't be overwhelming for obvious reasons. Once there's the strong signal, it's the immune system that has to be supported; it can be fever, sun exposure, and so on. I think that ingested poison A and venom D can be made active locally in the gut, if there's a significant problem, the activation may become inappropriate for being wasteful on resources, the reaction is exaggerated, the body throws all in.

During the antibiotic course, some problematic foods have to be consumed to reveal the infection.

 

[Kvothe]

Came across this:

- Total Lipopolysaccharide from the Human Gut Microbiome Silences Toll-Like Receptor Signaling

"Here we formally demonstrate that the total LPS produced by the human gut microbiome not only is itself nonimmunogenic but also inhibits TLR4-dependent cytokine production (Fig. 1B to F)."

"[..]we directly extracted the total LPS from fecal samples from healthy adult humans and found that the LPS produced by the consortium of gut-resident microbes potently antagonizes the host TLR4 pathway."

"Using metagenomic sequencing, we further delineated strain level contributions to the gut LPS pool and found that numerous other members of the order Bacteroidales, which are the dominant Gram-negative bacteria in the healthy human gut microbiome (12), produce antagonistic forms of LPS, thus driving immune silencing for the entire microbial community. These findings undermine the current accepted paradigm that gut microbial communities possess a robust TLR4 signaling capacity against which the immune system needs to be heavily tolerized (13)."

"Previous publications have demonstrated that distinct structural features of the lipid A domain, produced by a few bacterial species, interfere with proper TLR4-MD2 signaling via competitive inhibition (17, 19). The exact mechanism of signaling inhibition by feces-derived LPS has not been demonstrated in this study but is likely to be identical to previously described mechanisms."

"Our findings also shed new light on a number of discoveries made in recent years that suggest a link between the inflammatory stimulation arising from the intestinal lumen and local or peripheral inflammatory disorders. Inflammatory bowel disease (IBD) has been associated with a bloom of Proteobacteria (26, 27). Interestingly, treatment with the aminoglycoside antibiotic gentamicin reduces the abundance of Proteobacteria and results in a dominance of the gut flora by Bacteroidetes, leading to protection from colitis in a murine model of IBD. Conversely, vancomycin treatment has been shown to favor an increase in Proteobacteria and does not prevent disease (28, 29). While the specific role of inflammatory LPS in the etiology and recovery of IBD remains to be elucidated, it is possible that differences in LPS immunogenicity between Bacteroidetes and Proteobacteria underlie these observations."​

The general assumption of their paper seems to be that "immune silencing" LPS is somehow not dangerous or even protective. This, in turn, is connected to their theory that bacteroides are somehow generally more favorable than firmicutes. This correlational is highly debatable and there are probably as many studies claiming the opposite. Their conclusion regarding the protective effect of bacteroides-LPS seems surprising especially since they directly cite a paper that is contradicting their idea of beneficial LPS.

Variation in Microbiome LPS Immunogenicity Contributes to Autoimmunity in Humans - ScienceDirect

"According to the hygiene hypothesis, the increasing incidence of autoimmune diseases in western countries may be explained by changes in early microbial exposure, leading to altered immune maturation. We followed gut microbiome development from birth until age three in 222 infants in Northern Europe, where early-onset autoimmune diseases are common in Finland and Estonia but are less prevalent in Russia. We found that Bacteroides species are lowly abundant in Russians but dominate in Finnish and Estonian infants. Therefore, their lipopolysaccharide (LPS) exposures arose primarily from Bacteroides rather than from Escherichia coli, which is a potent innate immune activator. We show that Bacteroides LPS is structurally distinct from E. coli LPS and inhibits innate immune signaling and endotoxin tolerance; furthermore, unlike LPS from E. coli, B. dorei LPS does not decrease incidence of autoimmune diabetes in non-obese diabetic mice. Early colonization by immunologically silencing microbiota may thus preclude aspects of immune education."

"Importantly, we show that injection of an immunogenic subtype of LPS from E. coli can both elicit endotoxin tolerance in vivo in NOD mice and decrease the incidence of diabetes in these mice. These effects were not observed with LPS from B. dorei. Our observations suggest that microbiome-derived LPS could impact long-term immunosuppressive mechanisms in more complex ways than has been previously appreciated."​

 

[TheBeard]

Once sterility is out of question, the options that we is left with is having the niches occupied by friendly or unfriendly bacteria. If it's the unfriendly ones that predominate, it's because they're being promoted by an inflammatory environment or because they're evading immunity somehow. Since it's of greater importance to address the threat, they have to be more resistant than the friendly ones to be able to withstand competition and attacks, so if we hit them all with a broad-spectrum antibiotic and the immune system doesn't take advantage of the window of opportunity, we'll be selecting the unfriendly ones.

Sometimes the best thing to do is to eat what (you crave but) ills you because this is where most of the therapeutic potential lies, the person has to persist but it can't be overwhelming for obvious reasons. Once there's the strong signal, it's the immune system that has to be supported; it can be fever, sun exposure, and so on. I think that ingested poison A and venom D can be made active locally in the gut, if there's a significant problem, the activation may become inappropriate for being wasteful on resources, the reaction is exaggerated, the body throws all in.

During the antibiotic course, some problematic foods have to be consumed to reveal the infection.

Counterintuitive but I see where you're coming from

 

[TheBeard]

So this means that modulating the gut microbiome/fixing dysbiosis is probably a better idea than to "nuke them all"?

If you take antibiotics that kill off helpful TLR4-silencing bacteria you just made yourself more endotoxic and sick. This matches my own experience with antibiotics, natural or not. I feel good for a while then I feel worse.

Same here. Haven't found a successful long lasting protocole.

 

[Maljam]

Same here. Haven't found a successful long lasting protocole.

Why do you recommend other people take antibiotics if you have only found it a temporary fix yourself?

 

[Amazoniac]

The general assumption of their paper seems to be that "immune silencing" LPS is somehow not dangerous or even protective. This, in turn, is connected to their theory that bacteroides are somehow generally more favorable than firmicutes. This correlational is highly debatable and there are probably as many studies claiming the opposite. Their conclusion regarding the protective effect of bacteroides-LPS seems surprising especially since they directly cite a paper that is contradicting their idea of beneficial LPS.

Variation in Microbiome LPS Immunogenicity Contributes to Autoimmunity in Humans - ScienceDirect

"According to the hygiene hypothesis, the increasing incidence of autoimmune diseases in western countries may be explained by changes in early microbial exposure, leading to altered immune maturation. We followed gut microbiome development from birth until age three in 222 infants in Northern Europe, where early-onset autoimmune diseases are common in Finland and Estonia but are less prevalent in Russia. We found that Bacteroides species are lowly abundant in Russians but dominate in Finnish and Estonian infants. Therefore, their lipopolysaccharide (LPS) exposures arose primarily from Bacteroides rather than from Escherichia coli, which is a potent innate immune activator. We show that Bacteroides LPS is structurally distinct from E. coli LPS and inhibits innate immune signaling and endotoxin tolerance; furthermore, unlike LPS from E. coli, B. dorei LPS does not decrease incidence of autoimmune diabetes in non-obese diabetic mice. Early colonization by immunologically silencing microbiota may thus preclude aspects of immune education."

"Importantly, we show that injection of an immunogenic subtype of LPS from E. coli can both elicit endotoxin tolerance in vivo in NOD mice and decrease the incidence of diabetes in these mice. These effects were not observed with LPS from B. dorei. Our observations suggest that microbiome-derived LPS could impact long-term immunosuppressive mechanisms in more complex ways than has been previously appreciated."​

That's their other publication and it motivated their next investigations, they certainly had it in mind. Their interest was in understanding how these contrasting responses to different LPS could contribute to tolerance development in the gut and in challenging some existing notions, not in promoting suppression at all costs.

"While the ability for humans to host a complex microbial ecosystem is an essential property of life, the mechanisms allowing for immune tolerance of such a large microbial load are not completely understood and are currently the focus of intense research. This study shows that an important proinflammatory pathway that is commonly triggered by pathogenic bacteria upon interaction with the host is, in fact, actively repressed by the bacteria of the gut microbiome, supporting the idea that beneficial microbes themselves contribute to the immune tolerance in support of homeostasis. These findings are important for two reasons. First, many currently assume that proinflammatory signaling by lipopolysaccharide is a fundamental feature of the gut flora. This assumption influences greatly how host-microbiome interactions are theoretically modeled but also how they are experimentally studied, by using robust TLR signaling conditions to simulate commensals. Second, elucidation of the mechanisms that support host-microbe tolerance is key to the development of therapeutics for both intestinal and systemic inflammatory disorders."​

Regarding that last quoted paragraph, in their experiment, injection of LPS from B. dorei didn't make animals worse, it was comparable to a control group, it was the stimulatory effect of E. coli's LPS considered protective.

Infants may also be a special case in terms of immunity because they're still under marked adaptation to the environment. However, messing up with signalling is always risky, even in adults, but many people are desperately curbing inflammation for finding relief in doing so, this is far from peace. On the other hand, infections that aren't cleared might force the body to develop tolerance, so occasional shocks where the immune system freaks out and goes through transient intolerance should be protective, but it's not something that can be sustained.

 

[gaze]

Sometimes the best thing to do is to eat what (you crave but) ills you because this is where most of the therapeutic potential lies

is this your way of saying people should eat starch? just joking..

Dont you think D supplementation would provide enough window of opportunity to find some sort of appetite? Any metabolic stimulant can be harsh, but Vitamin D supplement seems to be less so of a stimulant and rater a push in the right direction, enough to go forward at least. If nothing is being digested properly, cravings are out the window, because there is a deficiency of everything, but the serotonin creates an anorexic condition of no real appetite.

 

[Kvothe]

That's their other publication and it motivated their next investigations, they certainly had it in mind. Their interest was in understanding how these contrasting responses to different LPS could contribute to tolerance development in the gut and in challenging some existing notions, not in promoting suppression at all costs.

"While the ability for humans to host a complex microbial ecosystem is an essential property of life, the mechanisms allowing for immune tolerance of such a large microbial load are not completely understood and are currently the focus of intense research. This study shows that an important proinflammatory pathway that is commonly triggered by pathogenic bacteria upon interaction with the host is, in fact, actively repressed by the bacteria of the gut microbiome, supporting the idea that beneficial microbes themselves contribute to the immune tolerance in support of homeostasis. These findings are important for two reasons. First, many currently assume that proinflammatory signaling by lipopolysaccharide is a fundamental feature of the gut flora. This assumption influences greatly how host-microbiome interactions are theoretically modeled but also how they are experimentally studied, by using robust TLR signaling conditions to simulate commensals. Second, elucidation of the mechanisms that support host-microbe tolerance is key to the development of therapeutics for both intestinal and systemic inflammatory disorders."​

Regarding that last quoted paragraph, in their experiment, injection of LPS from B. dorei didn't make animals worse, it was comparable to a control group, it was the stimulatory effect of E. coli's LPS considered protective.

Infants may also be a special case in terms of immunity because they're still under marked adaptation to the environment. However, messing up with signalling is always risky, even in adults, but many people are desperately curbing inflammation for finding relief in doing so, this is far from peace. On the other hand, infections that aren't cleared might force the body to develop tolerance, so occasional shocks where the immune system freaks out and goes through transient intolerance should be protective, but it's not something that can be sustained.

Their findings are interesting and certainly warrant further inquiry. Nevertheless, I would be very cautious to draw any conclusions from this, not only because of their own study showing that this "beneficial" ratio of LPS producing bacteroides to strains like e.coli is associated with autoimmunity in children. Endotoxin remains endotoxin, and I somehow doubt that the small variations in the lipid A component suddenly renders it neutral or beneficial. Something doesn't have to elicit a strong inflammatory immune reaction in order to be toxic. I am somehow reminded of the study showing soluble fiber to normalize all inflammatory blood parameters in rats simply to later reveal that all of them had rampant liver carcinomas. Some more long-term in vivo studies would be needed to confirm some of their suspicions. At the moment, I simply can't understand why they can frame the "new endotoxin" as beneficial when it is associated with autoimmune diseases in humans, and amplifies the incidence of diabetes in animal models.

 

[Amazoniac]

is this your way of saying people should eat starch? just joking..

Dont you think D supplementation would provide enough window of opportunity to find some sort of appetite? Any metabolic stimulant can be harsh, but Vitamin D supplement seems to be less so of a stimulant and rater a push in the right direction, enough to go forward at least. If nothing is being digested properly, cravings are out the window, because there is a deficiency of everything, but the serotonin creates an anorexic condition of no real appetite.

Yes, it can intoxicate the victims on the right direction, but it's common for it to be used carelessly. It only takes one cofactor mismatch to constrain. For example, if excretion stayed the same, the oral absorption of venom D is high whereas magnesium is low, how many are respecting this limitation or can keep up with it? It's similar to thyroid supplements, if the person doesn't start responding, things will get worse on insistence.

Their findings are interesting and certainly warrant further inquiry. Nevertheless, I would be very cautious to draw any conclusions from this, not only because of their own study showing that this "beneficial" ratio of LPS producing bacteroides to strains like e.coli is associated with autoimmunity in children. Endotoxin remains endotoxin, and I somehow doubt that the small variations in the lipid A component suddenly renders it neutral or beneficial. Something doesn't have to elicit a strong inflammatory immune reaction in order to be toxic. I am somehow reminded of the study showing soluble fiber to normalize all inflammatory blood parameters in rats simply to later reveal that all of them had rampant liver carcinomas. Some more long-term in vivo studies would be needed to confirm some of their suspicions. At the moment, I simply can't understand why they can frame the "new endotoxin" as beneficial when it is associated with autoimmune diseases in humans, and amplifies the incidence of diabetes in animal models.

What's there to worry?

Spoiler

"We thank Tiffany Poon and Scott Steelman (Broad Institute) for help in sequence production and sample management, Leon Murphy (Novartis) for help with experimental design, Katriina Koski and Matti Koski (University of Helsinki) for the coordination and database work in the DIABIMMUNE study, Chengwei Luo (Broad Institute) for help in the strain analysis, and Natalia Nedelsky (Massachusetts General Hospital) for editorial help in writing and figure generation. T.V. was supported by funding from JDRF and Hecse (Helsinki Doctoral Programme in Computer Science). H.L. and T.V. were supported by funding from the Academy of Finland Center of Excellence in Systems Immunology and Physiology Research. A.D.K received support as the Merck Fellow of the Helen Hay Whitney Foundation and as the Lawrence H. Summers Fellow of the Broad Institute. M.K. was supported by the European Union Seventh Framework Programme FP7/2007-2013 (202063) and the Academy of Finland Centre of Excellence in Molecular Systems Immunology and Physiology Research (250114). R.J.X. was supported by funding from JDRF, grants from the NIH (U54 DK102557, R01 DK092405, and P30 DK043351), funding from the Leona M. and Harry B. Helmsley Charitable Trust, and funding from the Center for Microbiome Informatics and Therapeutics at MIT."

But if annihilation isn't an option because there won't be void, in general, modulation to select those that are less inflammatory is a beneficial move.
- Like Cures Like: Pharmacological Activity of Anti-Inflammatory Lipopolysaccharides From Gut Microbiome

It's important to be aware that not all LPS trigger the same reaction, but just as important is to know when the decrease in potency is a result of their evolution to elicit a milder response for them to thrive, which may well be the case for the germs in question here.

 

[gaze]

Yes, it can intoxicate the victims on the right direction, but it's common for it to be used carelessly. It only takes one cofactor mismatch to constrain. For example, if excretion stayed the same, the oral absorption of venom D is high whereas magnesium is low, how many are respecting this limitation or can keep up with it? It's similar to thyroid supplements, if the person doesn't start responding, things will get worse on insistence.

What's there to worry?

​

​

But in a degenerative condition, any food can make another imbalance worse. at least vitamin D, up until a certain point, helps retention and a slightly homeostatic effect. ok course past the point of retention and into leeching is bad, but most people at least have a little bit of calcium and magnesium in their diets, even really bad diets, so the increased absorption of those helps in the right direction, where as trying to eat more food unless perfect, will cause some other problem : for example, a bowl of white rice and steak will make calcium, magnesium, and b1 deficiencies worse, some potatoes makes other vitamins worse by endotoxin from lack of calcium and magnesium, basically when your degenerating, you need food and minerals and vitamins, non of which get absorbed properly. the small intoxication of vitamin D, at least can help you go from one meal to the next in a stable condition, much better than you would at levels under 20 or so. Thats why I think ray always recommends milk, orange juice, and "have you checked your vitamin D" because when your falling backwards, everything is making the fall worse except highly easy to digest and nutrient rich foods (except liver), along with normalizing vitamin D levels.



I think Rays opinion in that video is in a similar mode of thought

 

[Amazoniac]

- The human gut microbiota is neither an organ nor a commensal

"To have a gut microbiota, it means to have available a great collection of exclusive enzymes, different from those of the host, although similar in their functions. Thus, besides to be a catabolic system [] for its additional and complementary role in digestion, the gut microbiota may be seen as a community of cells capable of cooperating in many metabolic reactions needed for the biotransformation of foreign molecules that we cannot metabolize easily enough, such as drugs, xenobiotics, polyphenols, antibiotics, and chemical food additives. To understand the metabolic importance of gut microbiota, it is enough to know that there are maybe 3000 cytochrome P450 enzymes in gut bacteria, while the correspondent CYP450 in humans are only 57 [33].

The availability of such a large number of microbial enzymes capable of modifying molecules already in the intestine, before reaching the liver, is of great importance, even if it creates problems in taking oral medications. Indeed, the presence of human gut microbiota should be taken into account during therapeutic intervention, as the microbiota can metabolize drugs and as therapy itself may affect both the metabolic activity of the gut microbiota and its composition [30].

On the other hand, the fact that the microbiota performs useful functions for the intestine and liver is not surprising, considering that both are digestive organs and that both, the hepatocytes and the intestinal epithelium have in common the same developmental origin from the ventral foregut endoderm."

- Anatomical plane - Wikipedia
- Embriology: The development of the gastrointestinal tract | Medical Animations​

"The shift of the composition of the microbiota from obligate to facultative anaerobic bacteria is another consequence of dietary changes, such as the adoption of an energy‐dense Westernized diet. In the case of a persistent energy‐rich Western diet, colonocyte metabolism passes from oxidative metabolism, with a high consumption of oxygen, to anabolism with a consequent decrease in oxygen consumption [42]. The lower consumption of oxygen by the colonocytes means a greater availability of oxygen for the microbiota and means another push toward gut dysbiosis. The increase in microbes capable of using oxygen is detrimental for the host, because it means that both the number of competitors for oxygen and the availability of energy for the colonic microbiota are increasing."

"The origin of the gut microbiota is environmental [2, 46]: For this reason, it is ‘seen’ by our immune system as a foreign element to be monitored to prevent it from spreading outside the intestine. Definitively, it is what is needed to keep the immune system on alert at all times."​

 

[Broken man]

Gut microbes are controlled by immune system, even "good" microbes can do damage to unhealthy people.... These gut bacteria prevent mice from becoming obese -- what could that mean for us?
Microbiome Species that Keep Mice Lean or Obese Are Balanced by Immune System

 

[TheBeard]

- The human gut microbiota is neither an organ nor a commensal

"To have a gut microbiota, it means to have available a great collection of exclusive enzymes, different from those of the host, although similar in their functions. Thus, besides to be a catabolic system [] for its additional and complementary role in digestion, the gut microbiota may be seen as a community of cells capable of cooperating in many metabolic reactions needed for the biotransformation of foreign molecules that we cannot metabolize easily enough, such as drugs, xenobiotics, polyphenols, antibiotics, and chemical food additives. To understand the metabolic importance of gut microbiota, it is enough to know that there are maybe 3000 cytochrome P450 enzymes in gut bacteria, while the correspondent CYP450 in humans are only 57 [33].

The availability of such a large number of microbial enzymes capable of modifying molecules already in the intestine, before reaching the liver, is of great importance, even if it creates problems in taking oral medications. Indeed, the presence of human gut microbiota should be taken into account during therapeutic intervention, as the microbiota can metabolize drugs and as therapy itself may affect both the metabolic activity of the gut microbiota and its composition [30].

On the other hand, the fact that the microbiota performs useful functions for the intestine and liver is not surprising, considering that both are digestive organs and that both, the hepatocytes and the intestinal epithelium have in common the same developmental origin from the ventral foregut endoderm."

- Anatomical plane - Wikipedia
- Embriology: The development of the gastrointestinal tract | Medical Animations​

"The shift of the composition of the microbiota from obligate to facultative anaerobic bacteria is another consequence of dietary changes, such as the adoption of an energy‐dense Westernized diet. In the case of a persistent energy‐rich Western diet, colonocyte metabolism passes from oxidative metabolism, with a high consumption of oxygen, to anabolism with a consequent decrease in oxygen consumption [42]. The lower consumption of oxygen by the colonocytes means a greater availability of oxygen for the microbiota and means another push toward gut dysbiosis. The increase in microbes capable of using oxygen is detrimental for the host, because it means that both the number of competitors for oxygen and the availability of energy for the colonic microbiota are increasing."

"The origin of the gut microbiota is environmental [2, 46]: For this reason, it is ‘seen’ by our immune system as a foreign element to be monitored to prevent it from spreading outside the intestine. Definitively, it is what is needed to keep the immune system on alert at all times."​

So Peat and Georgi are wrong: gut bacteria are essential.