Faecal transplants alleviated nerve pain in people with diabetes

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Wow! Never would have expected the link between gut flora and peripheral neuropathy.

Couldn’t read the whole item, but it sounds like the trial intervention was pretty small (32 people).

Will be interesting to see if further larger trials confirm the findings
 
I assume the procedure won't be the same as the Internet video involving two people and a cup?
 
There is supposed to be a close connection between the gut and the nervous system via the Vagus nerve and it is believed to be why so many people now suffer with anxiety and mental health problems, because our gut health is poor possibly due to additives/highly processed foods/not enough fibre in our diet, so it doesn't seem to be too much of a stretch to think that improving gut health can improve nerve health too. Very interesting!
 
I was thinking about you @MikeyBikey when I read this, but I am guessing the very small trial of 32 didn't include many/any amputees to give useful data. It is still a little glimmer of hope though that there might be a treatment option at some point in the future. Hopefully they will get funding for further and more extensive trials, although I think even with faecal transplants it would be necessary to change/improve diet to maintain and support the transplant.
 
The paper: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00220-6

Distal symmetric polyneuropathy (DSPN) is the most common neuropathy in patients with diabetes mellitus (DM), and it represents a pernicious unmet medical need. DSPN affects approximately half of the patients with DM, including both type 1 and type 2 DM (T1DM and T2DM).

DSPN is associated with increased mortality, lower-limb amputations, and distressing painful neuropathic symptoms, all of which have a negative impact on patients’ functionality, mood, and health-related quality of life.

Although lifestyle modification, glucose control, and a few medications may ameliorate the symptoms in some patients with DSPN, no disease-modifying treatments for DSPN are currently available due to the paucity of understanding of its underlying pathogenetic mechanism and lack of effective targets.

There is compelling and converging evidence to suggest a causative role of gut microbiota in maintaining glucose homeostasis.

In addition, the gut microbiota appears to function at the intersection of the gut-brain and the neuroimmune-endocrine axes, forming a complex network that can affect the nervous system.

An increasing number of studies have demonstrated that the crosstalk between the gut microbiota and brain may crucially impact neurodegenerative disorders of the central nervous system, such as in Parkinson’s and Alzheimer’s diseases.

Moreover, the gut microbiota and its bioactive substances are known to regulate host bioenergetics and inflammation, which may be mechanistic pathways of DSPN.

A recent study with a small sample size showed that the gut microbiota of patients with DSPN differed from that of healthy controls.

However, the causative relationship between gut microbiota and peripheral nervous system (PNS) disorders in DM remains elusive.
Fecal microbiota transplantation (FMT) has become a powerful strategy to investigate whether the gut microbiota plays a causative role in specific neurological diseases.

In our study, we found significant differences in the gut microbiota among subjects with normal glucose (NG) levels, patients with DM but not DSPN, and patients with DSPN. Furthermore, we demonstrated that the fecal microbiota from patients with DSPN induced more severe peripheral neuropathy than patients with DM but not DSPN and subjects with NG levels, as shown by inoculating the fecal microbiota into db/db mice, suggesting that dysbiosis of gut microbiota contributes to the progression of DSPN. Subsequently, we conducted an FMT from healthy donors to patients with DSPN who responded poorly to conventional treatments in a randomized, double-blind, placebo-controlled pilot clinical trial (RCT). The results show that modulation of the composition and function of gut microbiota via FMT from healthy donors induced a significant alleviation of DSPN. This study revealed a potentially causative link between gut microbiota and DSPN, which could become a therapeutic target for developing effective treatments.
 
This group are also major proponents of the fibre (and probiotics) -> better microbiome -> T2D, obesity, inflammation etc etc etc improvements. See eg (amongst a bunch of others) https://www.science.org/doi/10.1126/science.aao5774

Short-chain fatty acids (SCFAs) are produced by various human gut microbes. SCFAs act as an energy source to the colonic epithelium and are also sensed by host signaling pathways that modulate appetite and inflammation. Deficiency of gut SCFAs is associated with type 2 diabetes. Zhao et al. found that adopting a high-fiber diet promoted the growth of SCFA-producing organisms in diabetic humans. The high-fiber diet induced changes in the entire gut microbe community and correlated with elevated levels of glucagon-like peptide-1, a decline in acetylated hemoglobin levels, and improved blood-glucose regulation.

(Zhao does seem to cite himself a lot, but maybe that's just because he's a front-runner in the field.)

My guess is that he would say that lots of fibre and/or probiotics are likely to produce the same kind of results for DSPN as FMT.

FWIW, that might have been the case for me: I started to eat lots & lots of fibre after my T2D DX and my mild-to-moderate small-fibre foot neuropathy went away. But that could have been due to dealing with my metabolic syndrome via weight loss and improving circulation via exercise, independently of any change to my microbiome. Or (more likely?) all of these factors operated together in complex ways to deliver improvements.

This kind of consideration seems to be one of the reasons many experts appear to be sceptical of Zhao et al: insufficiently robust demonstrations of causality because of small sizes, unclear translations betwwen animal and human models and just extreme complexity of the underlying systems.

It's all fascinating but it's nowhere near settled science at the moment, as far as I can see.
 
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