how the microbiota is used in the treatment of degenerative diseases – WWN

how the microbiota is used in the treatment of degenerative diseases – WWN

Of Cesare Peccarisi

Altered populations of bacteria are being studied, each related to a specific disease and in the meantime therapies based on microbiota transplantation are being tried with mixed success

No one is ever alone even in the most remote mountain hut. We never think about it, but from birth we are always in the company of a symbiotic super-organism partly inherited from our mother and partly acquired over the years from the environment. It weighs as much as our brain and communicates continuously with it, forming the so-called gut-brain axis, a real entero-cerebral connectome called «gut brain» composed of the microbial populations that live in the intestine and which exercises continuous control over brain functions and dysfunctions.

Pre, probiotics and transplant

This connection promises to become a valuable therapeutic target for various neuro-psychic diseases such as that of Parkinson or the depression because by acting on the intestinal microbiota with pre- and probiotics it is possible to improve them.
For about ten years another treatment has proven to be decisive for serious intestinal dysbiosis such as Clostridium difficile where there was no antibiotic or diet that worked: this is the transplant of microbiota
from healthy subjects that effectively repopulates the intestinal flora of patients with antibiotic resistance who in the most serious cases, especially if hospitalized elderly people, even risked death from very serious colitis and devastating and incurable diarrhea.

Double edged weapon

And if the restoration of dysbiosis also benefits the conditions at the other end of the gut-brain axis, the opposite can also happen and this further confirms this bidirectional relationship. A study just published on Brain by a group of Italian, Irish and English researchers directed by Yvonne Nolan of the University of Cork demonstrated that by transplanting the microbiota of subjects with Alzheimer’s disease into healthy subjects, they too become ill, while using microbiota from healthy subjects of the same age this does not happen. Obviously the transplantation of the microbiota of the 69 Alzheimer’s patients from the IRCCS Centro San Giovanni di Dio Fatebenefratelli of Brescia used for the study was not done on other men, but on mice, because, even if there is not yet proof of an effect opposite of transmitting the disease, it was better not to risk inducing it in those who were well.

Long way to go

«Given the results, it was better this way because the hippocampus of the previously healthy mice underwent disturbances in neurogenesis, i.e. neuronal plasticity, with consequent alterations in memory and behavior similar to those of the patients from whom the fecal sample came – says Professor Alessandro Padovani of the University of Brescia and president of the Italian Society of Neurology -. It wasn’t just their microbiome that changed, but also the metabolome, both intestinal and cerebral”. By metabolome we mean the set of metabolites, i.e substances involved in cellular metabolic processes such as hormones, neurotransmitters etc.

Headaches, depression and psychosis

The microbiome is a complex and dynamic ecosystem, and understanding its role in host disease and its potential for treating various disorders associated with its alterations will require further studies.
However, there is already a lot of data collected so far: in the headaches for example, an excess of Caenorhabditis elegans bacteria is observed in the depression Eggerthella, Atopobium and Bifidobacterium abound, a little less Faecalibacterium, in psychosis and bipolar disorder
Saccharomyces cerevisiae and Candida albicans. The sleep it gets worse if bifidobacteria decrease in the microbiota, but according to a study published in Journal of Experimental Neurology from the University of Missouri by rebalancing the intestinal flora it is also possible to improve morpheic apnea, other sleep disorder with altered microbiota.

Two years ago Colorado University indicated on Frontiers of Behavioral Neurosciences than the probiotic Lactobacillus rhamnosus can improve REM sleep that of dreams, thanks to an increased production of short-chain fatty acids such as butyric acid, effective on the genes responsible for controlling sleep-wake rhythms.

Microbiota and Parkinson’s disease

The correlations between the microbiota and Parkinson’s disease were among the first to be studied: already in 2004 Heiko Braak of the Goethe University of Frankfurt indicated that this disease is a especially intestinal departure where the formation of alpha-synuclein occurs, the altered protein marker of the disease which, propagating from the intestine to the brain along the vagus nerve, converts the other normal proteins into toxic microclusters with a domino effect. The formation of alpha-synuclein in the microbiota would be favored by the lack of lactobacilli and in particular in Parkinson’s patients the bacteria Faecalibacterium, Roseburia and Prevotella appear reduced, while Bifidobacterium and Lactobacillus are increased, even if some think that these alterations are partly attributable to chronic therapies of these patients.

In Alzheimer’s disease

In Alzheimer’s disease, Phylum Bacteroidetes are especially abundant and, to a lesser extent, Phylum Firmicutes and Verrucomicrobiota. The latest Brain study from which we started highlighted a significant increase in Desulfovibrio and a significant reduction in Clostridium and Coprococci producing short-chain fatty acids, notoriously associated with healthy aging. Incidentally, the researchers found no significant gender differences in the microbiota of male and female Alzheimer’s patients.

A bit of history

The National Institutes of Health (NIH USA) had already understood the extent of the gut-brain connections for some time, so much so that from 2007 to 2016 they activated the Human Microbiome Project (HMP, acronym for human microbiome project) from which many studies like this were born which increasingly demonstrate how altered compositions of the intestinal microbiota correlate with multiple diseases. Incidentally, the intestinal microbiota is the largest component of the microbiome that includes them all: skin, scalp, vaginal, uterine microbiota, etc. etc. Almost twenty years after the launch of the HMP project, we are now trying to exploit the potential of the microbiome by looking at manipulation of its microbial populations as a new therapeutic modality that is increasingly accessible with the development of precision therapies that exploit intestinal microbial processes.

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November 18, 2023 (changed November 18, 2023 | 6:50 pm)

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