Probiotic

Probiotics are live microorganisms promoted with claims that they provide health benefits when consumed, generally by improving or restoring the gut microbiota. Probiotics are considered generally safe to consume, but may cause bacteria-host interactions and unwanted side effects in rare cases. There is some evidence that probiotics are beneficial for some conditions, but there is little evidence for many of the health benefits claimed for them. The first discovered probiotic was a certain strain of bacillus in Bulgarian yoghurt, called Lactobacillus bulgaricus. The discovery was made in 1905 by Bulgarian physician and microbiologist Stamen Grigorov. The modern-day theory is generally attributed to Russian Nobel laureate Élie Metchnikoff, who postulated around 1907 that yoghurt-consuming Bulgarian peasants lived longer. A growing probiotics market has led to the need for stricter requirements for scientific substantiation of putative benefits conferred by microorgani

Development and applications of hyperpolarized 13C and 1H MR spectroscopy of cerebral metabolism at ultra-high field

Emmanuelle Ines Flatt

This thesis is composed of four studies centered on investigating cerebral metabolism using magnetic resonance spectroscopy (MRS) of hyperpolarized and non-hyperpolarized compounds at ultra-high field. In the first two chapters, we studied longitudinally the effects of different treatments for hepatic encephalopathy (HE) on the neurometabolic changes associated with chronic HE using a rat model of type C HE and a multimodal approach including 1H MRS. The effects of the antibiotic rifaximin administered at different doses as well as its combination with probiotics were studied in the established model of bile duct ligated (BDL) rats. We showed for the first time the beneficial effects of the combined rifaximin and the probiotic Vivomixx® on the neurometabolic changes in vivo and longitudinally in a rat model of type C HE. The longitudinal changes of some brain metabolites concentration (glutamine, glutamate, creatine), as well as gut bifidobacteria concentration, were significantly less pronounced in the group of rats treated with rifaximin and probiotics compared to non-treated rats. We also showed that rifaximin treatment alone had limited efficacy. When administered at human dose in rats, its effects appeared only at the early stages of the disease, whereas at a higher dose some neurometabolic changes associated with HE were attenuated but the general condition of the rats was worse. In the third study, we used dissolution dynamic nuclear polarization (DNP) to hyperpolarize [2H7, U-13C6]-D-glucose, which enabled us to monitor real-time glycolysis in the healthy mouse brain. Given that glucose metabolism is tightly linked to neuronal activity, we first investigated how the change in anesthesia impacts the cerebral metabolism of hyperpolarized glucose. Anesthetics are known to influence brain activity, and in this study we showed for the first time that switching from isoflurane anesthesia to a combination of lower doses of isoflurane and medetomidine had a high impact on cerebral glucose uptake and glycolytic flow, as reflected by the increased labelling of downstream [1-13C] lactate. The second part of this study aimed at evaluating the feasibility of quantifying cerebral glucose metabolism kinetics by evaluating two different mathematical models, where kinetic rate constants were determined by fitting the models on 13C curves by non-linear regression using the Levenberg-Marquardt algorithm. We showed that a 3-compartment model is more stable and reliable than a 4-compartment model. Finally, since lithium salts are widely used for treating bipolar disorder but its mechanism of action is still not clearly understood, we evaluated the potential of hyperpolarized 6Li injected at pharmacological doses to assess its real-time bio-distribution and pharmacokinetic in the rat brain. We demonstrated first that hyperpolarized 6Li can be detected at pharmacological concentration in the rat head with high signal-to-noise ratio (SNR). We also showed that the transport of lithium through the intact blood-brain barrier brain is a limiting factor and demonstrated a striking difference between apparent 6Li T1 values in a brain with normal or disrupted blood-brain barrier.

EPFL2021

Probiotics improve the neurometabolic profile of rats with chronic cholestatic liver disease

Cristina Ramona Cudalbu, Emmanuelle Ines Flatt, Jocelin Grosse, Veronika Rackayová

Chronic liver disease leads to neuropsychiatric complications called hepatic encephalopathy (HE). Current treatments have some limitations in their efficacy and tolerability, emphasizing the need for alternative therapies. Modulation of gut bacterial flora using probiotics is emerging as a therapeutic alternative. However, knowledge about how probiotics influence brain metabolite changes during HE is missing. In the present study, we combined the advantages of ultra-high field in vivo H-1 MRS with behavioural tests to analyse whether a long-term treatment with a multistrain probiotic mixture (VIVOMIXX) in a rat model of type C HE had a positive effect on behaviour and neurometabolic changes. We showed that the prophylactic administration of this probiotic formulation led to an increase in gut Bifidobacteria and attenuated changes in locomotor activity and neurometabolic profile in a rat model of type C HE. Both the performance in behavioural tests and the neurometabolic profile of BDL+probiotic rats were improved compared to the BDL group at week 8 post-BDL. They displayed a significantly lesser increase in brain Gln, a milder decrease in brain mIns and a smaller decrease in neurotransmitter Glu than untreated animals. The clinical implications of these findings are potentially far-reaching given that probiotics are generally safe and well-tolerated by patients.

2021

Development and applications of hyperpolarized 13C and 1H MR spectroscopy of cerebral metabolism at ultra-high field

Emmanuelle Ines Flatt

EPFL2021

Development and applications of hyperpolarized 13C and 1H MR spectroscopy of cerebral metabolism at ultra-high field

Probiotics improve the neurometabolic profile of rats with chronic cholestatic liver disease

Probiotics Combined With Rifaximin for the Treatment of Chronic Hepatic Encephalopathy: A Longitudinal In Vivo 1H-MRS Study of Brain Metabolism Using BDL Rats

Development and applications of hyperpolarized 13C and 1H MR spectroscopy of cerebral metabolism at ultra-high field

Probiotics Combined With Rifaximin for the Treatment of Chronic Hepatic Encephalopathy: A Longitudinal In Vivo 1H-MRS Study of Brain Metabolism Using BDL Rats

Probiotics improve the neurometabolic profile of rats with chronic cholestatic liver disease