Terapia personalizada com consórcio de bactérias fecais para o tratamento da obesidade
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2022-12-16
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Universidade Estadual Paulista (Unesp)
Resumo
RESUMO: A ingestão de probióticos tem sido utilizada para modificar de forma benéfica a microbiota intestinal de indivíduos portadores de algumas doenças crônicas. Entretanto, essa abordagem apresenta resultados discrepantes e limitações, relacionados à resiliência da microbiota intestinal e à individualidade genética do paciente, que parecem interferir na efetividade dos probióticos. Objetivo: avaliar o efeito da terapia personalizada com consórcio de bactérias fecais na redução do risco da obesidade e suas consequências em modelo animal. Métodos: as cepas para o tratamento personalizado foram previamente isoladas de material fecal de crianças e armazenadas em um banco de células. O estudo foi conduzido com camundongos Swiss, livres de patógenos específicos, distribuídos aleatoriamente em quatro grupos: Controle (C) (n=10), Obeso (OB) (n=10), Obeso + Probiótico Personalizado (OPP) (n=15), Obeso + Cepas Compartilhadas (OCC) (n=13). Inicialmente, os animais receberam um coquetel de antibióticos para depletar a microbiota intestinal e, posteriormente, foram recolonizados com a microbiota fecal dos doadores das cepas personalizadas, via transplante de microbiota fecal. A obesidade foi induzida por dieta hiperlipídica e o estudo teve duração de 120 dias. As cepas previamente isoladas e armazenadas no banco de células foram utilizadas para o tratamento dos animais dos grupos OPP e OCC (8 log UFC/dia), a partir do T85. A evolução da obesidade foi avaliada pela variação ponderal, coeficiente de eficácia alimentar, perfil lipídico e de citocinas, área e diâmetro dos adipócitos e análise da composição da microbiota fecal. Resultados: A depleção da microbiota intestinal causou perda de peso acentuada (p<0,05) e o transplante de microbiota fecal foi capaz de reverter o quadro de emagrecimento, levando à recuperação do peso corporal (p>0,05). A partir da sétima semana do estudo (T71), os animais induzidos à obesidade exibiram ganho de peso superior ao do controle, alimentado com dieta convencional e os animais que receberam as cepas personalizadas (OPP) apresentaram variação ponderal semelhante ao do controle (C) na terceira semana de tratamento (T99 e T106). A ingestão das cepas personalizadas também melhorou o perfil lipídico dos animais, que exibiram níveis de não HDLc semelhantes aos dos animais não induzidos à obesidade (p>0,05). A análise histológica evidenciou que o tratamento com as cepas personalizadas minimizou o aumento da área e diâmetro dos adipócitos (p<0,05), reestabeleceu o equilíbrio entre os filos Firmicutes e Bacteroidetes e aumentou a proporção de Akkermansia spp. Conclusão: A recolonização da microbiota intestinal com o uso do transplante de microbiota fecal reverteu a disbiose intestinal, o prolapso retal e a perda de peso observada após o uso de antibióticos. A administração das cepas personalizadas durante cinco semanas sugeriu efeito benéfico no controle do ganho de peso na terceira semana de tratamento e melhorou o perfil lipídico dos animais. Além disso, o tratamento personalizado foi capaz de modular beneficamente a microbiota intestinal e minimizar a hipertrofia do tecido adiposo branco epididimal, sinalizando para seu potencial uso no controle da obesidade.
ABSTRACT: The intake of probiotics has been used to beneficially modify the intestinal microbiota of individuals with some chronic diseases. However, this approach presents discrepant results and limitations, related to the resilience of the intestinal microbiota and the genetic individuality of the patient, which seem to interfere in the effectiveness of probiotics. Aim: evaluate the effect of personalized therapy with fecal bacteria consortium in reducing the risk of obesity and its consequences in animal model. Methods: the strains for personalized treatment were previously isolated from children's fecal material and stored in a cell bank. The study was conducted with Swiss mice, specific pathogen free, randomly distributed into four groups: Control (C) (n=10); Obese (OB) (n=10); Obese + Personalized Probiotic (OPP) (n=15), Obese + Shared Strains (OCC) (n=13). Initially, the animals received a cocktail of antibiotics to deplete the intestinal microbiota and were subsequently recolonized with the donor fecal microbiota of the customized strains, via fecal microbiota transplantation. Obesity was induced by a high-fat diet and the study lasted 120 days. The strains previously isolated and stored in the cell bank were used for the treatment of animals from groups OPP and OCC (8 log CFU/day), from T85. The evolution of obesity was evaluated by weight variation, coefficient of food efficacy, lipid and cytokine profile, area and diameter of adipocytes and analysis of fecal microbiota composition. Results: The depletion of the intestinal microbiota caused marked weight loss (p<0.05) and fecal microbiota transplantation was able to reverse the weight loss, leading to recovery of body weight (p>0.05). From the seventh week of the study (T71), the animals induced to obesity exhibited weight gain higher than the control, fed with conventional diet and the animals that received the personalized strains (OPP) presented weight variation similar to the control (C) in the third week of treatment (T99 and T106). The intake of the personalized strains also improved the lipid profile of the animals, which exhibited non-HDLc levels similar to those animals not induced to obesity (p>0.05). Histological analysis showed that treatment with customized strains minimized the increase in adipocytes area and diameter (p<0.05), reestablished the balance between Firmicutes and Bacteroidetes and increased the proportion of Akkermansia spp. Conclusion: The recolonization of the intestinal microbiota with the use of fecal microbiota transplantation reversed intestinal dysbiosis, rectal prolapse and weight loss observed after antibiotic use. The administration of customized strains for five weeks suggested a beneficial effect on weight gain control in the third week of treatment and improved the lipid profile of the animals. In addition, the personalized treatment was able to beneficially modulate the intestinal microbiota and minimize hypertrophy of epididymal white adipose tissue, signaling its potential use in the control of obesity.
ABSTRACT: The intake of probiotics has been used to beneficially modify the intestinal microbiota of individuals with some chronic diseases. However, this approach presents discrepant results and limitations, related to the resilience of the intestinal microbiota and the genetic individuality of the patient, which seem to interfere in the effectiveness of probiotics. Aim: evaluate the effect of personalized therapy with fecal bacteria consortium in reducing the risk of obesity and its consequences in animal model. Methods: the strains for personalized treatment were previously isolated from children's fecal material and stored in a cell bank. The study was conducted with Swiss mice, specific pathogen free, randomly distributed into four groups: Control (C) (n=10); Obese (OB) (n=10); Obese + Personalized Probiotic (OPP) (n=15), Obese + Shared Strains (OCC) (n=13). Initially, the animals received a cocktail of antibiotics to deplete the intestinal microbiota and were subsequently recolonized with the donor fecal microbiota of the customized strains, via fecal microbiota transplantation. Obesity was induced by a high-fat diet and the study lasted 120 days. The strains previously isolated and stored in the cell bank were used for the treatment of animals from groups OPP and OCC (8 log CFU/day), from T85. The evolution of obesity was evaluated by weight variation, coefficient of food efficacy, lipid and cytokine profile, area and diameter of adipocytes and analysis of fecal microbiota composition. Results: The depletion of the intestinal microbiota caused marked weight loss (p<0.05) and fecal microbiota transplantation was able to reverse the weight loss, leading to recovery of body weight (p>0.05). From the seventh week of the study (T71), the animals induced to obesity exhibited weight gain higher than the control, fed with conventional diet and the animals that received the personalized strains (OPP) presented weight variation similar to the control (C) in the third week of treatment (T99 and T106). The intake of the personalized strains also improved the lipid profile of the animals, which exhibited non-HDLc levels similar to those animals not induced to obesity (p>0.05). Histological analysis showed that treatment with customized strains minimized the increase in adipocytes area and diameter (p<0.05), reestablished the balance between Firmicutes and Bacteroidetes and increased the proportion of Akkermansia spp. Conclusion: The recolonization of the intestinal microbiota with the use of fecal microbiota transplantation reversed intestinal dysbiosis, rectal prolapse and weight loss observed after antibiotic use. The administration of customized strains for five weeks suggested a beneficial effect on weight gain control in the third week of treatment and improved the lipid profile of the animals. In addition, the personalized treatment was able to beneficially modulate the intestinal microbiota and minimize hypertrophy of epididymal white adipose tissue, signaling its potential use in the control of obesity.
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Palavras-chave
Obesidade, Probiótico personalizado, Microbiota intestinal, Antibiótico, Transplante de microbiota fecal