Supplementation with Combined Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 Across Development Reveals Sex Differences in Physiological and Behavioural Effects of Western Diet in Long–Evans Rats

Abstract

The gut microbiome affects various physiological and psychological processes in animals and humans, and environmental influences profoundly impact its composition. Disorders such as anxiety, obesity, and inflammation have been associated with certain microbiome compositions, which may be modulated in early life. In 62 Long–Evans rats, we characterised the effects of lifelong Bifidobacterium longum R0175 and Lactobacillus helveticus R0052 administration—along with Western diet exposure—on later anxiety, metabolic consequences, and inflammation. We found that the probiotic formulation altered specific anxiety-like behaviours in adulthood. We further show distinct sex differences in metabolic measures. In females, probiotic treatment increased calorie intake and leptin levels without affecting body weight. In males, the probiotic seemed to mitigate the effects of Western diet on adult weight gain and calorie intake, without altering leptin levels. The greatest inflammatory response was seen in male, Western-diet-exposed, and probiotic-treated rats, which may be related to levels of specific steroid hormones in these groups. These results suggest that early-life probiotic supplementation and diet exposure can have particular implications on adult health in a sex-dependent manner, and highlight the need for further studies to examine the health outcomes of probiotic treatment in both sexes.

Ingestion of probiotic (Lactobacillus helveticus and Bifidobacterium longum) alters intestinal microbial structure and behavioral expression following social defeat stress

“…Given that we used a repeated defeat stressor and collected samples before, during, and after social stress, obtaining gut samples, such as from caecum, was not possible. Finally, there is a recent report that treatment with CEREBIOME® decreases food intake and body weight gain in male but not in female rats 57 . This suggests that, going forward, measures of food intake and body mass should be included in studies such as this one.…”

Neurobiological effects of a probiotic-supplemented diet in chronically stressed male Long-Evans rats: Evidence of enhanced resilience

“…Due to practical challenges associated with space and resources, it was only feasible to conduct the present study with one sex (i.e., males). To increase translational value, however, it is important for future investigations to include both males and females since depression is more prevalent in human females ( Albert, 2015 , Myles et al, 2020a , Myles et al, 2020b , Yang et al, 2015 ). Further, clarification of the most effective ways to administer probiotics, as well as timing and dosage, are required to more fully understand the effects of these supplements ( Myles et al, 2020a , Myles et al, 2020b ).…”

“…To increase translational value, however, it is important for future investigations to include both males and females since depression is more prevalent in human females ( Albert, 2015 , Myles et al, 2020a , Myles et al, 2020b , Yang et al, 2015 ). Further, clarification of the most effective ways to administer probiotics, as well as timing and dosage, are required to more fully understand the effects of these supplements ( Myles et al, 2020a , Myles et al, 2020b ). Tracking natural changes in the ecosystem of the microbiome following chronic unpredictable stress exposure in the absence of microbiota-targeted intervention will also contribute valuable findings to our understanding of stress-induced dysbiosis and allostatic load.…”

“…Resident macrophages of the central nervous system known as microglia represent an additional mediating mechanism between the gut microbiome and neural processes ( Wang et al, 2016 , Wang et al, 2018 ). Some probiotics have been shown to buffer proinflammatory microglial phenotypes ( Chunchai et al, 2018 ) and enhance neuroplasticity in rodents exposed to a chronic high fat diet and associated inflammation ( Buffington et al, 2016 , Myles et al, 2020a , Myles et al, 2020b ). Since disrupted neural-microglia interactions have been associated with anxiety disorders such as depression, this may represent a mechanism for the antidepressive effect of some probiotics ( Wohleb, 2016 ).…”

Young at Gut—Turning Back the Clock with the Gut Microbiome

“…Precision medicine offers one avenue to provide better management of care with the great individual variability in genes, environment, and lifestyle that can influence the outcome of many of the interventions that we touched upon in this review. For example, CR [ 159 ] and probiotics [ 185 ] can be impacted by sex and diet [ 186 ], and metformin [ 187 ] can be impacted by genetic differences. Precision medicine, and especially precision medicine involving the microbiome, is still a nascent field, but further development of the field would help in the treatment of age-related disease.…”