Alzheimer’s Disease, the Microbiome, and 21st Century Medicine
David Perlmutter in The Microbiome and the Brain, 2019
Comparison of the microbiomes of patients with dementia due to Alzheimer’s disease versus age-matched controls showed a marked difference in both the complexity and distribution of microbiota, as shown by Vogt et al. (Vogt et al., 2017) and noted in this book’s chapter by Dr. Zhang. The phyla Firmicutes and Actinobacteria were reduced in patients with Alzheimer’s disease, a finding that parallels results from patients with obesity and type 2 diabetes. Within Firmicutes, the families Ruminococcaceae, Turicibacteraceae, Peptostreptococcaceae, Clostridiaceae, and Mogibacteriaceae were reduced, and within Actinobacteria, the family Bifidobacteriaceae was reduced. In contrast, members of the phylum Bacteroidetes were found to be increased in patients with Alzheimer’s disease, reflected at the family level by an increase in Bacteroidaceae and Rikenellaceae. This reduction led the authors to speculate that the insulin resistance associated with all three conditions (Alzheimer’s, obesity, and type 2 diabetes) may actually be a microbiome-driven mechanism. Furthermore, the degree of abnormality in the cerebrospinal fluid (CSF) samples from Alzheimer’s patients tended to correlate with the microbiome alterations, such that those individuals with more exaggerated microbiome changes tended to also have more severe CSF abnormalities.
Enzyme Kinetics and Drugs as Enzyme Inhibitors
Peter Grunwald in Pharmaceutical Biocatalysis, 2019
It could be recently demonstrated by Routy et al. (2018; Gustave Roussy Cancer Campus in Villejuif, France) that the question whether cancer patients respond to an anti-PD-1/PD-L1 immune therapy depends among others on the bacterial composition within the gut. Patients who received a treatment with antibiotics within a period of two months before to one month after immune therapy benefited significantly less from immune checkpoint inhibitors. Fecal microbiota transplantation from patients responding to these inhibitors to germ-free or antibiotics-treated mice ameliorated their response to an immune therapy—an effect not seen when the microbiota of non-responders was used. From metagenomics of patients stool the researchers could associate an improved clinical outcome with a surplus of the bacterium Akkermansia muciniphila. In a further publication, Vancheswaran Gopalakrishnan et al. (2017; University of Texas MD Anderson Cancer Center in Houston, Texas) discussed the results of an investigation into the gut microbiome of melanoma patients undergoing anti-PD-1/PD-L1 immune therapy. Responding patients exerted a higher diversity associated with a longer progression-free survival. The researchers also identified bacteria linked to a therapeutic success: in responding patients the abundance of the Ruminococcaceae family/faecalibacterium was high, in non-responders that of Bacteroidales. As in the above case the results were confirmed by fecal transplants to mice.
Human Gut Microbiota–Transplanted Gn Pig Models for HRV Infection
Lijuan Yuan in Vaccine Efficacy Evaluation, 2022
Szajewska et al. (2011) demonstrate that LGG improves HRV-induced diarrhea. That study used subjects one month to 18 years old but did not specify the delivery type. It is possible that LGG may not have the same protective effects on C-section-delivered infants which contain a different gut microbiota compared with vaginally delivered infants. Although all the pigs studied received the oral attenuated HRV vaccine, the protection against virulent HRV-induced diarrhea was only partial (Wen et al., 2014a). There were no significant differences in protection rate against diarrhea or virus shedding, the severity of diarrhea, or the titer of virus shedding (data not shown); therefore, we could not evaluate quantitatively whether the changes in the microbiome correlate with protection against diarrhea or virus shedding. Fifty percent (2/4) of the pigs in the –LGG+HRV group were protected from infection upon virulent HRV challenge. There are no apparent differences in the abundant taxa between protected (Gp09.06 and Gp10.09) versus unprotected (Gp10.10 and Gp10.11) pigs (Figure 11.1A, group “–LGG+HRV”). However, the low-abundance bacterial taxa (Figures 11.5 and 11.6), which accounted for less than 0.5% of the microbiota, showed that one of the two protected pigs (Gp09.06) harbored unique bacteria such as Ruminococcaceae. The other protected pig (Gp10.09) shared similar low-abundance taxa with unprotected pigs. Further studies with more animals would be needed to identify rare taxa potentially associated with viral protection.
Altered gut microbial profile is associated with abnormal metabolism activity of Autism Spectrum Disorder
Published in Gut Microbes, 2020
Zhou Dan, Xuhua Mao, Qisha Liu, Mengchen Guo, Yaoyao Zhuang, Zhi Liu, Kun Chen, Junyu Chen, Rui Xu, Junming Tang, Lianhong Qin, Bing Gu, Kangjian Liu, Chuan Su, Faming Zhang, Yankai Xia, Zhibin Hu, Xingyin Liu
The abundance of middle chain fatty acids (MCFAs) such as hexanoic acid showed increased significantly in ASD group. Zhu et al. reported that Clostridium cluster IV and Ruminococcaceae bacterium CPB6 can produce hexanoic acid.39 The Ruminococcaceae family including Faecalibacterium sp. CAG: 74, Subdoligranulum variabile, Clostridium sp. CAG: 269 and Eubacterium sp. CAG: 38 displayed a positive correlation with hexanoic acid level. Moreover, previous study found the ASD was associated with higher hexanoic acid levels in the blood in comparison to the TD group.38 Moreover, Ruminococcus lactaris is a key bacterium predicted by the NetShift method and presented as positively correlated with hexanoic acid (P < .1, Figure 5(g)). Viewed together, this information further suggested that some species from Ruminococcus family may be involved in the development of ASD diseases via hexanoic acid production. MCFAs are ligands of GPR84, which enhances the production of lipopolysaccharide-induced pro-inflammatory immune factor IL-12 P40 (P40 is the subunit of IL-12).40 It has been reported that IL-12 or IL-12 P40 is significantly increased in children with ASD.36,41 Moreover, Ashwood et al. reported that IL-12 P40 is positively correlated with lethargy and stereotypy behavior.36 Therefore, future studies focus on whether hexanoic acid produced by gut bacteria metabolism would help identify new drug targets for ASD.
The association between gut microbiome and anthropometric measurements in Bangladesh
Published in Gut Microbes, 2020
Gwendolyn Osborne, Fen Wu, Liying Yang, Dervla Kelly, Jiyuan Hu, Huilin Li, Farzana Jasmine, Muhammad G Kibriya, Faruque Parvez, Ishrat Shaheen, Golam Sarwar, Alauddin Ahmed, Mahbub Eunus, Tariqul Islam, Zhiheng Pei, Habibul Ahsan, Yu Chen
The relative abundance of the genus Acidaminococcus was higher in participants with a higher BMI, WC, and HC. This was also found in a study comparing overweight and obese individuals with normal weight individuals.29 The literature on Acidaminococcus is fairly sparse, but one characteristic of the species that has been described is their ability to use glutamate as a sole source of energy.30 Glutamate has been shown to play an important role in providing oxidative fuel for the intestinal epithelium in animal models31 and in the restoration of gut barrier function in vitro and maintenance of the gut epithelium.32 Thus, overgrowth of bacteria that can ferment glutamate may be related to an unhealthy metabolic state. The positive associations of Acidaminococcus with BMI, WC, and HC were stronger in women for some anthropometric measures in the present study, suggesting Acidaminococcus may play a more important role in adiposity in women. The Ruminococcaceae family was found to have an inverse association with MUAC, WC, and WHR. Ruminococcaceae was associated with a lower risk of weight gain in adults in another study, and was suggested to be functionally linked to a lean phenotype.33 It has also been found to be decreased in obese individuals compared to healthy individuals.34Ruminococcaceae are considered a key commensal bacterial family in the gut of healthy individuals.35 These butyrate-producing bacteria may protect healthy individuals from chronic intestinal inflammation.35
The double-edged sword of probiotic supplementation on gut microbiota structure in Helicobacter pylori management
Published in Gut Microbes, 2022
Ali Nabavi-Rad, Amir Sadeghi, Hamid Asadzadeh Aghdaei, Abbas Yadegar, Sinéad Marian Smith, Mohammad Reza Zali
A recent study conducted in China reported the advantage of multi-strain probiotic administration in which detrimental bacteria were enriched in the antibiotic group while commensal bacteria were more abundant in the probiotic group.192Lachnospiraceae UCG 006 and Eubacterium ventriosum, as commensal bacteria, can protect the human intestinal against colorectal cancer by producing SCFAs.246,247 Furthermore, Ruminococcaceae bacteria are one of the main butyrate producers in the human digestive tract; therefore, promoting the integrity of the gut barrier.248 On the other hand, the increased proportion of Leptotrichia is a risk factor for colorectal cancer;249 however, certain Leptotrichia species might be inversely correlated to pancreatic cancer.250 Moreover, Leptotrichia is reported as an oral health-related genus, substantially enriched in healthy individuals without dental caries experience.251
Related Knowledge Centers
- Clostridia
- Coccus
- Commensalism
- Obligate Anaerobe
- Bacillus
- Faecalibacterium
- Gut Microbiota
- Ruminococcus